Wang, Dai; Schultz, Tim; Novak, Gerald P; Baker, Susan; Bennett, David A; Narayan, Vaibhav A
2018-01-01
Therapeutic research on Alzheimer's disease (AD) has moved to intercepting the disease at the preclinical phase. Most drugs in late development have focused on the amyloid hypothesis. To understand the magnitude of amyloid-related functional decline and to identify the functional domains sensitive to decline in a preclinical AD population. Data were from the Religious Orders Study and the Rush Memory and Aging Project. Cognitive decline was measured by a modified version of the Alzheimer's Disease Cooperative Study Preclinical Alzheimer Cognitive Composite. The trajectories of functional decline, as measured by the instrumental and basic activities of daily living, were longitudinally modeled in 484 participants without cognitive impairment at baseline and having both a final clinical and a postmortem neuropathology assessment of AD. Individuals with different final clinical diagnoses had different trajectories of cognitive and functional decline. Individuals with AD dementia, minor cognitive impairment, and no cognitive impairment had the most, intermediate, and least declines. While individuals with pathologic AD had significantly more cognitive decline over time than those without, the magnitude of difference in functional decline between these two groups was small. Functional domains such as handling finance and handling medications were more sensitive to decline. Demonstrating the functional benefit of an amyloid-targeting drug represents a significant challenge as elderly people experience functional decline due to a wide range of reasons with limited manifestation attributable to AD neuropathology. More sensitive functional scales focusing on the functional domains sensitive to decline in preclinical AD are needed.
Chen, Yuling; Ding, Shu; Tao, Xiangjun; Feng, Xinwei; Lu, Sai; Shen, Yuzhi; Wu, Ying; An, Xiangguang
2017-10-01
Postoperative delirium (POD) and declined cognitive function were common in patients (especially elderly patients) who underwent coronary artery bypass grafting (CABG), which may affect quality of life (QoL). The aim of this study was to determine the relationships among age, POD, declined cognitive function, and QoL in patients who underwent CABG. Consecutive patients who underwent first time elective CABG and assessed for POD using Confusion Assessment Method for intensive care unit for 5 postoperative days from November 2013 to March 2015 were recruited. A cross-sectional study was conducted during April 2015 to assess their cognitive function and QoL, using the Telephone Interview for Cognitive Status Scale and Medical Outcomes Study 36-Item Short Form Health Survey. The relationships among age, POD, declined cognitive function, and QoL were tested using path analysis. Declined cognitive function was associated with poorer QoL. POD was associated with declined cognitive function but was not associated with poorer QoL. Ageing was not associated with QoL but was associated with POD and declined cognitive function. The QoL of patients developed delirium after CABG is determined by cognitive function after discharge. Necessary strategies should be implemented to prevent POD and declined cognitive function, especially in elderly patients. © 2017 John Wiley & Sons Australia, Ltd.
Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.
Nooyens, Astrid C J; Bueno-de-Mesquita, H Bas; van Gelder, Boukje M; van Boxtel, Martin P J; Verschuren, W M Monique
2014-02-01
Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline (1995-2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.
Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.
Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard
2015-01-01
The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.
López Torres, Isabel; Torres-Sánchez, Irene; Martín Salvador, Adelina; Ortiz Rubio, Araceli; Rodríguez Alzueta, Elisabeth; Valenza, Marie Carmen
2014-11-01
Chronic obstructive pulmonary disease (COPD) is a progressive disease with a prevalence that increases with the aging of the subject. It presents a high prevalence of comorbidities, such as cognitive decline, which is gaining great clinical relevance in recent years. Factors such as pulmonary function, hypoxemia, hypercapnia or exacerbations contribute to the decline of cognitive functions. The nutritional status has been added to these factors as contributing to cognitive function decline when presenting in COPD. To evidence the relationship between cognitive decline, nutritional status and the clinical profile of patients admitted because of an acute exacerbation of COPD (AECOPD). 110 subjects hospitalized because of COPD, divided in two groups according to their nutritional status and assessment of cognitive decline at admittance, nutritional status and clinical profile. Significant differences between groups concerning nutritional status in anthropometric variables (sex and IMC), functional ability (Barthel index and Daily Life Activities Scale), quality of life (Euroqol- 5D y SGRQ), sleep quality (Pittsburgh), mood (HAD) and cognitive decline (MoCa attention, MoCa abstraction). (p<0.05). Cognitive function is affected in COPD patients with an altered nutritional status when compared to those with a normal nutritional status. The nutritional decline is a factor contributing to the impairment of cognitive functions in this kind of patients, particularly a decline in attention and abstraction ability. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
Metabolic Syndrome and 16-year Cognitive Decline in Community-Dwelling Older Adults
McEvoy, Linda K.; Laughlin, Gail A.; Barrett-Connor, Elizabeth; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Der-Martirosian, Claudia; von Mühlen, Denise
2012-01-01
PURPOSE To determine whether metabolic syndrome is associated with accelerated cognitive decline in community-dwelling older adults. METHODS Longitudinal study of 993 adults (mean 66.8 ± 8.7 years) from the Rancho Bernardo Study. Metabolic syndrome components, defined by 2001 NCEP-ATP III criteria, were measured in 1984–87. Cognitive function was first assessed in 1988–92. Cognitive assessments were repeated approximately every four years, for a maximum 16-year follow-up. Mixed-effects models examined longitudinal rate of cognitive decline by metabolic syndrome status, controlling for factors plausibly associated with cognitive function (diabetes, inflammation). RESULTS Metabolic syndrome was more common in men than women (14% vs. 9%, p=0.01). In women, metabolic syndrome was associated with greater executive function and long term memory decline. These associations did not differ by inflammatory biomarker levels. Diabetes did not alter the association of metabolic syndrome with long-term recall but modified the association with executive function: metabolic syndrome was associated with accelerated executive function decline in diabetic women only. Metabolic syndrome was not related to rate of decline on any cognitive measure in men. CONCLUSIONS Metabolic syndrome was a risk factor for accelerated cognitive decline, but only in women. Prevention of metabolic syndrome may aid in maintenance of cognitive function with age. PMID:22285865
Tolea, Magdalena I; Morris, John C; Galvin, James E
2015-01-01
To assess the directionality of the association between physical and cognitive decline in later life, we compared patterns of decline in performance across groups defined by baseline presence of cognitive and/or physical impairment [none (n = 217); physical only (n = 169); cognitive only (n = 158), or both (n = 220)] in a large sample of participants in a cognitive aging study at the Knight Alzheimer's Disease Research Center at Washington University in St. Louis who were followed for up to 8 years (3,079 observations). Rates of decline reached 20% for physical performance and varied across cognitive tests (global, memory, speed, executive function, and visuospatial skills). We found that physical decline was better predicted by baseline cognitive impairment (slope = -1.22, p<0.001), with baseline physical impairment not contributing to further decline in physical performance (slope = -0.25, p = 0.294). In turn, baseline physical impairment was only marginally associated with rate of cognitive decline across various cognitive domains. The cognitive-functional association is likely to operate in the direction of cognitive impairment to physical decline although physical impairment may also play a role in cognitive decline/dementia. Interventions to prevent further functional decline and development of disability and complete dependence may benefit if targeted to individuals with cognitive impairment who are at increased risk.
Li, He; Lv, Chenlong; Zhang, Ting; Chen, Kewei; Chen, Chuansheng; Gai, Guozhong; Hu, Liangping; Wang, Yongyan; Zhang, Zhanjun
2014-01-01
With a longer life expectancy and an increased prevalence of neurodegenerative diseases, investigations on trajectories of cognitive aging have become exciting and promising. This study aimed to estimate the patterns of age-related cognitive decline and the potential associated factors of cognitive function in community-dwelling residents of Beijing, China. In this study, 1248 older adults aged 52-88 years [including 175 mild cognitive impairment (MCI) subjects] completed a battery of neuropsychological scales. The personal information, including demographic information, medical history, eating habits, lifestyle regularity and leisure activities, was also collected. All cognitive function exhibited an agerelated decline in normal volunteers. Piece-wise linear fitting results suggested that performance on the Auditory Verbal Learning Test remained stable until 58 years of age and continued to decline thereafter. The decline in processing speed and executive function began during the early 50's. Scores on visual-spatial and language tests declined after 66 years of age. The decline stage of the general mental status ranged from 63 to 70 years of age. However, the MCI group did not exhibit an obvious age-related decline in most cognitive tests. Multivariate linear regression analyses indicated that education, gender, leisure activities, diabetes and eating habits were associated with cognitive abilities. These results indicated various trajectories of age-related decline across multiple cognitive domains. We also found different patterns of agerelated cognitive decline between MCI and normal elderly. These findings could help improve the guidance of cognitive intervention program and have implications for public policy issues.
Zaninotto, Paola; Batty, G David; Allerhand, Michael; Deary, Ian J
2018-04-24
Maintaining cognitive function is an important aspect of healthy ageing. In this study, we examined age trajectories of cognitive decline in a large nationally representative sample of older people in England. We explored the factors that influence such decline and whether these differed by gender. Latent growth curve modelling was used to explore age-specific changes, and influences on them, in an 8-year period in memory, executive function, processing speed and global cognitive function among 10 626 participants in the English Longitudinal Study of Ageing. We run gender-specific models with the following exposures: age, education, wealth, childhood socioeconomic status, cardiovascular disease, diabetes, physical function, body mass index, physical activity, alcohol, smoking, depression and dementia. After adjustment, women had significantly less decline than men in memory (0.011, SE 0.006), executive function (0.012, SE 0.006) and global cognitive function (0.016, SE 0.004). Increasing age and dementia predicted faster rates of decline in all cognitive function domains. Depression and alcohol consumption predicted decline in some cognitive function domains in men only. Poor physical function, physical inactivity and smoking were associated with faster rates of decline in specific cognitive domains in both men and women. For example, relative to study members who were physically active, the sedentary experienced greater declines in memory (women -0.018, SE 0.009) and global cognitive function (men -0.015, SE 0.007 and women -0.016, SE 0.007). The potential determinants of cognitive decline identified in this study, in particular modifiable risk factors, should be tested in the context of randomised controlled trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Reas, Emilie T; Laughlin, Gail A; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth; McEvoy, Linda K
2017-08-01
This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up. Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up. Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects. Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test. Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Nooyens, Astrid C J; van Gelder, Boukje M; Bueno-de-Mesquita, H Bas; van Boxtel, Martin P J; Verschuren, W M Monique
2018-06-01
To get insight in the impact of fish and fat intake in the prevention of accelerated cognitive decline with ageing, we tested associations between fish and different fat intakes and 5-year change in cognitive functions. In 2612 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline, dietary intake (including fish consumption) and cognitive function were assessed at baseline and at 5-year follow-up. Average fish consumption (frequency) and intakes (as energy percentages) of total fat, saturated, mono unsaturated, and polyunsaturated fatty acids (PUFA), linoleic, docosahexaenoic, eicosapentaenoic, and a-linolenic acid (ALA), and cholesterol were averaged over baseline and follow-up. Intakes were studied in relation to 5-year change in global cognitive function, memory, information processing speed, and cognitive flexibility, using ANCOVA and multivariate linear regression analyses. No consistent association between (fatty) fish consumption and cognitive decline was observed. Higher cholesterol intake was associated with faster cognitive decline (p < 0.05). Higher n-3 PUFA (especially ALA) intake was associated with slower decline in global cognitive function and memory (p < 0.01). Intakes of other fatty acids were not associated with cognitive decline. Higher cholesterol intake was detrimental, while higher ALA intake was beneficial for maintaining cognitive function with ageing, already at middle age.
The impact of retirement on age related cognitive decline - a systematic review.
Meng, Annette; Nexø, Mette Andersen; Borg, Vilhelm
2017-07-21
Knowledge on factors affecting the rate of cognitive decline and how to maintain cognitive functioning in old age becomes increasingly relevant. The purpose of the current study was to systematically review the evidence for the impact of retirement on cognitive functioning and on age related cognitive decline. We conducted a systematic literature review, following the principles of the PRISMA statement, of longitudinal studies on the association between retirement and cognition. Only seven studies fulfilled the inclusion criteria. We found weak evidence that retirement accelerates the rate of cognitive decline in crystallised abilities, but only for individuals retiring from jobs high in complexity with people. The evidence of the impact of retirement on the rate of decline in fluid cognitive abilities is conflicting. The review revealed a major knowledge gap in regards to the impact of retirement on cognitive decline. More knowledge on the association between retirement and age related cognitive decline as well as knowledge on the mechanisms behind these associations is needed.
Cognitive Aging Research: What Does It Say about Cognition? Aging?
ERIC Educational Resources Information Center
Glucksberg, Sam
Cognitive aging research needs to clarify whether or not there are functional or ability declines with aging and, if so, to understand and mediate these declines. Recent research which has demonstrated declines in cognitive functioning with age has involved episodic memory and rehearsal-independent forms of such memory. It is not known how much of…
MacDonald, Stuart W S; Keller, Connor J C; Brewster, Paul W H; Dixon, Roger A
2018-05-01
This study examines the relative utility of a particular class of noninvasive functional biomarkers-sensory functions-for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether (a) olfactory function, vision, and audition exhibited significant longitudinal declines in nondemented older adults; (b) multiwave change for these sensory function indicators predicted risk of mild cognitive impairment (MCI); and (c) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. A longitudinal sample (n = 408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively, single-assessment MCI, and multiple-assessment MCI. We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multistep screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
MacDonald, Stuart W.S.; Keller, Connor J.C.; Brewster, Paul W.H.; Dixon, Roger A.
2017-01-01
Objective This study examines the relative utility of a particular class of non-invasive functional biomarkers -- sensory functions -- for detecting those at risk of cognitive decline and impairment. Three central research objectives were examined including whether: (1) olfactory function, vision, and audition exhibited significant longitudinal declines in non-demented older adults, (2) multi-wave change for these sensory function indicators predicted risk of mild cognitive impairment, and (3) change within persons for each sensory measure shared dynamic time-varying associations with within-person change in cognitive functioning. Method A longitudinal sample (n=408) from the Victoria Longitudinal Study was assembled. Three cognitive status subgroups were identified: not impaired cognitively (NIC), single assessment mild cognitive impairment (SA-MCI), and multiple assessment mild cognitive impairment (MA-MCI). Results We tested independent predictive associations, contrasting change in sensory function as predictors of cognitive decline and impairment, utilizing both linear mixed models and logistic regression analysis. Olfaction and, to a lesser extent, vision were identified as the most robust predictors of cognitive status and decline; audition showed little predictive influence. Conclusions These findings underscore the potential utility of deficits in olfactory function, in particular, as an early marker of age- and pathology-related cognitive decline. Functional biomarkers may represent potential candidates for use in the early stages of a multi-step screening approach for detecting those at risk of cognitive impairment, as well as for targeted intervention. PMID:29809033
Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm
2016-01-01
According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844
Dong, XinQi; Simon, Melissa A; Wilson, Robert S; Mendes de Leon, Carlos F; Rajan, K Bharat; Evans, Denis A
2010-12-01
To examine the longitudinal association between decline in cognitive function and risk of elder self-neglect in a community-dwelling population. Prospective population-based study. Geographically defined community in Chicago. Community-dwelling subjects reported to the social services agency from 1993 to 2005 for self-neglect who also participated in the Chicago Health Aging Project (CHAP). Of the 5,519 participants in CHAP, 1,017 were reported to social services agency for suspected elder self-neglect from 1993 to 2005. Social services agency identified reported elder self-neglect. The primary predictor was decline in cognitive function assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Executive Function), and immediate and delayed recall of the East Boston Memory Test (Episodic Memory). An index of global cognitive function scores was derived by averaging z-scores of all tests. Outcome of interest was elder self-neglect. Logistic and linear regression models were used to assess these longitudinal associations. After adjusting for potential confounding factors, decline in global cognitive function, MMSE score, and episodic memory were not independently associated with greater risk of reported and confirmed elder self-neglect. Decline in executive function was associated with greater risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with greater risk of greater self-neglect severity (parameter estimate=0.76, standard error=0.31, P=.01). Decline in executive function was associated with risk of reported and confirmed elder self-neglect. Decline in global cognitive function was associated with risk of greater self-neglect severity. © 2010, Copyright the Authors. Journal compilation © 2010, The American Geriatrics Society.
Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology.
Insel, Philip S; Mattsson, Niklas; Mackin, R Scott; Schöll, Michael; Nosheny, Rachel L; Tosun, Duygu; Donohue, Michael C; Aisen, Paul S; Jagust, William J; Weiner, Michael W
2016-05-17
To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. © 2016 American Academy of Neurology.
Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology
Mattsson, Niklas; Mackin, R. Scott; Schöll, Michael; Nosheny, Rachel L.; Tosun, Duygu; Donohue, Michael C.; Aisen, Paul S.; Jagust, William J.; Weiner, Michael W.
2016-01-01
Objective: To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. PMID:27164667
Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology
DOE Office of Scientific and Technical Information (OSTI.GOV)
Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott
Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less
Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology
Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott; ...
2016-04-15
Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ 42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloidmore » positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ 42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less
Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm
2016-07-01
According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Epperly, Ted; Dunay, Megan A; Boice, Jack L
2017-06-15
Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.
Pauli, Carla; de Oliveira Thais, Maria Emilia Rodrigues; Guarnieri, Ricardo; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim; Ben, Juliana; Linhares, Marcelo Neves; Markowitsch, Hans Joachim; Wolf, Peter; Wiebe, Samuel; Lin, Katia; Walz, Roger
2017-10-01
The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE. Copyright © 2017 Elsevier Inc. All rights reserved.
Laverick, Rosanna; Haddow, Lewis; Daskalopoulou, Marina; Lampe, Fiona; Gilson, Richard; Speakman, Andrew; Antinori, Andrea; Bruun, Tina; Vassilenko, Anna; Collins, Simon; Rodger, Alison
2017-11-01
We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive adults in 5 European clinics. HIV+ adults underwent computerized and pen-and-paper neuropsychological tests and questionnaires of cognitive symptoms and ADLs. We considered cognitive function in 5 domains, psychosocial factors, and clinical parameters as potentially associated with symptoms. Separate regression analyses were used to determine factors associated with a decline in ADL (defined as self-reported decline affecting ≥2 ADLs and attributed to cognitive difficulties) and self-reported frequency of symptoms of cognitive impairment. We also estimated the diagnostic accuracy of both questionnaires as tests for cognitive impairment. Four hundred forty-eight patients completed the assessments [mean age 45.8 years, 84% male, 87% white, median CD4 count 550 cells/mm, median time since HIV diagnosis 9.9 years, 81% virologically suppressed (HIV-1 plasma RNA <50 copies/mL)]. Ninety-six (21.4%) reported decline in ADLs and attributed this to cognitive difficulties. Self-reported decline in ADLs and increased symptoms of cognitive impairment were both associated with worse performance on some cognitive tests. There were also strong associations with financial difficulties, depressive and anxiety symptoms, unemployment, and longer time since HIV diagnosis. Both questionnaires performed poorly as diagnostic tests for cognitive impairment. Patients' own assessments of everyday function and symptoms were associated with objectively measured cognitive function. However, there were strong associations with other psychosocial issues including mood and anxiety disorders and socioeconomic hardship. This should be considered when assessing HIV-associated cognitive impairment in clinical care or research studies.
Terminal decline and practice effects in older adults without dementia: the MoVIES project.
Dodge, Hiroko H; Wang, Chia-Ning; Chang, Chung-Chou H; Ganguli, Mary
2011-08-23
To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline. A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point. Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects. Terminal cognitive decline in older adults without dementia may reflect presymptomatic disease which does not cross the clinical threshold during life. Alternatively, cognitive decline attributed to normal aging may itself represent underlying neurodegenerative or vascular pathology. Although we cannot conclude definitively from this study, the separation of practice effects from age-associated decline could help identify preclinical dementia.
Jones, Roy W; Lebrec, Jeremie; Kahle-Wrobleski, Kristin; Dell'Agnello, Grazia; Bruno, Giuseppe; Vellas, Bruno; Argimon, Josep M; Dodel, Richard; Haro, Josep Maria; Wimo, Anders; Reed, Catherine
2017-01-01
We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia.
Morris, Rosie; Lord, Sue; Lawson, Rachael A; Coleman, Shirley; Galna, Brook; Duncan, Gordon W; Khoo, Tien K; Yarnall, Alison J; Burn, David J; Rochester, Lynn
2017-11-09
Dementia is significant in Parkinson's disease (PD) with personal and socioeconomic impact. Early identification of risk is of upmost importance to optimize management. Gait precedes and predicts cognitive decline and dementia in older adults. We aimed to evaluate gait characteristics as predictors of cognitive decline in newly diagnosed PD. One hundred and nineteen participants recruited at diagnosis were assessed at baseline, 18 and 36 months. Baseline gait was characterized by variables that mapped to five domains: pace, rhythm, variability, asymmetry, and postural control. Cognitive assessment included attention, fluctuating attention, executive function, visual memory, and visuospatial function. Mixed-effects models tested independent gait predictors of cognitive decline. Gait characteristics of pace, variability, and postural control predicted decline in fluctuating attention and visual memory, whereas baseline neuropsychological assessment performance did not predict decline. This provides novel evidence for gait as a clinical biomarker for PD cognitive decline in early disease. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.
Lead exposure and rate of change in cognitive function in older women
Power, Melinda C; Korrick, Susan; Tchetgen Tchetgen, Eric J; Nie, Linda H; Grodstein, Francine; Hu, Howard; Weuve, Jennifer; Schwartz, Joel; Weisskopf, Marc G
2014-01-01
Background Higher long-term cumulative lead exposure predicts faster cognitive decline in older men, but evidence of an association in women is lacking. Objective To determine if there is an association between lead exposure and cognitive decline in women. Methods This study considers a sample of 584 women from the Nurses’ Health Study who live in or near Boston, Massachusetts. We quantified lead exposure using biomarkers of lead exposure assessed in 1993–2004 and evaluated cognitive decline by repeated performance on a telephone battery of cognitive tests primarily assessing learning, memory, executive function, and attention completed in 1995–2008. All cognitive test scores were z-transformed for use in analyses. We used linear mixed models with random effects to quantify the association between each lead biomarker and change in cognition overall and on each individual test. Results Consideration of individual tests showed greater cognitive decline with increased tibia lead concentrations, a measure of long-term cumulative exposure, for story memory and category fluency. The estimated excess annual decline in overall cognitive test z-score per SD increase in tibia bone lead concentration was suggestive, although the confidence intervals included the null (0.024 standard units, 95% confidence interval: −0.053 , 0.004 – an additional decline in function equivalent to being 0.33 years older). We found little support for associations between cognitive decline and patella or blood lead, which provide integrated measures of exposure over shorter timeframes. Conclusions Long-term cumulative lead exposure may be weakly associated with faster cognitive decline in community-dwelling women, at least in some cognitive domains. PMID:24529005
Ferris, Steven; Nordberg, Agneta; Soininen, Hilkka; Darreh-Shori, Taher; Lane, Roger
2014-01-01
Objective Evaluate the influence of gender and butyrylcholinesterase (BuChE) genotype on incidence of progression to AD, rate of cognitive and functional decline, and response to rivastigmine treatment in mild cognitive impairment (MCI) subjects. Methods This retrospective exploratory analysis from a 3–4 year, randomized, placebo-controlled study of rivastigmine in MCI subjects included participants who consented to pharmacogenetic testing. Results Of 1018 total patients, 490 (253 [52%] female) were successfully genotyped for BuChE. In subjects receiving placebo, the BuChE wt/wt genotype was associated with a statistically significantly higher rate of progression to AD and functional decline in women, compared with men with the BuChE wt/wt genotype. In subjects with a BuChE-K allele receiving placebo, incidence of progression to AD and rate of functional decline were not significantly different by gender, however cognitive decline was significantly faster in men. Statistically significant benefits of rivastigmine treatment on progression to AD, functional decline, ventricular volume expansion, whole brain atrophy and white matter loss were evident in female BuChE wt/wt. Conclusion Gender appears to differentially influence the type of decline in MCI subjects according to BuChE genotype, with more rapid progression of cognitive decline in male BuChE-K, and more rapid progression to AD and functional decline in female BuChE wt/wt. Cognitive decline in male BuChE-K and functional decline and progression to AD in female BuChE wt/wt were significantly attenuated by rivastigmine. Rivastigmine treatment also significantly reduced ventricular expansion, whole brain atrophy rate and white matter loss in female BuChE wt/wt, suggesting a possible disease-modifying effect. PMID:19617863
Central obesity, leptin and cognitive decline: the Sacramento Area Latino Study on Aging.
Zeki Al Hazzouri, Adina; Haan, Mary N; Whitmer, Rachel A; Yaffe, Kristine; Neuhaus, John
2012-01-01
Central obesity is a risk factor for cognitive decline. Leptin is secreted by adipose tissue and has been associated with better cognitive function. Aging Mexican Americans have higher levels of obesity than non-Hispanic Whites, but no investigations examined the relationship between leptin and cognitive decline among them or the role of central obesity in this association. We analyzed 1,480 dementia-free older Mexican Americans who were followed over 10 years. Cognitive function was assessed every 12-15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT). For females with a small waist circumference (≤35 inches), an interquartile range difference in leptin was associated with 35% less 3MSE errors and 22% less decline in the SEVLT score over 10 years. For males with a small waist circumference (≤40 inches), an interquartile range difference in leptin was associated with 44% less 3MSE errors and 30% less decline in the SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with a large waist circumference. Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function. Copyright © 2012 S. Karger AG, Basel.
Widowhood Status as a Risk Factor for Cognitive Decline among Older Adults.
Shin, Su Hyun; Kim, Giyeon; Park, Soohyun
2018-07-01
This study investigated whether widowhood status has an effect on cognitive decline among older adults in the United States. Longitudinal analysis of existing secondary data. The 1996-2012 waves of the Health and Retirement Study. A total of 6,766 individuals (28,420 observations) aged 50 years and older who responded to all questions. Widow/widower status, cognitive functioning score, and various covariates. Growth-curve models show that after controlling for covariates, widowhood status was related to cognitive decline (95% CI: -0.8090, -0.4674). We also found a linear relationship between time since spousal loss and cognitive decline. Conditional upon spousal bereavement status, higher education and having at least one living sibling were found to be protective factors against cognitive decline. Widowhood status accelerated cognitive decline over time among widowed older adults. Findings suggest that extra support is needed to monitor cognitive functioning for those experiencing widowhood. Copyright © 2018 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Yeh, Ting-Ting; Wu, Ching-Yi; Hsieh, Yu-Wei; Chang, Ku-Chou; Lee, Lin-Chien; Hung, Jen-Wen; Lin, Keh-Chung; Teng, Ching-Hung; Liao, Yi-Han
2017-08-31
Aerobic exercise and cognitive training have been effective in improving cognitive functions; however, whether the combination of these two can further enhance cognition and clinical outcomes in stroke survivors with cognitive decline remains unknown. This study aimed to determine the treatment effects of a sequential combination of aerobic exercise and cognitive training on cognitive function and clinical outcomes. Stroke survivors (n = 75) with cognitive decline will be recruited and randomly assigned to cognitive training, aerobic exercise, and sequential combination of aerobic exercise and cognitive training groups. All participants will receive training for 60 minutes per day, 3 days per week for 12 weeks. The aerobic exercise group will receive stationary bicycle training, the cognitive training group will receive cognitive-based training, and the sequential group will first receive 30 minutes of aerobic exercise, followed by 30 minutes of cognitive training. The outcome measures involve cognitive functions, physiological biomarkers, daily function and quality of life, physical functions, and social participation. Participants will be assessed before and immediately after the interventions, and 6 months after the interventions. Repeated measures of analysis of variance will be used to evaluate the changes in outcome measures at the three assessments. This trial aims to explore the benefits of innovative intervention approaches to improve the cognitive function, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline. The findings will provide evidence to advance post-stroke cognitive rehabilitation. ClinicalTrials.gov, NCT02550990 . Registered on 6 September 2015.
Athey, Richard J; Walker, Richard W
2006-10-01
Cognitive impairment is well recognised in Parkinson's Disease (PD) but few studies have examined cognitive decline over time in such subjects. Standard clinical assessments of cognitive function, such as the MMSE, do not measure all cognitive domains and often have a ceiling effect. CAMCOG-R provides a more comprehensive cognitive assessment allowing several different domains of cognition to be compared. It also features the ability to test 'executive function'. CAMCOG-R has only been reported on one previous occasion in PD subjects and this is the first study to report a follow-up CAMCOG-R to assess cognitive decline. In a previously published study CAMCOG-R was administered to a prevalent community-based population of 94 subjects with PD with a MMSE of 25 or above. In this subsequent study 85 of the subjects (two declined and seven were deceased) underwent a follow-up CAMCOG-R after a mean delay of 13.1 months. The initial, and follow-up mean total CAMCOG-R scores were 88.65/104 and 84.75/104 respectively, demonstrating a significant decline (p < 0.05). Significant cognitive decline (p < 0.05) was also seen across every CAMCOG-R cognitive domain and in the executive function scores. A wide range of cognitive ability was again demonstrated using CAMCOG-R in this PD population. The decline of 3.9 CAMCOG-R points over the 13-month period compares to other previous studies showing an annual decline of 1.6 CAMCOG points in normal elderly individuals and 12 CAMCOG points annually in those with established dementia. This study suggests that CAMCOG-R is a useful and appropriate tool for use in follow-up cognitive screening in PD subjects. Copyright (c) 2006 John Wiley & Sons, Ltd.
Hajjar, Ihab; Goldstein, Felicia C; Martin, Greg S; Quyyumi, Arshed A
2016-01-01
Although there is strong evidence that hypertension leads to cognitive decline, especially in the executive domain, the relationship between blood pressure and cognition has been conflicted. Hypertension is characterized by blood pressure elevation and increased arterial stiffness. We aimed at investigating whether arterial stiffness would be superior to blood pressure in predicting cognitive decline and explaining the hypertension-executive decline association. A randomly selected asymptomatic population (n=591, age=49.2 years, 70% women, 27% black, and education=18 years) underwent annual vascular and cognitive assessments. Cognition was assessed using computerized versions commonly used cognitive tests, and principal component analysis was used for deriving cognitive scores for executive function, memory, and working memory. Arterial stiffness was measured by carotid-femoral pulse wave velocity (PWV). Higher PWV, but not blood pressure, was associated with a steeper decline in executive (P=0.0002), memory (P=0.05), and working memory (P=0.02) scores after adjusting for demographics, education, and baseline cognitive performance. This remained true after adjusting for hypertension. Hypertension was associated with greater decline in executive score (P=0.0029) and those with combined hypertension and elevated PWV (>7 m/s) had the greatest decline in executive score (P value hypertension×PWV=0.02). PWV explained the association between hypertension and executive function (P value for hypertension=0.0029 versus 0.24 when adjusting for PWV). In healthy adults, increased arterial stiffness is superior to blood pressure in predicting cognitive decline in all domains and in explaining the hypertension-executive function association. Arterial stiffness, especially in hypertension, may be a target in the prevention of cognitive decline. © 2015 American Heart Association, Inc.
Effect of retirement on cognitive function: the Whitehall II cohort study.
Xue, Baowen; Cadar, Dorina; Fleischmann, Maria; Stansfeld, Stephen; Carr, Ewan; Kivimäki, Mika; McMunn, Anne; Head, Jenny
2017-12-26
According to the 'use it or lose it' hypothesis, a lack of mentally challenging activities might exacerbate the loss of cognitive function. On this basis, retirement has been suggested to increase the risk of cognitive decline, but evidence from studies with long follow-up is lacking. We tested this hypothesis in a cohort of 3433 civil servants who participated in the Whitehall II Study, including repeated measurements of cognitive functioning up to 14 years before and 14 years after retirement. Piecewise models, centred at the year of retirement, were used to compare trajectories of verbal memory, abstract reasoning, phonemic verbal fluency, and semantic verbal fluency before and after retirement. We found that all domains of cognition declined over time. Declines in verbal memory were 38% faster after retirement compared to before, after taking account of age-related decline. In analyses stratified by employment grade, higher employment grade was protective against verbal memory decline while people were still working, but this 'protective effect' was lost when individuals retired, resulting in a similar rate of decline post-retirement across employment grades. We did not find a significant impact of retirement on the other cognitive domains. In conclusion, these findings are consistent with the hypothesis that retirement accelerates the decline in verbal memory function. This study points to the benefits of cognitively stimulating activities associated with employment that could benefit older people's memory.
Krüger, Melanie; Hinder, Mark R; Puri, Rohan; Summers, Jeffery J
2017-01-01
Objectives: The aim of this study was to investigate how age-related performance differences in a visuospatial sequence learning task relate to age-related declines in cognitive functioning. Method: Cognitive functioning of 18 younger and 18 older participants was assessed using a standardized test battery. Participants then undertook a perceptual visuospatial sequence learning task. Various relationships between sequence learning and participants' cognitive functioning were examined through correlation and factor analysis. Results: Older participants exhibited significantly lower performance than their younger counterparts in the sequence learning task as well as in multiple cognitive functions. Factor analysis revealed two independent subsets of cognitive functions associated with performance in the sequence learning task, related to either the processing and storage of sequence information (first subset) or problem solving (second subset). Age-related declines were only found for the first subset of cognitive functions, which also explained a significant degree of the performance differences in the sequence learning task between age-groups. Discussion: The results suggest that age-related performance differences in perceptual visuospatial sequence learning can be explained by declines in the ability to process and store sequence information in older adults, while a set of cognitive functions related to problem solving mediates performance differences independent of age.
Occupational cognitive requirements and late-life cognitive aging.
Pool, Lindsay R; Weuve, Jennifer; Wilson, Robert S; Bültmann, Ute; Evans, Denis A; Mendes de Leon, Carlos F
2016-04-12
To examine whether occupational cognitive requirements, as a marker of adulthood cognitive activity, are associated with late-life cognition and cognitive decline. Main lifetime occupation information for 7,637 participants aged >65 years of the Chicago Health and Aging Project (CHAP) was linked with standardized data on worker attributes and job characteristics from the Occupational Information Network (O*NET). Ratings of cognitive processes required in 10 work-related tasks were used to create a summary measure of occupational cognitive requirements (possible range 0-7). Multivariable-adjusted linear mixed models were used to estimate the association of occupational cognitive requirements score (OCRS) with cognitive function and rate of cognitive decline. Higher OCRS corresponded to significantly better late-life cognitive performance at baseline in 1993 (p < 0.001) and to slower decline in global cognitive function over time (p = 0.004). Within a genotyped subsample (n = 4,104), the associations of OCRS with rate of cognitive decline did not differ significantly by APOE ε4 carriership (p = 0.11). Findings suggest that occupational cognitive requirements are associated with better cognition and a slower rate of cognitive decline in older age. Adulthood cognitive activity may contribute to cognitive reserve in late life. © 2016 American Academy of Neurology.
Cognitive Decline and Its Risk Factors in Prevalent Hemodialysis Patients.
Drew, David A; Weiner, Daniel E; Tighiouart, Hocine; Duncan, Sarah; Gupta, Aditi; Scott, Tammy; Sarnak, Mark J
2017-06-01
Cognitive impairment is common in patients treated with hemodialysis. The trajectory of cognitive function and risk factors for cognitive decline remain uncertain in this population. Longitudinal cohort. 314 prevalent hemodialysis patients. Age, sex, race, education level, hemodialysis vintage, cause of end-stage renal disease, and baseline history of cardiovascular disease. Cognitive function as determined by a comprehensive neurocognitive battery, administered at baseline and yearly when possible. Individual cognitive test results were reduced into 2 domain scores using principal components analysis, representing memory and executive function, which were used as our coprimary outcomes and by definition have a mean of zero and SD of 1. Mean age was 63 years; 54% were men, 22% were black, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 0.9-4.2) years, 196 had at least 1 follow-up test, 156 died, and 43 received a kidney transplant. Linear mixed models and joint models, which accounted for competing risks from death, dropout, or kidney transplantation, showed nearly identical results. The joint model demonstrated a decline in executive function (-0.09 [95% CI, -0.13 to -0.05] SD per year), whereas memory improved slightly (0.05 [95% CI, 0.02 to 0.08] SD per year). A significant yearly decline was also seen in the Mini-Mental State Examination score (median change, -0.41; 95% CI, -0.57 to -0.25). Older age was the only significant risk factor for steeper executive function decline (-0.04 [95% CI, -0.06 to -0.02] SD steeper annual decline for each 10 years of age). Prevalent hemodialysis patients only, limited follow-up testing due to high mortality rate, and exclusion of participants with severe cognitive deficits or dementia. Prevalent hemodialysis patients demonstrate significant cognitive decline, particularly within tests of executive function. Older age was the only statistically significant risk factor for steeper cognitive decline, which may have important clinical consequences for patient management and education. Future studies should evaluate strategies to maintain or improve cognitive function. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Yamada, Michiko; Landes, Reid D; Mimori, Yasuyo; Nagano, Yoshito; Sasaki, Hideo
2015-04-15
To investigate associations between age, sex, education, and birth cohort and global cognitive decline among a population that would most likely not progress to dementia. A total of 1538 dementia-free subjects aged 60 to 80years in 1992 were followed up through 2011 without dementia occurrence. We assessed cognitive function using the Cognitive Ability Screening Instrument (CASI). Using stepwise-like model selection procedure, we built mixed-effects models for initial cognition and longitudinal cognition. Initial CASI scores for younger age and more years of formal education were higher than those for older and less education. Sex did not show a significant effect. In the longitudinal analysis, cognitive decline became more rapid with increasing age. Sex and education did not modify the degree of deterioration with age. CASI scores were higher for younger cohorts and men due to differences in education levels. Among dementia-free subjects, age is an important predictor of cognitive function level and cognitive decline. Education level affects cognitive function level, but did not affect cognitive decline. The results have implications not only for elucidation of the aging process, but also for reference in dementia screening. Copyright © 2015 Elsevier B.V. All rights reserved.
Kidney function and cognitive decline in an oldest-old Chinese population.
Bai, Kunhao; Pan, Yujing; Lu, Fanghong; Zhao, Yingxin; Wang, Jinwei; Zhang, Luxia
2017-01-01
Early-stage chronic kidney disease has been suggested to be correlated with cognitive decline, but the association has rarely been explored in the oldest old. This prospective study included 284 Chinese participants aged 80 years or older with serum creatinine levels <150 µmol/L. The median follow-up time was 3.3 years, and 247 (87.0%) participants provided valid data at their last visit. Kidney function was evaluated by measuring the estimated glomerular filtration rate (eGFR) at baseline, and cognitive function was evaluated using the Mini-Mental State Examination (MMSE) at both baseline and annual visits. A reliable decrease in the MMSE score over the follow-up period was observed based on a Reliable Change Index of 1.645 (equivalent to a 90% confidence interval [CI]), which was used to define cognitive decline. Poisson regression models were built to analyze the association between baseline kidney function and cognitive decline. A total of 18 (7.3%) cases of incident cognitive decline were observed during the follow-up period. After adjusting for potential confounders, the relative risk of developing cognitive decline was 4.03 (95% CI 1.09-13.81) among participants with an eGFR of 30-59 mL/min/1.73 m 2 compared to participants with an eGFR of ≥60 mL/min/1.73 m 2 . Early-stage chronic kidney disease was correlated with cognitive decline in an oldest-old Chinese population.
Preservation of cognitive and functional ability as markers of longevity.
Schupf, Nicole; Costa, Rosann; Tang, Ming-Xin; Andrews, Howard; Tycko, Benjamin; Lee, Joseph H; Mayeux, Richard
2004-10-01
Longevity is a complex biological process for which the phenotypes have not been established. Preservation of cognitive and physical function may be important and preservation of these functions is, in part, inherited. We investigated the relation between rate of change in cognitive and functional abilities in probands and risk of death in their siblings. Probands were classified as showing no decline, slow, medium, or rapid rate of decline, based on the slope of change in cognitive and physical/functional factors over three or more assessments. Siblings of probands who did not decline on measures of memory, visuospatial/cognitive function or ADL skills were approximately half as likely to die as siblings of probands who had the most rapid decline. The reduction in risk of death in siblings of probands who did not decline in was primarily observed among siblings of probands who were older than 75 years, suggesting that genetic influences on life span may be greater at older ages. There was no association between probands' rate of change in language, IADL skills, upper or lower extremity mobility and risk of death in siblings. The results of the present study identify phenotypes associated with preserved cognitive and functional abilities which may serve as markers for longevity.
Jones, Roy W.; Lebrec, Jeremie; Kahle-Wrobleski, Kristin; Dell'Agnello, Grazia; Bruno, Giuseppe; Vellas, Bruno; Argimon, Josep M.; Dodel, Richard; Haro, Josep Maria; Wimo, Anders; Reed, Catherine
2017-01-01
Background/Aims We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. Methods Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. Results Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. Conclusion Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia. PMID:28611822
Jiskoot, Lize C; Panman, Jessica L; van Asseldonk, Lauren; Franzen, Sanne; Meeter, Lieke H H; Donker Kaat, Laura; van der Ende, Emma L; Dopper, Elise G P; Timman, Reinier; van Minkelen, Rick; van Swieten, John C; van den Berg, Esther; Papma, Janne M
2018-06-01
We performed 4-year follow-up neuropsychological assessment to investigate cognitive decline and the prognostic abilities from presymptomatic to symptomatic familial frontotemporal dementia (FTD). Presymptomatic MAPT (n = 15) and GRN mutation carriers (n = 31), and healthy controls (n = 39) underwent neuropsychological assessment every 2 years. Eight mutation carriers (5 MAPT, 3 GRN) became symptomatic. We investigated cognitive decline with multilevel regression modeling; the prognostic performance was assessed with ROC analyses and stepwise logistic regression. MAPT converters declined on language, attention, executive function, social cognition, and memory, and GRN converters declined on attention and executive function (p < 0.05). Cognitive decline in ScreeLing phonology (p = 0.046) and letter fluency (p = 0.046) were predictive for conversion to non-fluent variant PPA, and decline on categorical fluency (p = 0.025) for an underlying MAPT mutation. Using longitudinal neuropsychological assessment, we detected a mutation-specific pattern of cognitive decline, potentially suggesting prognostic value of neuropsychological trajectories in conversion to symptomatic FTD.
Olfactory discrimination predicts cognitive decline among community-dwelling older adults
Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N
2012-01-01
The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46–86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio=0.869; P<0.05; 95% confidence interval=0.764−0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia. PMID:22832962
Olfactory discrimination predicts cognitive decline among community-dwelling older adults.
Sohrabi, H R; Bates, K A; Weinborn, M G; Johnston, A N B; Bahramian, A; Taddei, K; Laws, S M; Rodrigues, M; Morici, M; Howard, M; Martins, G; Mackay-Sim, A; Gandy, S E; Martins, R N
2012-05-22
The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions using the Sniffin' Sticks battery indicated that, contrary to previous findings, olfactory discrimination, but not olfactory identification, significantly predicted subsequent cognitive decline (odds ratio = 0.869; P<0.05; 95% confidence interval = 0.764-0.988). The current study findings confirm previously reported associations between olfactory and cognitive functions, and indicate that impairment in olfactory discrimination can predict future cognitive decline. These findings further our current understanding of the association between cognition and olfaction, and support olfactory assessment in screening those at higher risk of dementia.
Neurogranin as a predictor of memory and executive function decline in MCI patients.
Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan
2018-03-06
To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.
Todoriki, Hidemi; Higashiuesato, Yasushi; Yasura, Shotoku; Willcox, D. Craig; Ohya, Yusuke; Willcox, Bradley J.; Dodge, Hiroko H.
2012-01-01
The study aim was to test whether the metabolic syndrome or its components predicted cognitive decline among persons aged 80 years and older (mean 85.0 years). Participants were members of the “Keys to Optimal Cognitive Aging Project,” a prospective cohort study in Okinawa, Japan. Metabolic syndrome was assessed at baseline. Cognitive functions were assessed annually for up to 3 years. One hundred and forty-eight participants completed at least one follow-up with 101 participating in all three assessments and 47 participating in two of the three assessments. The mean and median duration of follow-up were 1.8 and 2 years, respectively. Metabolic syndrome and four components were not associated with decline in global and executive cognitive functions. However, high glycosylated hemoglobin was associated with decline in memory function at the second follow-up. Our study supports accumulating evidence that the positive association between metabolic syndrome and cognitive function might not hold for the oldest old. PMID:22016359
Does a patent foramen ovale influence cognitive function in dialysis patients?
George, Sudhakar; Holt, Stephen; Medford, Nick; Hildick-Smith, David
2013-01-01
Patients with chronic kidney disease on dialysis treatment have poorer cognitive function than age- and sex-matched controls. One proposed mechanism is cerebral microembolisation due to material from the dialysis circuit crossing a patent foramen ovale (PFO). Cognitive testing was carried out in haemodialysis (HD) patients and peritoneal dialysis (PD) patients. Transthoracic echocardiography was used to identify PFO. Follow-up testing 1 year later enabled comparison of cognitive decline between patients with and without a PFO, and between those undergoing different dialysis modalities. 80 patients (aged 60.4 ± 15.0 years) were recruited (51 HD patients and 29 PD controls). A PFO was found in 21% of patients. 83% of dialysis patients suffered a decline in one or more cognitive function tests over 1 year. There was a significant difference in only one test between HD patients with or without a PFO. PD patients showed a more rapid cognitive decline than those on HD. Cognitive decline in dialysis patients is rapid and affects most patients. The presence of a PFO made only subtle differences to the rates of cognitive decline during 1 year of follow-up. Patients with a PFO should not be prevented from considering HD because of concerns of cerebral decline due to microembolisation. Copyright © 2013 S. Karger AG, Basel.
Guerrero-Berroa, Elizabeth; Luo, Xiaodong; Schmeidler, James; Rapp, Michael A; Dahlman, Karen; Grossman, Hillel T; Haroutunian, Vahram; Beeri, Michal Schnaider
2009-12-01
The mini-mental state exam (MMSE) has been used to address questions such as determination of appropriate cutoff scores for differentiation of individuals with intact cognitive function from patients with dementia and rate of cognitive decline. However, little is known about the relationship of performance in specific cognitive domains to subsequent overall decline. To examine the specific and/or combined contribution of four MMSE domains (orientation for time, orientation for place, delayed recall, and attention) to prediction of overall cognitive decline on the MMSE. Linear mixed models were applied to 505 elderly nursing home residents (mean age = 85, > 12 years education = 27%; 79% F, mean follow-up = 3.20 years) to examine the relationship between baseline scores of these domains and total MMSE scores over time. Orientation for time was the only domain significantly associated with MMSE decline over time. Combination of poor delayed recall with either attention or orientation for place was associated with significantly increased decline on the MMSE. The MMSE orientation for time predicts overall decline on MMSE scores over time. A good functioning domain added to good functioning delayed recall was associated with slower rate of decline. Copyright (c) 2009 John Wiley & Sons, Ltd.
Shirooka, Hidehiko; Nishiguchi, Shu; Fukutani, Naoto; Tashiro, Yuto; Nozaki, Yuma; Aoyama, Tomoki
2018-05-01
The association between subjective cognitive decline and falls has not been clearly determined. Our aim was to explore the effect of subjective cognitive decline on falls in community-dwelling older adults with or without objective cognitive decline. We included 470 older adults (mean age 73.6 ± 5.2; 329 women) living in the community and obtained data on fall history directly from the participants. Subjective cognitive decline was assessed using a self-administered question. Objective cognitive function was measured using the Mini-Mental State Examination. Statistical analyses were carried out separately for participants with objective cognitive decline and those without. A multiple logistic regression analysis showed that, among participants without objective cognitive decline, subjective cognitive decline was positively associated with falls [OR 1.91; 95% confidence interval (CI) 1.17-3.12; p = 0.01). Conversely, among participants with objective cognitive decline, subjective cognitive decline was negatively associated with falls (OR 0.07; 95% CI 0.01-0.85, p = 0.04). The result suggests that the objective-subjective disparity may affect falls in community-dwelling older adults. The presence of subjective cognitive decline was significantly positively associated with falls among cognitively intact older adults. However, among their cognitively impaired peers, the absence of subjective cognitive decline was positively associated with falls.
Wilson, Craig J; Cohen, Harvey Jay; Pieper, Carl F
2003-10-01
To investigate the effect of coagulation and inflammatory pathway activation on future cognitive decline in older persons. Prospective cohort study. Rural and urban communities in North Carolina. Community-dwelling older people enrolled in the Duke Established Populations for Epidemiologic Studies of the Elderly in 1986. In 1992, blood was drawn for assay of D-dimer (1,723 subjects), Interleukin-6 (1,726 subjects), and other cytokines (1,551 subjects). Cognitive and functional assessments were performed in 1986, 1989, 1992, and 1996. Cognition was measured using the Short Portable Mental Status Questionnaire. Cognitive decline over a 4-year period was significantly correlated (P<.001) with D-dimer, age, race, and physical performance status as measured using the Rosow-Breslau and Nagi instruments. After controlling for demographics, functional status, and comorbidities, D-dimer remained predictive of cognitive decline. Proinflammatory cytokines were not associated with current cognitive status in cross-sectional analyses or with incident cognitive decline in prospective analyses. In a large sample of community-dwelling elders, higher levels of D-dimer were predictive of cognitive decline over a 4-year period. No clinically significant associations were found between age-related peripheral cytokine dysregulation and cognition.
Biomarkers for cognitive decline in patients with diabetes mellitus: evidence from clinical studies
Zhao, Xue; Han, Qing; Lv, You; Sun, Lin; Gang, Xiaokun; Wang, Guixia
2018-01-01
Diabetes mellitus is considered as an important factor for cognitive decline and dementia in recent years. However, cognitive impairment in diabetic patients is often underestimated and kept undiagnosed, leading to thousands of diabetic patients suffering from worsening memory. Available reviews in this field were limited and not comprehensive enough. Thus, the present review aimed to summarize all available clinical studies on diabetic patients with cognitive decline, and to find valuable biomarkers that might be applied as diagnostic and therapeutic targets of cognitive impairment in diabetes. The biomarkers or risk factors of cognitive decline in diabetic patients could be classified into the following three aspects: serum molecules or relevant complications, functional or metabolic changes by neuroimaging tools, and genetic variants. Specifically, factors related to poor glucose metabolism, insulin resistance, inflammation, comorbid depression, micro-/macrovascular complications, adipokines, neurotrophic molecules and Tau protein presented significant changes in diabetic patients with cognitive decline. Besides, neuroimaging platform could provide more clues on the structural, functional and metabolic changes during the cognitive decline progression of diabetic patients. Genetic factors related to cognitive decline showed inconsistency based on the limited studies. Future studies might apply above biomarkers as diagnostic and treatment targets in a large population, and regulation of these parameters might shed light on a more valuable, sensitive and specific strategy for the diagnosis and treatment of cognitive decline in diabetic patients. PMID:29484146
Validation analysis of informant's ratings of cognitive function in African Americans and Nigerians
Shen, Jianzhao; Gao, Sujuan; Unverzagt, Frederick W.; Ogunniyi, Adesola; Baiyewu, Olusegun; Gureje, Oye; Hendrie, Hugh C.; Hall, Kathleen S.
2011-01-01
SUMMARY Objectives To examine informant validity using the Community Screening Interview for Dementia (CSI ‘D’) both cross-sectionally and longitudinally in two very different cultures and to explore the effects of informants and study participants’ characteristics on the validity of informants’ reports. Methods Elderly African Americans age 65 years and older residing in Indianapolis, USA and elderly Yoruba Nigerians age 65 years and older residing in Ibadan, Nigeria were assessed on cognitive functioning using the CSI ‘D’ at baseline (1992–1993) and five-year follow-up (1997–1998). At baseline, the informant validity in both samples was evaluated against participants’ cognitive tests using Pearson correlation and regular regression models. At follow-up, informants ratings on cognitive decline were assessed against participants’ cognitive decline scores from baseline to follow-up using biserial correlation and logistic regressions. Results At baseline, informants’ reports on cognitive functioning significantly correlated with cognitive scores in both samples (Indianapolis:r = –0.43, p < 0.001; Ibadan:r = –0.47, p < 0.001). The participant–informant relationships significantly affected the informants’ reports in the two samples with different patterns (p = 0.005 for Indianapolis and p < 0.001 for Ibadan) at a given level of cognitive functioning. African Americans spouses reported more cognitive problems, while siblings reported more problems for the Yoruba Nigerians. At follow-up, informants’ ratings on cognitive decline significantly correlated with the cognitive decline scores (Indianapolis r = 0.38, p < 0.001; Ibadan r = 0.32, p < 0.001). The characteristics of study participants and informants had little impact on the informants’ ratings on cognitive decline. Conclusions Informant reports are valid in assessing the cognitive functioning of study participants both cross-sectionally and longitudinally in two very different cultures, languages and environments. PMID:16802282
Dietary Sodium/Potassium Intake Does Not Affect Cognitive Function or Brain Imaging Indices.
Nowak, Kristen L; Fried, Linda; Jovanovich, Anna; Ix, Joachim; Yaffe, Kristine; You, Zhiying; Chonchol, Michel
2018-01-01
Dietary sodium may influence cognitive function through its effects on cerebrovascular function and cerebral blood flow. The aim of this study was to evaluate the association of dietary sodium intake with cognitive decline in community-dwelling older adults. We also evaluated the associations of dietary potassium and sodium:potassium intake with cognitive decline, and associations of these nutrients with micro- and macro-structural brain magnetic resonance imaging (MRI) indices. In all, 1,194 participants in the Health Aging and Body Composition study with measurements of dietary sodium intake (food frequency questionnaire [FFQ]) and change in the modified Mini Mental State Exam (3MS) were included. The age of participants was 74 ± 3 years with a mean dietary sodium intake of 2,677 ± 1,060 mg/day. During follow-up (6.9 ± 0.1 years), 340 (28%) had a clinically significant decline in 3MS score (≥1.5 SD of mean decline). After adjustment, dietary sodium intake was not associated with odds of cognitive decline (OR 0.96, 95% CI 0.50-1.84 per doubling of sodium). Similarly, potassium was not associated with cognitive decline; however, higher sodium:potassium intake was associated with increased odds of cognitive decline (OR 2.02 [95% CI 1.01-4.03] per unit increase). Neither sodium or potassium alone nor sodium:potassium were associated with micro- or macro-structural brain MRI indices. These results are limited by the use of FFQ. In community-dwelling older adults, higher sodium:potassium, but not sodium or potassium intake alone, was associated with decline in cognitive function, with no associations observed with micro- and macro-structural brain MRI indices. These findings do not support reduction dietary sodium/increased potassium intake to prevent cognitive decline with aging. © 2018 S. Karger AG, Basel.
Madden, David J.; Parks, Emily L.; Tallman, Catherine W.; Boylan, Maria A.; Hoagey, David A.; Cocjin, Sally B.; Packard, Lauren E.; Johnson, Micah A.; Chou, Ying-hui; Potter, Guy G.; Chen, Nan-kuei; Siciliano, Rachel E.; Monge, Zachary A.; Honig, Jesse A.; Diaz, Michele T.
2017-01-01
Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white matter integrity, resting-state functional connectivity, and white matter hyperintensity (WMH) volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the three imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function. PMID:28389085
Personality and Cognitive Decline in Older Adults: Data From a Longitudinal Sample and Meta-Analysis
Terracciano, Antonio; Stephan, Yannick; Sutin, Angelina R.
2016-01-01
Objectives: Personality traits are associated with risk of dementia; less is known about their association with the trajectory of cognitive functioning. This research examines the association between the 5 major dimensions of personality and cognitive function and decline in older adulthood and includes a meta-analysis of published studies. Method: Personality traits, objective and subjective memory, and cognitive status were collected in a large national sample (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis pooled results from up to 5 prospective studies to examine personality and change in global cognition. Results: Higher Neuroticism was associated with worse performance on all cognitive measures and greater decline in memory, whereas higher Conscientiousness and Openness were associated with better memory performance concurrently and less decline over time. All traits were associated with subjective memory. Higher Conscientiousness and lower Extraversion were associated with better cognitive status and less decline. Although modest, these associations were generally larger than that of hypertension, diabetes, history of psychological treatment, obesity, smoking, and physical inactivity. The meta-analysis supported the association between Neuroticism and Conscientiousness and cognitive decline. Discussion: Personality is associated with cognitive decline in older adults, with effects comparable to established clinical and lifestyle risk factors. PMID:25583598
Dodge, Hiroko H; Zhu, Jian; Harvey, Danielle; Saito, Naomi; Silbert, Lisa C; Kaye, Jeffrey A; Koeppe, Robert A; Albin, Roger L
2014-11-01
It is unknown which commonly used Alzheimer disease (AD) biomarker values-baseline or progression-best predict longitudinal cognitive decline. 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Cognitive Decline in Older Persons Initiating Anticholinergic Medications
Shah, Raj C.; Janos, Alicia L.; Kline, Julia E.; Yu, Lei; Leurgans, Sue E.; Wilson, Robert S.; Wei, Peter; Bennett, David A.; Heilman, Kenneth M.; Tsao, Jack W.
2013-01-01
Background This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. Methods Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. Results Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was −0.062 (SE = 0.005), −0.081(SE = 0.011), and −0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = −0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). Conclusions Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications. PMID:23741303
[Functional impairment associated with cognitive impairment in hospitalised elderly].
Ocampo-Chaparro, José Mauricio; Mosquera-Jiménez, José Ignacio; Davis, Annabelle S; Reyes-Ortiz, Carlos A
The aim of this study was to analyse the effect of cognitive impairment on functional decline in hospitalised patients aged ≥60 years. Measurements at admission included demographic data, Charlson's comorbidity index, and cognitive impairment (according to education level). Data were also collected on hospital length of stay, depression, and delirium developed during hospitalisation. The outcome, Barthel Index (BI), was measured at admission, discharge, and 1-month post-discharge. Patients with BI≤75 at admission (n=54) or with a missing BI value were excluded (n=1). Multivariate logistic regression analyses were conducted to explore predictive factors with functional decline (BI≤75) from admission to discharge, and 1-month later. Of the 133 patients included, 24.8% and 19.6% had a BI≤75 at discharge and at 1-month, respectively. Compared with men, women had more than double risk for functional decline at discharge and 1-month (P<.05). Compared with those without delirium and without cognitive impairment, those with delirium and cognitive impairment had an increased risk for functional decline (BI≤75) at discharge (OR 5.15, 95% CI; 1.94-13.67), and at 1-month (OR 6.26, 95% CI; 2.30-17.03). Similarly, those with comorbidity (≥2) had increased functional decline at discharge (OR 2.36, 95% CI; 1.14-4.87), and at 1-month after discharge (OR 2.71, 95% CI; 1.25-5.89). Delirium during hospitalisation, together with cognitive impairment on admission, was a strong predictor of functional decline. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.
Left Ventricular Hypertrophy and Cognitive Decline in Old Age.
Mahinrad, Simin; Vriend, Annelotte E; Jukema, J Wouter; van Heemst, Diana; Sattar, Naveed; Blauw, Gerard Jan; Macfarlane, Peter W; Clark, Elaine N; de Craen, Anton J M; Sabayan, Behnam
2017-01-01
Patients with advanced heart failure run a greater risk of dementia. Whether early cardiac structural changes also associate with cognitive decline is yet to be determined. We tested whether left ventricular hypertrophy (LVH) derived from electrocardiogram associates with cognitive decline in older subjects at risk of cardiovascular disease. We included 4,233 participants (mean age 75.2 years, 47.8% male) from PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). LVH was assessed from baseline electrocardiograms by measuring the Sokolow-Lyon index. Higher levels of Sokolow-Lyon index indicate higher degrees of LVH. Cognitive domains involving selective attention, processing speed, and immediate and delayed memory were measured at baseline and repeated during a mean follow-up of 3.2 years. At baseline, LVH was not associated with worse cognitive function. During follow-up, participants with higher levels of LVH had a steeper decline in cognitive function including in selective attention (p = 0.009), processing speed (p = 0.010), immediate memory (p < 0.001), and delayed memory (p = 0.002). These associations were independent of cardiovascular risk factors, co-morbidities, and medications. LVH assessed by electrocardiogram associates with steeper decline in cognitive function of older subjects independent of cardiovascular risk factors and co-morbidities. This study provides further evidence on the link between subclinical cardiac structural changes and cognitive decline in older subjects.
Linking late cognitive outcome with glioma surgery location using resection cavity maps.
Hendriks, Eef J; Habets, Esther J J; Taphoorn, Martin J B; Douw, Linda; Zwinderman, Aeilko H; Vandertop, W Peter; Barkhof, Frederik; Klein, Martin; De Witt Hamer, Philip C
2018-05-01
Patients with a diffuse glioma may experience cognitive decline or improvement upon resective surgery. To examine the impact of glioma location, cognitive alteration after glioma surgery was quantified and related to voxel-based resection probability maps. A total of 59 consecutive patients (range 18-67 years of age) who had resective surgery between 2006 and 2011 for a supratentorial nonenhancing diffuse glioma (grade I-III, WHO 2007) were included in this observational cohort study. Standardized neuropsychological examination and MRI were obtained before and after surgery. Intraoperative stimulation mapping guided resections towards neurological functions (language, sensorimotor function, and visual fields). Maps of resected regions were constructed in standard space. These resection cavity maps were compared between patients with and without new cognitive deficits (z-score difference >1.5 SD between baseline and one year after resection), using a voxel-wise randomization test and calculation of false discovery rates. Brain regions significantly associated with cognitive decline were classified in standard cortical and subcortical anatomy. Cognitive improvement in any domain occurred in 10 (17%) patients, cognitive decline in any domain in 25 (42%), and decline in more than one domain in 10 (17%). The most frequently affected subdomains were attention in 10 (17%) patients and information processing speed in 9 (15%). Resection regions associated with decline in more than one domain were predominantly located in the right hemisphere. For attention decline, no specific region could be identified. For decline in information speed, several regions were found, including the frontal pole and the corpus callosum. Cognitive decline after resective surgery of diffuse glioma is prevalent, in particular, in patients with a tumor located in the right hemisphere without cognitive function mapping. © The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
The emerging role of dietary fructose in obesity and cognitive decline
2013-01-01
The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer’s disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet. PMID:23924506
The emerging role of dietary fructose in obesity and cognitive decline.
Lakhan, Shaheen E; Kirchgessner, Annette
2013-08-08
The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer's disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet.
Distinct Aging Effects on Functional Networks in Good and Poor Cognitive Performers
Lee, Annie; Tan, Mingzhen; Qiu, Anqi
2016-01-01
Brain network hubs are susceptible to normal aging processes and disruptions of their functional connectivity are detrimental to decline in cognitive functions in older adults. However, it remains unclear how the functional connectivity of network hubs cope with cognitive heterogeneity in an aging population. This study utilized cognitive and resting-state functional magnetic resonance imaging data, cluster analysis, and graph network analysis to examine age-related alterations in the network hubs’ functional connectivity of good and poor cognitive performers. Our results revealed that poor cognitive performers showed age-dependent disruptions in the functional connectivity of the right insula and posterior cingulate cortex (PCC), while good cognitive performers showed age-related disruptions in the functional connectivity of the left insula and PCC. Additionally, the left PCC had age-related declines in the functional connectivity with the left medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). Most interestingly, good cognitive performers showed age-related declines in the functional connectivity of the left insula and PCC with their right homotopic structures. These results may provide insights of neuronal correlates for understanding individual differences in aging. In particular, our study suggests prominent protection roles of the left insula and PCC and bilateral ACC in good performers. PMID:27667972
Carotid disease at age 73 and cognitive change from age 70 to 76 years: A longitudinal cohort study
Allerhand, Michael; Eadie, Elizabeth; Thomas, Avril; Corley, Janey; Pattie, Alison; Taylor, Adele; Shenkin, Susan D; Cox, Simon; Gow, Alan; Starr, John M; Deary, Ian J
2016-01-01
Cognitive decline and carotid artery atheroma are common at older ages. In community-dwelling subjects, we assessed cognition at ages 70, 73 and 76 and carotid Doppler ultrasound at age 73, to determine whether carotid stenosis was related to cognitive decline. We used latent growth curve models to examine associations between four carotid measures (internal carotid artery stenosis, velocity, pulsatility and resistivity indices) and four cognitive ability domains (memory, visuospatial function, crystallised intelligence, processing speed) adjusted for cognitive ability at age 11, current age, gender and vascular risk factors. Amongst 866 participants, carotid stenosis (median 12.96%) was not associated with cognitive abilities at age 70 or cognitive decline from age 70 to 76. Increased ICA pulsatility and resistivity indices were associated with slower processing speed (both P < 0.001) and worse visuospatial function (P = 0.036, 0.031, respectively) at age 70, and declining crystallised intelligence from ages 70 to 76 (P = 0.008, 0.006, respectively). The findings suggest that vascular stiffening, rather than carotid luminal narrowing, adversely influences cognitive ageing and provides a potential target for ameliorating age-related cognitive decline. PMID:28155579
Carotid disease at age 73 and cognitive change from age 70 to 76 years: A longitudinal cohort study.
Wardlaw, Joanna M; Allerhand, Michael; Eadie, Elizabeth; Thomas, Avril; Corley, Janey; Pattie, Alison; Taylor, Adele; Shenkin, Susan D; Cox, Simon; Gow, Alan; Starr, John M; Deary, Ian J
2017-08-01
Cognitive decline and carotid artery atheroma are common at older ages. In community-dwelling subjects, we assessed cognition at ages 70, 73 and 76 and carotid Doppler ultrasound at age 73, to determine whether carotid stenosis was related to cognitive decline. We used latent growth curve models to examine associations between four carotid measures (internal carotid artery stenosis, velocity, pulsatility and resistivity indices) and four cognitive ability domains (memory, visuospatial function, crystallised intelligence, processing speed) adjusted for cognitive ability at age 11, current age, gender and vascular risk factors. Amongst 866 participants, carotid stenosis (median 12.96%) was not associated with cognitive abilities at age 70 or cognitive decline from age 70 to 76. Increased ICA pulsatility and resistivity indices were associated with slower processing speed (both P < 0.001) and worse visuospatial function ( P = 0.036, 0.031, respectively) at age 70, and declining crystallised intelligence from ages 70 to 76 ( P = 0.008, 0.006, respectively). The findings suggest that vascular stiffening, rather than carotid luminal narrowing, adversely influences cognitive ageing and provides a potential target for ameliorating age-related cognitive decline.
Lowthian, Judy A; Straney, Lahn D; Brand, Caroline A; Barker, Anna; Smit, P de Villiers; Newnham, Harvey; Hunter, Peter; Smith, Cathie; Cameron, Peter A
2017-03-01
to profile the trajectory of, and risk factors for, functional decline in older patients in the 30 days following Emergency Department (ED) discharge. prospective cohort study of community-dwelling patients aged ≥65 years, discharged home from a metropolitan Melbourne ED, 31 July 2012 to 30 November 2013. The primary outcome was functional decline, comprising either increased dependency in personal activities of daily living (ADL) or in skills required for living independently instrumental ADL (IADL), deterioration in cognitive function, nursing home admission or death. Univariate analyses were used to select risk factors and logistic regression models constructed to predict functional decline. at 30 days, 34.4% experienced functional decline; with 16.7% becoming more dependent in personal ADL, 17.5% more dependant in IADL and 18.4% suffering deterioration in cognitive function. Factors independently associated with decline were functional impairment prior to the visit in personal ADL (Odds Ratio [OR] 3.21, 95% confidence interval [CI] 2.26-4.53) or in IADL (OR 6.69, 95% CI 4.31-10.38). The relative odds were less for patients with moderately impaired cognition relative to those with normal cognition (OR 0.38, 95% CI 0.19-0.75). There was a 68% decline in the relative odds of functional decline for those with any impairment in IADL who used an aid for mobility (OR 0.32, 95% CI 0.14-0.7). older people with pre-existing ADL impairment were at high risk of functional decline in the 30 days following ED presentation. This effect was largely mitigated for those who used a mobility aid. Early intervention with functional assessments and appropriate implementation of support services and mobility aids could reduce functional decline after discharge. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com
Li, Jun; Cesari, Matteo; Liu, Fei; Dong, Birong; Vellas, Bruno
2017-02-01
Basic and clinical research support a link between diabetes mellitus and Alzheimer disease (AD). However, the relationship with AD progression is unclear. This review focuses on the association between diabetes and cognitive decline in patients with AD. The literature published through May 2015 was searched in 3 databases: PubMed, Embase and Cochrane. Studies evaluating the effects of diabetes on patients with AD or cognitive decline were included, and extracted data were analyzed. A total of 10 articles met the inclusion criteria for review. The results of these studies were inconsistent in terms of the association between diabetes and cognitive decline. Only 2 studies demonstrated that the presence of diabetes was independently related to the progression of cognitive decline in the patients with AD, and 3 studies suggested that histories of diabetes were not correlated with the changes in cognitive function in patients with AD. Half of the included studies even indicated that histories of diabetes were associated with lesser declines in cognitive function in patients with AD. Current evidence indicates that the link between diabetes and cognitive decline in patients with AD is uncertain. Further clinical studies are needed, with larger samples, long-term follow up and an extended battery of cognitive assessments. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.
Luchetti, Martina; Terracciano, Antonio; Stephan, Yannick; Sutin, Angelina R
2016-07-01
Personality traits are associated with risk of dementia; less is known about their association with the trajectory of cognitive functioning. This research examines the association between the 5 major dimensions of personality and cognitive function and decline in older adulthood and includes a meta-analysis of published studies. Personality traits, objective and subjective memory, and cognitive status were collected in a large national sample (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis pooled results from up to 5 prospective studies to examine personality and change in global cognition. Higher Neuroticism was associated with worse performance on all cognitive measures and greater decline in memory, whereas higher Conscientiousness and Openness were associated with better memory performance concurrently and less decline over time. All traits were associated with subjective memory. Higher Conscientiousness and lower Extraversion were associated with better cognitive status and less decline. Although modest, these associations were generally larger than that of hypertension, diabetes, history of psychological treatment, obesity, smoking, and physical inactivity. The meta-analysis supported the association between Neuroticism and Conscientiousness and cognitive decline. Personality is associated with cognitive decline in older adults, with effects comparable to established clinical and lifestyle risk factors. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Role of APOE ε4 Allele and Incident Stroke on Cognitive Decline and Mortality.
Rajan, Kumar B; Aggarwal, Neelum T; Schneider, Julie A; Wilson, Robert S; Everson-Rose, Susan A; Evans, Denis A
2016-01-01
The apolipoprotein E (APOE) ε4 allele and stroke increase the risk of cognitive decline. However, the association of the APOE ε4 allele before and after stroke is not well understood. Using a prospective sample of 3444 (66% African Americans, 61% females, mean age=71.9 y) participants, we examined cognitive decline relative to stroke among those with and without the APOE ε4 allele. In our sample, 505 (15%) had incident stroke. Among participants without stroke, the ε4 allele was associated with increased cognitive decline compared to noncarriers (0.080 vs. 0.036 units/year; P<0.0001). Among participants without the ε4 allele, cognitive decline increased significantly after stroke compared to before stroke (0.115 vs. 0.039 units/year; P<0.0001). Interestingly, cognitive decline before and after stroke was not significantly different among those with the ε4 allele (0.091 vs. 0.102 units/year; P=0.32). Poor cognitive function was associated with higher risk of stroke (hazard ratio=1.41, 95% confidence interval, 1.25-1.58), but the APOE ε4 allele was not (P=0.66). The APOE ε4 allele, cognitive function, and incident stroke were associated with mortality. The association of stroke with cognitive decline appears to differ by the presence of the APOE ε4 allele, but no such interaction was observed for mortality.
Progression of cognitive impairment in stroke/TIA patients over 3 years.
Sachdev, Perminder S; Lipnicki, Darren M; Crawford, John D; Wen, Wei; Brodaty, Henry
2014-12-01
To examine how cognitive deficits progress in the years following a stroke or transient ischaemic attack (TIA). A follow-up study, with neuropsychological and MRI assessments undertaken 3 years after baseline assessments made 3-6 months poststroke in 183 stroke/TIA patients and 97 healthy controls participating in the Sydney Stroke Study. Additional measures included cardiovascular risk factors and apolipoprotein E (APOE) genotype. Stroke/TIA patients had poorer cognitive function and more vascular risk factors than controls at baseline, but did not show greater decline in cognitive function over 3 years except for verbal memory. Patients with a subsequent stroke/TIA showed greater decline in global cognitive function and a number of domains. Rates of incident dementia were 5.9% per year in patients and 0.4% in controls. Both groups showed increased atrophy of the hippocampus, amygdala and whole brain, and an increase in white matter hyperintensities over 3 years; whole brain atrophy was greater in patients. Cognitive decline was greater in women and in those with smaller hippocampi at baseline. For patients without a subsequent stroke/TIA, those with smaller hippocampi or the APOE ε4 allele had greater global cognitive and verbal memory decline. In poststroke patients, cognitive decline was not greater than in comparison subjects, except for verbal memory, unless they had another stroke/TIA. However, dementia incidence was higher in patients, as might be expected from their poorer baseline cognitive functioning. Smaller hippocampi were associated with an increased risk of decline in memory, and APOE ε4 was a risk factor in those without a subsequent stroke/TIA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Konagaya, Yoko; Watanabe, Tomoyuki; Ohta, Toshiki
2012-01-01
The purpose of this study was to evaluate whether physical activities reduce the risk of cognitive decline in community-dwelling elderly. We investigated correlations between cognitive functions at baseline and physical activities, correlations between cognitive functions at baseline and cognitive decline over 4 years, as well as correlations between physical activity at baseline and cognitive decline over 4 years. At baseline, 2,431 community-dwelling elderly completed the cognitive screening by telephone (TICS-J), and answered the questionnaires about physical activities. Of these, 1,040 subjects again completed the TICS-J over 4 years. Physical activities contained moving ability, walking frequency, walking speed, the exercise frequency. At baseline, 870 elderly (age 75.87±4.96 (mean±SD) years, duration of education 11.05±2.41) showed normal cognitive functions and 170 (79.19±6.22, 9.61±2.23) showed cognitive impairment. The total TICS-J score was significantly higher in cognitive normal subjects compared with that of cognitive impaired subjects (36.02±1.89, 30.19±2.25, respectively, p<0.001). Logistic regression analyses showed that moving ability significantly reduced the risk of cognitive impairment in an unadjusted model, and walking speed also reduced the risk of cognitive impairment at baseline even in an adjusted model. Cognitive function at baseline might be a predictor of cognitive function over 4 years. The longitudinal study revealed that walking speed and exercise frequency significantly correlate with maintenance of cognitive function over 4 years. This study provides that physical activities, especially walking speed have significant correlation with cognitive function.
Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa
2015-01-01
Current research suggests that the neuropathology of dementia-including brain changes leading to memory impairment and cognitive decline-is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1-L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a clinical setting.
Torosyan, Nare; Mason, Kelsey; Dahlbom, Magnus; Silverman, Daniel H S
2017-08-01
The aim of this study was to examine the value of fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting subsequent rates of functional and cognitive decline among subjects considered cognitively normal (CN) or clinically diagnosed with mild cognitive impairment (MCI). Analyses of 276 subjects, 92 CN subjects and 184 with MCI, who were enrolled in the Alzheimer's Disease Neuroimaging Initiative, were conducted. Functional decline was assessed using scores on the Functional Activities Questionnaire (FAQ) obtained over a period of 36 months, while cognitive decline was determined using the Alzheimer's disease Assessment Scale-Cognitive subscale (ADAS-Cog) and Mini-Mental State Examination (MMSE) scores. PET images were analyzed using clinically routine brain quantification software. A dementia prognosis index (DPI), derived from a ratio of uptake values in regions of interest known to be hypometabolic in Alzheimer's disease to regions known to be stable, was generated for each baseline FDG-PET scan. The DPI was correlated with change in scores on the neuropsychological examinations to examine the predictive value of baseline FDG-PET. DPI powerfully predicted rate of functional decline among MCI patients (t = 5.75, p < 1.0E-8) and pooled N + MCI patient groups (t = 7.02, p < 1.0E-11). Rate of cognitive decline on MMSE was also predicted by the DPI among MCI (t = 6.96, p < 1.0E-10) and pooled N + MCI (t = 8.78, p < 5.0E-16). Rate of cognitive decline on ADAS-cog was powerfully predicted by the DPI alone among N (p < 0.001), MCI (t = 6.46, p < 1.0E-9) and for pooled N + MCI (t = 8.85, p = 1.1E-16). These findings suggest that an index, derivable from automated regional analysis of brain PET scans, can be used to help predict rates of functional and cognitive deterioration in the years following baseline PET.
Causes, effects and connectivity changes in MS-related cognitive decline.
Rimkus, Carolina de Medeiros; Steenwijk, Martijn D; Barkhof, Frederik
2016-01-01
Cognitive decline is a frequent but undervalued aspect of multiple sclerosis (MS). Currently, it remains unclear what the strongest determinants of cognitive dysfunction are, with grey matter damage most directly related to cognitive impairment. Multi-parametric studies seem to indicate that individual factors of MS-pathology are highly interdependent causes of grey matter atrophy and permanent brain damage. They are associated with intermediate functional effects (e.g. in functional MRI) representing a balance between disconnection and (mal) adaptive connectivity changes. Therefore, a more comprehensive MRI approach is warranted, aiming to link structural changes with functional brain organization. To better understand the disconnection syndromes and cognitive decline in MS, this paper reviews the associations between MRI metrics and cognitive performance, by discussing the interactions between multiple facets of MS pathology as determinants of brain damage and how they affect network efficiency.
Gupta, Vishal K; Winter, Michael; Cabral, Howard; Henault, Lori; Waite, Katherine; Hanchate, Amresh; Bickmore, Timothy W; Wolf, Michael S; Paasche-Orlow, Michael K
2016-08-01
To examine health literacy as a mediator of racial disparities in cognitive decline as measured by executive function in elderly adults. Prospective cohort study. Secondary analysis of ElderWalk trial in Boston, Massachusetts. English-speaking African-American and Caucasian individuals in a walking intervention for community-dwelling adults aged 65 and older without dementia at baseline who completed baseline and 12-month evaluations (N = 198). Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Fluid and crystallized cognitive functions were measured at baseline and 12 months using the Trail-Making Test Part B minus Part B (TMT B-A) and the Controlled Oral Word Association Test (COWAT). Associations between health literacy and 12-month cognitive decline were modeled using multivariate linear regression. Participants with higher health literacy and education experienced less cognitive decline than those with limited health literacy according to the TMT B-A (P = .01). After adjusting for covariates, Caucasian participants (n = 63) experienced less decline than African-American participants (n = 135) on TMT B-A (P = .001) and COWAT (P = .001). Adjusting for health literacy led to a 25.3% decrease in the point estimate for racial difference in TMT B-A and a 19.5% decrease in COWAT. Although independently related to cognitive decline, educational attainment did not mediate racial differences. Health literacy is a partial mediator of racial disparities in cognitive decline. These results indicate the need to develop interventions to mitigate cognitive decline that individuals with low heath literacy can use and to modify the healthcare environment to better accommodate this population. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.
Ben Assayag, Einor; Eldor, Roy; Korczyn, Amos D; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Tene, Oren; Molad, Jeremy; Shapira, Itzhak; Berliner, Shlomo; Volfson, Viki; Shopin, Ludmila; Strauss, Yehuda; Hallevi, Hen; Bornstein, Natan M; Auriel, Eitan
2017-09-01
Type 2 diabetes mellitus (T2DM) is associated with diseases of the brain, kidney, and vasculature. However, the relationship between T2DM, chronic kidney disease, brain alterations, and cognitive function after stroke is unknown. We aimed to evaluate the inter-relationship between T2DM, impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The TABASCO (Tel Aviv brain acute stroke cohort) is a prospective cohort of stroke/transient ischemic attack survivors. The volume and white matter integrity, ischemic lesions, and brain and hippocampal volumes were measured at baseline using 3-T MRI. Cognitive tests were performed on 507 patients, who were diagnosed as having mild cognitive impairment, dementia, or being cognitively intact after 24 months. At baseline, T2DM and impaired renal function (estimated creatinine clearance [eCCl] <60 mL/min) were associated with smaller brain and hippocampal volumes, reduced cortical thickness, and worse white matter microstructural integrity. Two years later, both T2DM and eCCl <60 mL/min were associated with poorer cognitive scores, and 19.7% of the participants developed cognitive decline (mild cognitive impairment or dementia). Multiple analysis, controlling for age, sex, education, and apolipoprotein E4, showed a significant association of both T2DM and eCCl <60 mL/min with cognitive decline. Having both conditions doubled the risk compared with patients with T2DM or eCCl <60 mL/min alone and almost quadrupled the risk compared with patients without either abnormality. T2DM and impaired renal function are independently associated with abnormal brain structure, as well as poorer performance in cognitive tests, 2 years after stroke. The presence of both conditions quadruples the risk for cognitive decline. T2DM and lower eCCl have an independent and additive effect on brain atrophy and the risk of cognitive decline. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691. © 2017 American Heart Association, Inc.
Berendsen, A M; Kang, J H; Feskens, E J M; de Groot, C P G M; Grodstein, F; van de Rest, O
2018-01-01
There is increasing attention for dietary patterns as a potential strategy to prevent cognitive decline. We examined the association between adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and cognitive decline, taking into account the interaction between the apolipoprotein E ε4 genotype and the MIND diet. Population-based prospective cohort study. A total of 16,058 older women aged 70 and over from the Nurses' Health Study. Dietary intake was assessed five times between 1984 and 1998 with a 116-item Food Frequency Questionnaire. The MIND score includes ten brain-healthy foods and five unhealthy foods. Cognition was assessed four times by telephone from 1995 to 2001 (baseline) with the Telephone Interview for Cognitive Status (TICS) and by calculating composite scores of verbal memory and global cognition. Linear regression modelling and linear mixed modelling were used to examine the associations of adherence to the MIND diet with average cognitive function and cognitive change over six years, respectively. Greater long-term adherence to the MIND diet was associated with a better verbal memory score (multivariable-adjusted mean differences between extreme MIND quintiles=0.04 (95%CI 0.01-0.07), p-trend=0.006), but not with cognitive decline over 6 years in global cognition, verbal memory or TICS. Long-term adherence to the MIND diet was moderately associated with better verbal memory in later life. Future studies should address this association within populations at greater risk of cognitive decline.
Zhang, Zhou; Zhang, Bing; Wang, Xin; Zhang, Xin; Yang, Qing X; Qing, Zhao; Lu, Jiaming; Bi, Yan; Zhu, Dalong
2018-05-01
Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. © 2018 by the American Diabetes Association.
Kirova, Anna-Mariya; Bays, Rebecca B; Lagalwar, Sarita
2015-01-01
Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.
Yau, Suk-yu; Christie, Brian R.; So, Kwok-fai
2014-01-01
Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. PMID:24818140
Zeki Al Hazzouri, Adina; Haan, Mary N; Osypuk, Theresa; Abdou, Cleopatra; Hinton, Ladson; Aiello, Allison E
2011-08-15
In 1 previous study, it was shown that neighborhood socioeconomic disadvantage is associated with cognitive decline among Latinos. No studies have explored whether and to what extent individual-level socioeconomic factors account for the relation between neighborhood disadvantage and cognitive decline. The purpose of the present study was to assess the influence of neighborhood socioeconomic position (SEP) on cognitive decline and examine how individual-level SEP factors (educational level, annual income, and occupation) influenced neighborhood associations over the course of 10 years. Participants (n = 1,789) were community-dwelling older Mexican Americans from the Sacramento Area Latino Study on Aging. Neighborhood SEP was derived by linking the participant's individual data to the 2000 decennial census. The authors assessed cognitive function with the Modified Mini-Mental State Examination. Analyses used 3-level hierarchical linear mixed models of time within individuals within neighborhoods. After adjustment for individual-level sociodemographic characteristics, higher neighborhood SEP was significantly associated with cognitive function (β = -0.033; P < 0.05) and rates of decline (β = -0.0009; P < 0.10). After adjustment for individual educational level, neighborhood SEP remained associated with baseline cognition but not with rates of decline. Differences in individual educational levels explained most of the intra- and interneighborhood variance. These results suggest that the effect of neighborhood SEP on cognitive decline among Latinos is primarily accounted for by education.
Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M L
2017-01-01
Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young ( n = 40, mean age = 23.1 ± 2.6 years) and older adults ( n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age.
Incident lacunes influence cognitive decline: the LADIS study.
Jokinen, H; Gouw, A A; Madureira, S; Ylikoski, R; van Straaten, E C W; van der Flier, W M; Barkhof, F; Scheltens, P; Fazekas, F; Schmidt, R; Verdelho, A; Ferro, J M; Pantoni, L; Inzitari, D; Erkinjuntti, T
2011-05-31
In cerebral small vessel disease, the core MRI findings include white matter lesions (WML) and lacunar infarcts. While the clinical significance of WML is better understood, the contribution of lacunes to the rate of cognitive decline has not been established. This study investigated whether incident lacunes on MRI determine longitudinal cognitive change in elderly subjects with WML. Within the Leukoaraiosis and Disability Study (LADIS), 387 subjects were evaluated with repeated MRI and neuropsychological assessment at baseline and after 3 years. Predictors of change in global cognitive function and specific cognitive domains over time were analyzed with multivariate linear regression. After controlling for demographic factors, baseline cognitive performance, baseline lacunar and WML lesion load, and WML progression, the number of new lacunes was related to subtle decrease in compound scores for executive functions (p = 0.021) and speed and motor control (p = 0.045), but not for memory or global cognitive function. Irrespective of lacunes, WML progression was associated with decrease in executive functions score (p = 0.016). Incident lacunes on MRI parallel a steeper rate of decline in executive functions and psychomotor speed. Accordingly, in addition to WML, lacunes determine longitudinal cognitive impairment in small vessel disease. Although the individual contribution of lacunes on cognition was modest, they cannot be considered benign findings, but indicate a risk of progressive cognitive impairment.
Chen, S; Honda, T; Narazaki, K; Chen, T; Kishimoto, H; Haeuchi, Y; Kumagai, S
2018-01-01
To assess the relationship between physical frailty and subsequent decline in global cognitive function in the non-demented elderly. A prospective population-based study in a west Japanese suburban town, with two-year follow-up. Community-dwellers aged 65 and older without placement in long-term care, and not having a history of dementia, Parkinson's disease and depression at baseline, who participated in the cohort of the Sasaguri Genkimon Study and underwent follow-up assessments two years later (N = 1,045). Global cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Physical frailty was identified according to the following five components: weight loss, low grip strength, exhaustion, slow gait speed and low physical activities. Linear regression models were used to examine associations between baseline frailty status and the MoCA scores at follow-up. Logistic regression models were used to estimate the risk of cognitive decline (defined as at least two points decrease of MoCA score) according to baseline frailty status. Seven hundred and eight non-demented older adults were included in the final analyses (mean age: 72.6 ± 5.5 years, male 40.3%); 5.8% were frail, and 40.8% were prefrail at baseline. One hundred and fifty nine (22.5%) participants experienced cognitive decline over two years. After adjustment for baseline MoCA scores and all confounders, being frail at baseline was significantly associated with a decline of 1.48 points (95% confidence interval [CI], -2.37 to -0.59) in MoCA scores, as compared with non-frailty. Frail persons were over two times more likely to experience cognitive decline (adjusted odds ratio 2.28; 95% CI, 1.02 to 5.08), compared to non-frail persons. Physical frailty is associated with longitudinal decline in global cognitive function in the non-demented older adults over a period of two years. Physically frail older community-dwellers should be closely monitored for cognitive decline that can be sensitively captured by using the MoCA.
Cranial Radiation Therapy and Damage to Hippocampal Neurogenesis
ERIC Educational Resources Information Center
Monje, Michelle
2008-01-01
Cranial radiation therapy is associated with a progressive decline in cognitive function, prominently memory function. Impairment of hippocampal neurogenesis is thought to be an important mechanism underlying this cognitive decline. Recent work has elucidated the mechanisms of radiation-induced failure of neurogenesis. Potential therapeutic…
Education and the cognitive decline associated with MRI-defined brain infarct.
Elkins, J S; Longstreth, W T; Manolio, T A; Newman, A B; Bhadelia, R A; Johnston, S C
2006-08-08
To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct. The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI. In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others (p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI-defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others (6.3, 95% CI 4.4- to 8.2-point decline vs 1.7, 95% CI 0.7- to 2.7-point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI-defined infarct. Education seems to modify an individual's decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain.
High-sensitivity C-reactive protein and cognitive decline: the English Longitudinal Study of Ageing.
Zheng, Fanfan; Xie, Wuxiang
2018-06-01
High-sensitivity C-reactive protein (hs-CRP) has been suggested to be involved in the process of cognitive decline. However, the results from previous studies exploring the relationship between hs-CRP concentration and cognitive decline are inconsistent. We employed data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing. Cognitive function was assessed at baseline (wave 2) and reassessed biennially at waves 3-7. A total of 5257 participants (54.9% women, mean age 65.4 ± 9.4 years) with baseline hs-CRP levels ranged from 0.2 to 210.0 mg/L (median: 2.0 mg/L, interquartile range: 0.9-4.1 mg/L) were studied. The mean follow-up duration was 8.1 ± 2.8 years, and the mean number of cognitive assessment was 4.9 ± 1.5. Linear mixed models show that a one-unit increment in natural log-transformed hs-CRP was associated with faster declines in global cognitive scores [-0.048 points/year, 95% confidence interval (CI) -0.072 to -0.023], memory scores (-0.022 points/year, 95% CI -0.031 to -0.013), and executive function scores (-0.025 points/year, 95% CI -0.043 to -0.006), after multivariable adjustment. Compared with the lowest quartile of hs-CRP, the multivariable-adjusted rate of global cognitive decline associated with the second, third, and highest quartile was faster by -0.043 points/year (95% CI -0.116 to 0.029), -0.090 points/year (95% CI -0.166 to -0.015), -0.145 (95% CI -0.221 to -0.069), respectively (p for trend <0.001). Similarly, memory and executive function also declined faster with increasing quartiles of hs-CRP. A significant association between hs-CRP concentration and long-term cognitive decline was observed in this study. Hs-CRP might serve as a biomarker for cognitive decline.
Hessen, Erik; Nordlund, Arto; Stålhammar, Jacob; Eckerström, Marie; Bjerke, Maria; Eckerström, Carl; Göthlin, Mattias; Fladby, Tormod; Reinvang, Ivar; Wallin, Anders
2015-01-01
There is a need to find very early markers for pre-clinical Alzheimer's disease as interventions early in the disease process are thought to be most effective. The present study aimed to address the potential relation between cerebrospinal fluid (CSF) biomarkers and reduced cognitive function in a relatively young cohort of memory clinic patients with subjective cognitive decline. 122 patients (mean age 63 years) with subjective cognitive decline were recruited from two university memory clinics and followed for two years. The main finding was that the subgroup with objective memory decline during the study period had significantly higher T-tau at baseline than the group with improved memory. Baseline CSF variables showed a trend toward more pathological values in the patients with memory decline compared to those who improved or remained stable. The baseline memory score of those who declined was significantly better than the baseline score of those who improved over two years. The general trend for the whole group was improved memory and executive test scores. There were no differences in cognitive scores based on CSF quartiles at baseline, nor were there differences in cognitive outcome for patients with early amnestic mild cognitive impairment versus average cognitive function at baseline. The main finding that T-tau rather than amyloid-β was associated with memory decline do not support the prevailing opinion about the chain of events assumed to take place in Alzheimer's disease. In addition, memory decline was not associated with poor baseline memory score. Thus, a memory cut-off indicating low baseline memory would not would have identified the declining group.
Characteristic of cognitive decline in Parkinson's disease: a 1-year follow-up.
McKinlay, Audrey; Grace, Randolph C
2011-10-01
The aim of this study was to track the evolution of cognitive decline in Parkinson's disease (PD) patients 1 year after baseline testing. Thirty-three PD patients, divided according to three previously determined subgroups based on their initial cognitive performance, and a healthy comparison group were reassessed after a 1-year interval. Participants were assessed in the following five domains: Executive Function, Problem Solving, Working Memory/Attention, Memory, and Visuospatial Ability. The PD groups differed on the domains of Executive Function, Problem Solving, and Working Memory, with the most severe deficits being evident for the group that had previously shown the greatest level of impairment. Increased cognitive problems were also associated with decreased functioning in activities of daily living. The most severely impaired group had evidence of global cognitive decline, possibly reflecting a stage of preclinical dementia.
López-Higes, Ramón; Martín-Aragoneses, María T; Rubio-Valdehita, Susana; Delgado-Losada, María L; Montejo, Pedro; Montenegro, Mercedes; Prados, José M; de Frutos-Lucas, Jaisalmer; López-Sanz, David
2018-01-01
The present study explores the role of cognitive reserve, executive functions, and working memory (WM) span, as factors that might explain training outcomes in cognitive status. Eighty-one older adults voluntarily participated in the study, classified either as older adults with subjective cognitive decline or cognitively intact. Each participant underwent a neuropsychological assessment that was conducted both at baseline (entailing cognitive reserve, executive functions, WM span and depressive symptomatology measures, as well as the Mini-Mental State Exam regarding initial cognitive status), and then 6 months later, once each participant had completed the training program (Mini-Mental State Exam at the endpoint). With respect to cognitive status the training program was most beneficial for subjective cognitive decline participants with low efficiency in inhibition at baseline (explaining a 33% of Mini-Mental State Exam total variance), whereas for cognitively intact participants training gains were observed for those who presented lower WM span.
Serum phosphate and cognitive function in older men.
Slinin, Yelena; Vo, Tien; Taylor, Brent C; Murray, Anne M; Schousboe, John; Langsetmo, Lisa; Ensrud, Kristine
2018-01-01
Determine whether serum phosphate is associated with concurrent cognitive impairment and subsequent cognitive decline in older men independent of demographic covariates and atherosclerotic risk factors. In a prospective study of 5529 men enrolled in the Osteoporotic Fractures in Men study, we measured baseline serum phosphate, baseline cognitive function, and change in cognitive function between baseline and follow-up exams an average of 4.6 years later using the Modified Mini-Mental State (3MS) Examination and Trails B. There was no association between serum phosphate and odds of cognitive impairment as assessed by baseline 3MS score or risk of cognitive decline as assessed by longitudinal change in 3MS score. Higher baseline serum phosphate was associated with higher odds of poor executive function as assessed by Trails B with fully adjusted odds ratios 1.12 (95% confidence interval: 0.83-1.52), 1.31 (0.97-1.77), and 1.45 (1.08-1.94) for men in the second, third, and fourth versus the bottom quartile (referent group) of serum phosphate (p-trend 0.007). However, higher phosphate level was not associated with risk of decline in executive function as assessed by longitudinal change in Trails B score with fully adjusted odds ratios 0.94 (95% confidence interval 0.69-1.28), 0.96 (0.70-1.32), and 1.21 (0.89-1.66) for men in the second, third, and fourth versus the bottom quartile (referent group) of serum phosphate (p-trend 0.22). Higher serum phosphate in older men was associated with a higher likelihood of poor executive function, but not with impaired global cognitive function or decline in executive or global cognition. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.
Brown, Paul D.; Pugh, Stephanie; Laack, Nadia N.; Wefel, Jeffrey S.; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H.; Roberge, David; Kavadi, Vivek; Bentzen, Soren M.; Mehta, Minesh P.; Watkins-Bruner, Deborah
2013-01-01
Background To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Methods Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Results Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62–0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Conclusions Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852. PMID:23956241
Brown, Paul D; Pugh, Stephanie; Laack, Nadia N; Wefel, Jeffrey S; Khuntia, Deepak; Meyers, Christina; Choucair, Ali; Fox, Sherry; Suh, John H; Roberge, David; Kavadi, Vivek; Bentzen, Soren M; Mehta, Minesh P; Watkins-Bruner, Deborah
2013-10-01
To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT). Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed. Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks. Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.
Guo, Shan-Shan; Gao, Xiao-Fang; Gu, Yan-Rong
2016-01-01
Maca has been used as a foodstuff and a traditional medicine in the Andean region for over 2,000 years. Recently the neuroprotective effects of maca also arouse interest of researchers. Decrease in mitochondrial function and decline in autophagy signaling may participate in the process of age-related cognitive decline. This study aimed to investigate if maca could improve cognitive function of middle-aged mice and if this effect was associated with improvement of mitochondrial activity and modulation of autophagy signaling in mouse cortex. Fourteen-month-old male ICR mice received maca powder administered by gavage for five weeks. Maca improved cognitive function, motor coordination, and endurance capacity in middle-aged mice, accompanied by increased mitochondrial respiratory function and upregulation of autophagy-related proteins in cortex. Our findings suggest that maca is a newly defined nutritional plant which can improve mitochondrial function and upregulate autophagy-related proteins and may be an effective functional food for slowing down age-related cognitive decline. PMID:27648102
Guo, Shan-Shan; Gao, Xiao-Fang; Gu, Yan-Rong; Wan, Zhong-Xiao; Lu, A-Ming; Qin, Zheng-Hong; Luo, Li
2016-01-01
Maca has been used as a foodstuff and a traditional medicine in the Andean region for over 2,000 years. Recently the neuroprotective effects of maca also arouse interest of researchers. Decrease in mitochondrial function and decline in autophagy signaling may participate in the process of age-related cognitive decline. This study aimed to investigate if maca could improve cognitive function of middle-aged mice and if this effect was associated with improvement of mitochondrial activity and modulation of autophagy signaling in mouse cortex. Fourteen-month-old male ICR mice received maca powder administered by gavage for five weeks. Maca improved cognitive function, motor coordination, and endurance capacity in middle-aged mice, accompanied by increased mitochondrial respiratory function and upregulation of autophagy-related proteins in cortex. Our findings suggest that maca is a newly defined nutritional plant which can improve mitochondrial function and upregulate autophagy-related proteins and may be an effective functional food for slowing down age-related cognitive decline.
Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Gamble, Keith; Buchman, Aron S.; Bennett, David A.
2012-01-01
Objective Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment. Methods Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams. Results Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p’s<0.001). Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment). Conclusions Poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment, those widely considered “cognitively healthy.” These findings suggest that even very subtle age-related changes in cognition have detrimental effects on judgment. PMID:22916287
Midlife C-reactive protein and risk of cognitive decline: a 31-year follow-up.
Laurin, Danielle; David Curb, J; Masaki, Kamal H; White, Lon R; Launer, Lenore J
2009-11-01
There is evidence for a relationship between raised inflammatory markers, including high sensitivity C-reactive protein (hs-CRP), measured late in life, and an increased risk of cognitive decline and dementia. This study evaluates the association of midlife hs-CRP concentrations with late-life longitudinal trends in cognitive function. Data are from the Honolulu-Asia Aging Study (HAAS), a longitudinal community-based study of Japanese American men. hs-CRP levels were measured on average 25 years before cognitive testing began in 1991. Subjects were followed from up to three follow-up examinations (mean of 6.1 years). At each exam, cognitive function was measured with the Cognitive Abilities Screening Instrument (CASI). This analysis includes a sub-sample of 691 subjects dementia-free in 1991. With incident dementia cases included, those with the highest quartile of hs-CRP had significantly more cognitive decline than those in the lowest quartile, after adjustment for baseline CASI score, demographic and cardiovascular risk factors. When cases were removed, there was no difference in cognitive decline by CRP quartile. This relationship was not modified by the presence of apolipoprotein E varepsilon4. These findings suggest that inflammatory mechanisms during midlife may reflect underlying processes contributing to dementia-related cognitive decline late in life.
Pietrzak, Robert H; Lim, Yen Ying; Neumeister, Alexander; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Restrepo, Carolina; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul
2015-03-01
Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms. To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD. In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline. These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.
Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M. L.
2017-01-01
Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young (n = 40, mean age = 23.1 ± 2.6 years) and older adults (n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age. PMID:28928653
Rickenbach, Elizabeth H.; Almeida, David M.; Seeman, Teresa E.; Lachman, Margie E.
2014-01-01
We examined whether long-term fluid cognitive decline was associated with memory problems in everyday life, and whether stress plays a moderating role. We expected that the association between cognitive decline and everyday memory problems would be magnified in the context of self-reported and physiological stress. Data are from the Boston Longitudinal Study, a subsample of the Midlife in the United States study. Participants in the current study (n=112) completed a battery of tests measuring fluid cognitive functioning at Time 1 (T1) and 2 (T2) over ten years. At T2, participants completed weekly diaries of self-reported daily stressors and everyday memory problems for twelve consecutive weeks. Also at T2, participants provided four saliva samples over the course of one day to assess physiological stress using diurnal cortisol profiles [cortisol awakening response (CAR) and diurnal cortisol slope (DCS)]. Self-reported daily stressors and a less healthy DCS were associated with more everyday memory problems, and participants with greater cognitive decline reported more memory problems compared to those with less or no decline. Self-reported daily stressors and CAR moderated the relationship of cognitive decline and memory problems. As expected, more cognitive decline was associated with greater increases in memory problems on weeks when individuals reported more daily stressors and for individuals with a less healthy CAR. The current findings can inform interventions aimed to identify factors, such as daily stress, that contribute to daily functioning in the context of cognitive decline. PMID:25365691
McCaddon, Andrew; Miller, Joshua W
2015-10-01
Hyperhomocysteinemia is a recognized risk factor for cognitive decline and incident dementia in older adults. Two recent reports addressed the cumulative epidemiological evidence for this association but expressed conflicting opinions. Here, the evidence is reviewed in relation to Sir Austin Bradford Hill's criteria for assessing "causality," and the latest meta-analysis of the effects of homocysteine-lowering on cognitive function is critically examined. The meta-analysis included 11 trials, collectively assessing 22,000 individuals, that examined the effects of B vitamin supplements (folic acid, vitamin B12, vitamin B6) on global or domain-specific cognitive decline. It concluded that homocysteine-lowering with B vitamin supplements has no significant effect on cognitive function. However, careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine-lowering on cognitive decline, since the trials typically did not include individuals who were experiencing such decline. Further definitive trials in older adults experiencing cognitive decline are still urgently needed. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara
2017-06-01
Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging. Copyright © 2017 Elsevier Inc. All rights reserved.
Lower Limb Function in Elderly Korean Adults Is Related to Cognitive Function.
Kim, A-Sol; Ko, Hae-Jin
2018-05-01
Patients with cognitive impairment have decreased lower limb function. Therefore, we aimed to investigate the relationship between lower limb function and cognitive disorders to determine whether lower limb function can be screened to identify cognitive decline. Using Korean National Health Insurance Service-National Sample Cohort database data, we assessed the cognitive and lower limb functioning of 66-year-olds who underwent national health screening between 2010 and 2014. Cognitive function was assessed via a questionnaire. Timed Up-and-Go (TUG) and one-leg-standing (OLS) tests were performed to evaluate lower limb function. Associations between cognitive and lower limb functions were analyzed, and optimal cut-off points for these tests to screen for cognitive decline, were determined. Cognitive function was significantly correlated with TUG interval ( r = 0.414, p < 0.001) and OLS duration ( r = −0.237, p < 0.001). Optimal cut-off points for screening cognitive disorders were >11 s and ≤12 s for TUG interval and OLS duration, respectively. Among 66-year-olds who underwent national health screening, a significant correlation between lower limb and cognitive function was demonstrated. The TUG and OLS tests are useful screening tools for cognitive disorders in elderly patients. A large-scale prospective cohort study should be conducted to investigate the causal relationship between cognitive and lower limb function.
Noguchi-Shinohara, Moeko; Abe, Chiemi; Yuki-Nozaki, Sohshi; Dohmoto, Chiaki; Mori, Ayaka; Hayashi, Koji; Shibata, Syutaro; Ikeda, Yoshihisa; Sakai, Kenji; Iwasa, Kazuo; Yokogawa, Masami; Ishimiya, Mai; Nakamura, Hiroyuki; Yokoji, Hidehiro; Komai, Kiyonobu; Nakamura, Hiroyuki; Yamada, Masahito
2018-05-11
Antioxidants like vitamins C and E may minimize the risk for Alzheimer's disease. We examined whether vitamins C and E modify the apolipoprotein E (APOE) E4-related risks for developing cognitive decline. We conducted a population-based prospective study including Japanese residents aged 65 years from Nakajima, Japan. The participants received an evaluation of cognitive function and underwent blood tests including tests for vitamins C and E levels and APOE phenotypes. The APOE E4-by-gender-by-vitamin C or E interactions on developing cognitive decline were analyzed. Of 606 participants with normal cognitive function determined using a baseline survey (2007-2008), 349 completed the follow up survey between 2014 and 2016. In women with APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin C concentration tertile [multivariate OR 0.10 (95% CI 0.01-0.93)] compared with the lowest tertile. In men without APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin E concentration tertile [multivariate OR 0.19 (0.05-0.74)] as compared with the lowest tertile. Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.
Cognitive decline following incident and preexisting diabetes mellitus in a population sample.
Rajan, Kumar B; Arvanitakis, Zoe; Lynch, Elizabeth B; McAninch, Elizabeth A; Wilson, Robert S; Weuve, Jennifer; Barnes, Lisa L; Bianco, Antonio C; Evans, Denis A
2016-10-18
To examine if incident and preexisting diabetes mellitus (DM) were associated with cognitive decline among African Americans (AAs) and European Americans (EAs). Based on a prospective study of 7,740 older adults (mean age 72.3 years, 64% AA, 63% female), DM was ascertained by hypoglycemic medication use and Medicare claims during physician or hospital visits, and cognition by performance on a brief battery for executive functioning, episodic memory, and Mini-Mental State Examination (MMSE). Decline in composite and individual tests among those with incident DM, with preexisting DM, and without DM was studied using a linear mixed effects model with and without change point. At baseline, 737 (15%) AAs and 269 (10%) EAs had preexisting DM. Another 721 (17%) AAs and 289 (12%) EAs had incident DM in old age. Following incident DM, cognitive decline increased by 36% among AAs and by 40% among EAs compared to those without DM. No significant difference was observed between AAs and EAs (p = 0.64). However, cognitive decline increased by 17% among AAs with preexisting DM compared to those without DM, but no increased decline was observed among EAs with preexisting DM. In secondary analyses, faster decline in executive functioning and episodic memory was observed following incident DM. In old age, faster cognitive decline was present among AAs and EAs following incident DM, compared to cognitive decline prior to DM, and among those without DM. This underscores the need for stronger prevention and control of DM in old age. © 2016 American Academy of Neurology.
Toyama, Kensuke; Sugiyama, Seigo; Oka, Hideki; Hamada, Mari; Iwasaki, Yuri; Horio, Eiji; Rokutanda, Taku; Nakamura, Shinichi; Spin, Joshua M; Tsao, Philip S; Ogawa, Hisao
2017-01-01
Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline.
Education and Cognitive Decline in Older Americans: Results From the AHEAD Sample
Alley, Dawn; Suthers, Kristen; Crimmins, Eileen
2009-01-01
Although education is consistently related to better cognitive performance, findings on the relationship between education and age-associated cognitive change have been conflicting. Using measures of multiple cognitive domains from four waves of the Asset and Health Dynamics of the Oldest Old study, a representative sample of Americans aged 70 years and older, the authors performed growth curve modeling to examine the relationships between education, initial cognitive score, and the rate of decline in cognitive function. More years of education were linked to better initial performance on each of the cognitive tests, and higher levels of education were linked to slower decline in mental status. However, more education was unrelated to the rate of decline in working memory, and education was associated with somewhat faster cognitive decline on measures of verbal memory. These findings highlight the role of early-life experiences not only in long-term cognitive performance but also in old-age cognitive trajectories. PMID:19830260
John, A; Patel, U; Rusted, J; Richards, M; Gaysina, D
2018-05-24
Evidence suggests that affective problems, such as depression and anxiety, increase risk for late-life dementia. However, the extent to which affective problems influence cognitive decline, even many years prior to clinical diagnosis of dementia, is not clear. The present study systematically reviews and synthesises the evidence for the association between affective problems and decline in cognitive state (i.e., decline in non-specific cognitive function) in older adults. An electronic search of PubMed, PsycInfo, Cochrane, and ScienceDirect was conducted to identify studies of the association between depression and anxiety separately and decline in cognitive state. Key inclusion criteria were prospective, longitudinal designs with a minimum follow-up period of 1 year. Data extraction and methodological quality assessment using the STROBE checklist were conducted independently by two raters. A total of 34 studies (n = 71 244) met eligibility criteria, with 32 studies measuring depression (n = 68 793), and five measuring anxiety (n = 4698). A multi-level meta-analysis revealed that depression assessed as a binary predictor (OR 1.36, 95% CI 1.05-1.76, p = 0.02) or a continuous predictor (B = -0.008, 95% CI -0.015 to -0.002, p = 0.012; OR 0.992, 95% CI 0.985-0.998) was significantly associated with decline in cognitive state. The number of anxiety studies was insufficient for meta-analysis, and they are described in a narrative review. Results of the present study improve current understanding of the temporal nature of the association between affective problems and decline in cognitive state. They also suggest that cognitive function may need to be monitored closely in individuals with affective disorders, as these individuals may be at particular risk of greater cognitive decline.
DOT National Transportation Integrated Search
2016-04-01
A significant factor impinging on older drivers ability to maintain safe and efficient mobility as : they age is the decline in behavioral, cognitive, and perceptual functions. Declines in vision, : hearing, cognitive processing, physical strength...
Mundell, Niamh L; Daly, Robin M; Macpherson, Helen; Fraser, Steve F
2017-04-01
Androgen deprivation therapy (ADT) is an effective and widely prescribed treatment for prostate cancer (PCa), but it is associated with multiple treatment-induced adverse effects that impact on various musculoskeletal and cardiometabolic health outcomes. Emerging research has shown that ADT is also associated with cognitive impairment, which has been linked to a loss of independence, increased falls and fracture risk and greater use of medical services. The aim of this review is to outline the evidence related to the effect of ADT use on cognitive function, and propose a role for exercise training as part of usual care to prevent and/or manage cognitive impairments for PCa survivors on ADT. The following results have been obtained from this study. ADT has been shown to adversely affect specific cognitive domains, particularly verbal memory, visuomotor function, attention and executive function. However, current clinical guidelines do not recommend routine assessment of cognitive function in these men. No studies have examined whether exercise training can preserve or improve cognitive function in these men, but in healthy adults', multimodal exercise training incorporating aerobic training, progressive resistance training (PRT) and challenging motor control exercises have the potential to attenuate cognitive decline. In conclusion, as treatment with ADT for men with PCa has been associated with a decline in cognition, it is recommended that cognitive function be routinely monitored in these men and that regular exercise training be prescribed to preserve (or improve) cognitive function. Assessment of cognition and individualised exercise training should be considered in the usual treatment plan of PCa patients receiving ADT. © 2017 Society for Endocrinology.
Functional Trajectories, Cognition, and Subclinical Cerebrovascular Disease.
Dhamoon, Mandip S; Cheung, Ying-Kuen; Gutierrez, Jose; Moon, Yeseon P; Sacco, Ralph L; Elkind, Mitchell S V; Wright, Clinton B
2018-03-01
Cognition and education influence functional trajectories, but whether associations differ with subclinical brain infarcts (SBI) or white matter hyperintensity volume (WMHV) is unknown. We hypothesized that SBI and WMHV moderated relationships between cognitive performance and education and functional trajectories. A total of 1290 stroke-free individuals underwent brain magnetic resonance imaging and were followed for 7.3 years (mean) with annual functional assessments with the Barthel index (range, 0-100). Magnetic resonance imaging measurements included pathology-informed SBI (PI-SBI) and WMHV (% total cranial volume). Generalized estimating equation models tested associations between magnetic resonance imaging variables and baseline Barthel index and change in Barthel index, adjusting for demographic, vascular, cognitive, and social risk factors, and stroke and myocardial infarction during follow-up. We tested interactions among education level, baseline cognitive performance (Mini-Mental State score), and functional trajectories and ran models stratified by levels of magnetic resonance imaging variables. Mean age was 70.6 (SD, 9.0) years; 19% had PI-SBI, and mean WMHV was 0.68%. Education did not modify associations between cognition and functional trajectories. PI-SBI modified associations between cognition and functional trajectories ( P =0.04) with a significant protective effect of better cognition on functional decline seen only in those without PI-SBI. There was no significant interaction for WMHV ( P =0.8). PI-SBI, and greater WMHV, were associated with 2- to 3-fold steeper functional decline, holding cognition constant. PI-SBI moderated the association between cognition and functional trajectories, with 3-fold greater decline among those with PI-SBI (compared with no PI-SBI) and normal baseline cognition. This highlights the strong and independent association between subclinical markers and patient-centered trajectories over time. © 2018 American Heart Association, Inc.
Verfaillie, Sander C J; Slot, Rosalinde E; Tijms, Betty M; Bouwman, Femke; Benedictus, Marije R; Overbeek, Jozefien M; Koene, Teddy; Vrenken, Hugo; Scheltens, Philip; Barkhof, Frederik; van der Flier, Wiesje M
2018-01-01
We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2-8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini-Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [β (SE) = 0.20 (0.07)], temporal [β (SE) = 0.18 (0.07)], and occipital [β (SE) = 0.22 (0.09)] cortices (all p < 0.05 FDR ). These findings illustrate that early cortical changes, particularly in the temporal cortex, herald incipient cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.
Burfeind, Kevin G; Murchison, Charles F; Westaway, Shawn K; Simon, Matthew J; Erten-Lyons, Deniz; Kaye, Jeffrey A; Quinn, Joseph F; Iliff, Jeffrey J
2017-09-01
The glymphatic system is a brain-wide perivascular network that facilitates clearance of proteins, including amyloid β, from the brain interstitium through the perivascular exchange of cerebrospinal fluid and interstitial fluid. The astrocytic water channel aquaporin-4 (AQP4) is required for glymphatic system function, and impairment of glymphatic function in the aging brain is associated with altered AQP4 expression and localization. In human cortical tissue, alterations in AQP4 expression and localization are associated with Alzheimer's disease (AD) status and pathology. Although this suggests a potential role for AQP4 in the development or progression of AD, the relationship between of naturally occurring variants in the human AQP4 gene and cognitive function has not yet been evaluated. Using data from several longitudinal aging cohorts, we investigated the association between five AQP4 single-nucleotide polymorphisms (SNPs) and the rate of cognitive decline in participants with a diagnosis of AD. None of the five SNPs were associated with different rates of AD diagnosis, age of dementia onset in trial subjects. No association between AQP4 SNPs with histological measures of AD pathology, including Braak stage or neuritic plaque density was observed. However, AQP4 SNPs were associated with altered rates of cognitive decline after AD diagnosis, with two SNPS (rs9951307 and rs3875089) associated with slower cognitive decline and two (rs3763040 and rs3763043) associated with more rapid cognitive decline after AD diagnosis. These results provide the first evidence that variations in the AQP4 gene, whose gene product AQP4 is vital for glymphatic pathway function, may modulate the progression of cognitive decline in AD.
Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort.
Mecca, Adam P; Michalak, Hannah R; McDonald, Julia W; Kemp, Emily C; Pugh, Erika A; Becker, Melinda L; Mecca, Marcia C; van Dyck, Christopher H
2018-06-08
We investigated the relationship between sleep disturbance and cognitive decline or clinical conversion in individuals with normal cognition (CN), as well as those with mild cognitive impairment (MCI) and dementia due to Alzheimer disease (AD-dementia). Secondary analysis of 1,629 adults between 48 and 91 years of age with up to 24 months of follow-up from the ADNI (Alzheimer's Disease Neuroimaging Initiative), a longitudinal cohort study. Sleep disturbance was not associated with decline in memory, executive function, or global cognition. The presence of sleep disturbance did not significantly increase the risk of diagnostic conversion in CN, early MCI, or late MCI participants. This study investigated the effect of sleep disturbance on cognitive decline using several outcomes and does not support the hypothesis that sleep disturbance predicts subsequent cognitive decline. © 2018 S. Karger AG, Basel.
BioAge: Toward A Multi-Determined, Mechanistic Account of Cognitive Aging
DeCarlo, Correne A.; Tuokko, Holly A.; Williams, Dorothy; Dixon, Roger A.; MacDonald, Stuart W.S.
2014-01-01
The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. PMID:25278166
BioAge: toward a multi-determined, mechanistic account of cognitive aging.
DeCarlo, Correne A; Tuokko, Holly A; Williams, Dorothy; Dixon, Roger A; MacDonald, Stuart W S
2014-11-01
The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline. Copyright © 2014 Elsevier B.V. All rights reserved.
The Dynamic Relationship Between Physical Function and Cognition in Longitudinal Aging Cohorts
Clouston, Sean A. P.; Brewster, Paul; Kuh, Diana; Richards, Marcus; Cooper, Rachel; Hardy, Rebecca; Rubin, Marcie S.; Hofer, Scott M.
2013-01-01
On average, older people remember less and walk more slowly than do younger persons. Some researchers argue that this is due in part to a common biologic process underlying age-related declines in both physical and cognitive functioning. Only recently have longitudinal data become available for analyzing this claim. We conducted a systematic review of English-language research published between 2000 and 2011 to evaluate the relations between rates of change in physical and cognitive functioning in older cohorts. Physical functioning was assessed using objective measures: walking speed, grip strength, chair rise time, flamingo stand time, and summary measures of physical functioning. Cognition was measured using mental state examinations, fluid cognition, and diagnosis of impairment. Results depended on measurement type: Change in grip strength was more strongly correlated with mental state, while change in walking speed was more strongly correlated with change in fluid cognition. Examining physical and cognitive functioning can help clinicians and researchers to better identify individuals and groups that are aging differently and at different rates. In future research, investigators should consider the importance of identifying different patterns and rates of decline, examine relations between more diverse types of measures, and analyze the order in which age-related declines occur. PMID:23349427
Human Neural Stem Cell Transplantation Ameliorates Radiation-Induced Cognitive Dysfunction
Acharya, Munjal M.; Christie, Lori-Ann; Lan, Mary L.; Giedzinski, Erich; Fike, John R.; Rosi, Susanna; Limoli, Charles L.
2012-01-01
Cranial radiotherapy induces progressive and debilitating declines in cognition that may, in part, be caused by the depletion of neural stem cells. The potential of using stem cell replacement as a strategy to combat radiation-induced cognitive decline was addressed by irradiating athymic nude rats followed 2 days later by intrahippocampal transplantation with human neural stem cells (hNSC). Measures of cognitive performance, hNSC survival, and phenotypic fate were assessed at 1 and 4 months after irradiation. Irradiated animals engrafted with hNSCs showed significantly less decline in cognitive function than irradiated, sham-engrafted animals and acted indistinguishably from unirradiated controls. Unbiased stereology revealed that 23% and 12% of the engrafted cells survived 1 and 4 months after transplantation, respectively. Engrafted cells migrated extensively, differentiated along glial and neuronal lineages, and expressed the activity-regulated cytoskeleton-associated protein (Arc), suggesting their capability to functionally integrate into the hippocampus. These data show that hNSCs afford a promising strategy for functionally restoring cognition in irradiated animals. PMID:21757460
Hypertension is associated with cognitive decline in elderly people at high risk for dementia.
Wysocki, Michael; Luo, Xiaodong; Schmeidler, James; Dahlman, Karen; Lesser, Gerson T; Grossman, Hillel; Haroutunian, Vahram; Beeri, Michal Schnaider
2012-02-01
Cardiovascular risk factors including hypertension (HTN) have been shown to increase the risk of Alzheimer disease. The current study investigated whether individuals with HTN are more susceptible to increased cognitive decline and whether the influence of HTN on cognitive decline varied as a function of dementia severity. A total of 224 nursing home and assisted living residents, with a mean age of 84.9 (±7.6) years, were assessed longitudinally with Mini Mental State Exams (MMSEs) and Clinical Dementia Ratings (CDR). Baseline dementia status was defined by the CDR score. As described in , MMSE scores in persons with HTN and questionable dementia (CDR = 0.5) declined significantly faster than nonhypertensive questionably demented persons. Hypertensive participants did not decline significantly faster than nonhypertensive participants in persons with intact cognition (CDR = 0) or frank dementia (CDR ≥ 1). These results suggest an increased risk of subsequent cognitive decline in hypertensive individuals who are especially vulnerable to developing dementia and raises the possibility that avoiding or controlling HTN might reduce the rate of cognitive decline in cognitively vulnerable individuals, potentially delaying their conversion to full-fledged dementia.
The role of B-vitamins in preventing and treating cognitive impairment and decline
USDA-ARS?s Scientific Manuscript database
Many epidemiologic studies have considered the question of whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease (CVD), which was extended to Alzheimer’s disease...
An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans
Dean, Andy C; Groman, Stephanie M; Morales, Angelica M; London, Edythe D
2013-01-01
Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors. Here, we address this question, evaluating evidence for a priori hypotheses pertaining to six lines of research: (a) animal studies; (b) cross-sectional human studies; (c) a twin study; (d) studies of changes in cognition with abstinence from MA; (e) studies of changes in brain structure and function with abstinence from MA; and (f) studies of the relationship between the severity of MA abuse and the extent of cognitive deficits observed. Overall the findings were mixed, with some support for a causal relationship between MA abuse and cognitive decline, and other findings suggesting that there is no relationship. The preponderance of the data, however, does support the possibility that MA abuse causes cognitive decline, of unknown duration, in at least some users of the drug. When averaged across individuals, this decline is likely to be mild in early-to-middle adulthood. However, moderator variables are likely to contribute to the presence and/or severity of cognitive decline exhibited by a given individual. PMID:22948978
Clay, Olivio J.; Edwards, Jerri D.; Ross, Lesley A.; Okonkwo, Ozioma; Wadley, Virginia G.; Roth, David L.; Ball, Karlene K.
2010-01-01
Objectives: To evaluate the relationship between sensory and cognitive decline, particularly with respect to speed of processing, memory span, and fluid intelligence. Additionally, the common cause, sensory degradation and speed of processing hypotheses were compared. Methods: Structural equation modeling was used to investigate the complex relationships among age-related decrements in these areas. Results: Cross-sectional data analyses included 842 older adult participants (M = 73 years). After accounting for age-related declines in vision and processing speed, the direct associations between age and memory span and between age and fluid intelligence were nonsignificant. Older age was associated with visual decline, which was associated with slower speed of processing, which in turn was associated with greater cognitive deficits. Discussion: The findings support both the sensory degradation and speed of processing accounts of age-related cognitive decline. Further, the findings highlight positive aspects of normal cognitive aging in that older age may not be associated with a loss of fluid intelligence if visual sensory functioning and processing speed can be maintained. PMID:19436063
Verfaillie, Sander C J; Slot, Rosalinde E R; Dicks, Ellen; Prins, Niels D; Overbeek, Jozefien M; Teunissen, Charlotte E; Scheltens, Philip; Barkhof, Frederik; van der Flier, Wiesje M; Tijms, Betty M
2018-03-30
Grey matter network disruptions in Alzheimer's disease (AD) are associated with worse cognitive impairment cross-sectionally. Our aim was to investigate whether indications of a more random network organization are associated with longitudinal decline in specific cognitive functions in individuals with subjective cognitive decline (SCD). We included 231 individuals with SCD who had annually repeated neuropsychological assessment (3 ± 1 years; n = 646 neuropsychological investigations) available from the Amsterdam Dementia Cohort (54% male, age: 63 ± 9, MMSE: 28 ± 2). Single-subject grey matter networks were extracted from baseline 3D-T1 MRI scans and we computed basic network (size, degree, connectivity density) and higher-order (path length, clustering, betweenness centrality, normalized path length [lambda] and normalized clustering [gamma]) parameters at whole brain and/or regional levels. We tested associations of network parameters with baseline and annual cognition (memory, attention, executive functioning, language composite scores, and global cognition [all domains with MMSE]) using linear mixed models, adjusted for age, sex, education, scanner and total gray matter volume. Lower network size was associated with steeper decline in language (β ± SE = 0.12 ± 0.05, p < 0.05FDR). Higher-order network parameters showed no cross-sectional associations. Lower gamma and lambda values were associated with steeper decline in global cognition (gamma: β ± SE = 0.06 ± 0.02); lambda: β ± SE = 0.06 ± 0.02), language (gamma: β ± SE = 0.11 ± 0.04; lambda: β ± SE = 0.12 ± 0.05; all p < 0.05FDR). Lower path length values in precuneus and fronto-temporo-occipital cortices were associated with a steeper decline in global cognition. A more randomly organized grey matter network was associated with a steeper decline of cognitive functioning, possibly indicating the start of cognitive impairment. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Functional network integrity presages cognitive decline in preclinical Alzheimer disease.
Buckley, Rachel F; Schultz, Aaron P; Hedden, Trey; Papp, Kathryn V; Hanseeuw, Bernard J; Marshall, Gad; Sepulcre, Jorge; Smith, Emily E; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Chhatwal, Jasmeer P
2017-07-04
To examine the utility of resting-state functional connectivity MRI (rs-fcMRI) measurements of network integrity as a predictor of future cognitive decline in preclinical Alzheimer disease (AD). A total of 237 clinically normal older adults (aged 63-90 years, Clinical Dementia Rating 0) underwent baseline β-amyloid (Aβ) imaging with Pittsburgh compound B PET and structural and rs-fcMRI. We identified 7 networks for analysis, including 4 cognitive networks (default, salience, dorsal attention, and frontoparietal control) and 3 noncognitive networks (primary visual, extrastriate visual, motor). Using linear and curvilinear mixed models, we used baseline connectivity in these networks to predict longitudinal changes in preclinical Alzheimer cognitive composite (PACC) performance, both alone and interacting with Aβ burden. Median neuropsychological follow-up was 3 years. Baseline connectivity in the default, salience, and control networks predicted longitudinal PACC decline, unlike connectivity in the dorsal attention and all noncognitive networks. Default, salience, and control network connectivity was also synergistic with Aβ burden in predicting decline, with combined higher Aβ and lower connectivity predicting the steepest curvilinear decline in PACC performance. In clinically normal older adults, lower functional connectivity predicted more rapid decline in PACC scores over time, particularly when coupled with increased Aβ burden. Among examined networks, default, salience, and control networks were the strongest predictors of rate of change in PACC scores, with the inflection point of greatest decline beyond the fourth year of follow-up. These results suggest that rs-fcMRI may be a useful predictor of early, AD-related cognitive decline in clinical research settings. © 2017 American Academy of Neurology.
Bertens, Anne Suzanne; Sabayan, Behnam; de Craen, Anton J M; Van der Mast, Roos C; Gussekloo, Jacobijn
2017-01-01
Impaired cardiac function has been related to accelerated cognitive decline in late-life. To investigate whether higher levels of high sensitivity cardiac troponin T (hs-cTnT), a sensitive marker for myocardial injury, are associated with worse cognitive function in the oldest old. In 455 participants of the population-based Leiden 85-plus Study, hs-cTnT was measured at 86 years. Cognitive function was measured annually during four years with the Mini-Mental State Examination (MMSE). Participants in the highest gender-specific tertile of hs-cTnT had a 2.0-point lower baseline MMSE score than participants in the lowest tertile (95% confidence interval (CI) (95% CI 0.73-3.3), and had a 0.58-point steeper annual decline in MMSE during follow-up (95% CI 0.06-1.1). The associations remained after adjusting for sociodemographic and cardiovascular risk factors excluding those without a history of overt cardiac disease. In a population-based sample of the oldest old, higher levels of hs-cTnT were associated with worse cognitive function and faster cognitive decline, independently from cardiovascular risk factors and a history of overt cardiac disease.
Consequences of Age-Related Cognitive Declines
Salthouse, Timothy
2013-01-01
Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223
Payne, Brennan R.; Gross, Alden L.; Hill, Patrick L.; Parisi, Jeanine M.; Rebok, George W.; Stine-Morrow, Elizabeth A. L.
2018-01-01
With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2,802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability. PMID:27685541
Payne, Brennan R; Gross, Alden L; Hill, Patrick L; Parisi, Jeanine M; Rebok, George W; Stine-Morrow, Elizabeth A L
2017-07-01
With advancing age, episodic memory performance shows marked declines along with concurrent reports of lower subjective memory beliefs. Given that normative age-related declines in episodic memory co-occur with declines in other cognitive domains, we examined the relationship between memory beliefs and multiple domains of cognitive functioning. Confirmatory bi-factor structural equation models were used to parse the shared and independent variance among factors representing episodic memory, psychomotor speed, and executive reasoning in one large cohort study (Senior Odyssey, N = 462), and replicated using another large cohort of healthy older adults (ACTIVE, N = 2802). Accounting for a general fluid cognitive functioning factor (comprised of the shared variance among measures of episodic memory, speed, and reasoning) attenuated the relationship between objective memory performance and subjective memory beliefs in both samples. Moreover, the general cognitive functioning factor was the strongest predictor of memory beliefs in both samples. These findings are consistent with the notion that dispositional memory beliefs may reflect perceptions of cognition more broadly. This may be one reason why memory beliefs have broad predictive validity for interventions that target fluid cognitive ability.
Brain Protection and Cognitive Function: Cocoa Flavonoids as Nutraceuticals.
Grassi, Davide; Ferri, Claudio; Desideri, Giovambattista
2016-01-01
Cognitive decline and dementia are major public health social problems, suggesting the specific need to provide research into risk factors for cognitive decline as priority topic. Increasing evidence supports the hypothesis that oxidative stress and neuroinflammation might play a crucial role in the pathophysiology of cognitive decline. Further, cognitive dysfunction and dementia in Alzheimer's disease as well as in vascular dementia seem to be also the consequence of cerebral blood flow decrease and deregulation, also suggesting a putative pathophysiological convergence of mechanisms between atherosclerosis and Alzheimer's disease. In keeping with this, a growing interest has been addressed to flavonoids as potential nutraceuticals with neuroprotective effects. Of interest, cocoa beans have been described as a fundamental source of anti-oxidant flavonoids with the flavan-3-ols and their derivatives being present in high concentrations. Therefore, recent studies specifically focused on the favorable effects of flavonoid-rich cocoa and chocolate on cerebrovascular risk factors and cognitive function. Aim of this review is to summarize new findings concerning the cocoa effects on cognitive function, particularly focusing on some putative mechanisms of vascular and antioxidant action involved in preventing dementia.
Kazazi, Leila; Foroughan, Mahshid; Nejati, Vahid; Shati, Mohsen
2018-04-01
Age associated cognitive decline or normal cognitive aging is related with lower levels of functioning in real life, and may interfere with maintaining independence and health related quality of life (HRQL). In this study, health related quality of life and cognitive function in community-dwelling older adults were evaluated with the aim of exploring the association between them by adjusting for potential confounders. This cross-sectional study, was implemented on 425 community-dwelling older adults aged 60 and over, between August 2016 and October 2016 in health centers of the municipality of Tehran, Iran, using Mini Mental State Examination (MMSE) to assess cognitive function and Short Form-36 scales (SF-36) to assess HRQL. The relation between HRQL and cognitive function was evaluated by Pearson's correlation coefficient, and the impact of cognitive function on HRQL adjusted for potential confounders was estimated by linear regression model. All analyses were done using SPSS, version 22.0. A positive significant correlation between cognitive function and quality of life (r=0.434; p<0.001) and its dimensions was observed. Two variables of educational level (B=2.704; 95% CI: 2.09 to 3.30; p<0.001) and depression (B=2.554; 95% CI: 2.00 to 3.10; p<0.001) were assumed as potential confounder by changing effect measure after entering the model. After adjusting for potential confounders in regression model, the association between MMSE scores and quality of life persisted (B=2.417; 95% CI: 1.86 to 2.96; p<0.001). The results indicate that cognitive function was associated with HRQL in older adults with age associated cognitive function. Two variables of educational level and depression can affect the relation between cognitive decline and HRQL.
A prospective cohort study of long-term cognitive changes in older Medicare beneficiaries.
Wolinsky, Fredric D; Bentler, Suzanne E; Hockenberry, Jason; Jones, Michael P; Weigel, Paula A; Kaskie, Brian; Wallace, Robert B
2011-09-20
Promoting cognitive health and preventing its decline are longstanding public health goals, but long-term changes in cognitive function are not well-documented. Therefore, we first examined long-term changes in cognitive function among older Medicare beneficiaries in the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD), and then we identified the risk factors associated with those changes in cognitive function. We conducted a secondary analysis of a prospective, population-based cohort using baseline (1993-1994) interview data linked to 1993-2007 Medicare claims to examine cognitive function at the final follow-up interview which occurred between 1995-1996 and 2006-2007. Besides traditional risk factors (i.e., aging, age, race, and education) and adjustment for baseline cognitive function, we considered the reason for censoring (entrance into managed care or death), and post-baseline continuity of care and major health shocks (hospital episodes). Residual change score multiple linear regression analysis was used to predict cognitive function at the final follow-up using data from telephone interviews among 3,021 to 4,251 (sample size varied by cognitive outcome) baseline community-dwelling self-respondents that were ≥ 70 years old, not in managed Medicare, and had at least one follow-up interview as self-respondents. Cognitive function was assessed using the 7-item Telephone Interview for Cognitive Status (TICS-7; general mental status), and the 10-item immediate and delayed (episodic memory) word recall tests. Mean changes in the number of correct responses on the TICS-7, and 10-item immediate and delayed word recall tests were -0.33, -0.75, and -0.78, with 43.6%, 54.9%, and 52.3% declining and 25.4%, 20.8%, and 22.9% unchanged. The main and most consistent risks for declining cognitive function were the baseline values of cognitive function (reflecting substantial regression to the mean), aging (a strong linear pattern of increased decline associated with greater aging, but with diminishing marginal returns), older age at baseline, dying before the end of the study period, lower education, and minority status. In addition to aging, age, minority status, and low education, substantial and differential risks for cognitive change were associated with sooner vs. later subsequent death that help to clarify the terminal drop hypothesis. No readily modifiable protective factors were identified.
Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M
2016-08-20
Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.
Kremen, William S; Lachman, Margie E; Pruessner, Jens C; Sliwinski, Martin; Wilson, Robert S
2012-06-01
The effects of biological and physical factors on cognitive aging are widely studied. Less is known about the role of psychosocial factors such as stress and social relationships for cognitive functioning. Speakers in Session IV of the Summit focused on possible mechanisms linking social interactions and stressful experiences to cognitive changes with aging. Elevated cortisol, repetitive thinking, negative emotions, neuroticism, chronic stress, and early life adversity were negatively associated with memory and other cognitive dimensions in later life. In contrast, supportive social relationships were found to be positively related to cognitive functioning. Some evidence was provided for multidirectional, causal relationships involving stress and negative affect as both antecedents and consequences of cognitive decline. The findings contribute to understanding the potential underlying causal processes linking psychosocial factors and cognitive aging with a developmental focus on the etiology of declines and onset of cognitive impairments. This work provides an important foundation for future research to identify modifiable factors and to design interventions to minimize cognitive declines and optimize cognitive health in adulthood.
McPhee, Grace M; Downey, Luke A; Noble, Anthony; Stough, Con
2016-10-01
As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens. Cognitive training has been shown to improve performance in some cognitive domains; including memory, processing speed, executive function and attention in older adults. These cognitive changes are thought to be related to improvements in brain connectivity and neural circuitry. Bacopa monnieri has also been shown to improve specific domains of cognition, sensitive to age associated cognitive decline (particularly processing speed and memory). These Bacopa monnieri dependent improvements may be due to the increase in specific neuro-molecular mechanisms implicated in the enhancement of neural connections in the brain (i.e. synaptogenesis). In particular, a number of animal studies have shown Bacopa monnieri consumption upregulates calcium dependent kinases in the synapse and post-synaptic cell, crucial for strengthening and growing connections between neurons. These effects have been shown to occur in areas important for cognitive processes, such as the hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that encourage synaptogenesis, while cognitive training enhances brain connectivity, Bacopa monnieri supplementation could theoretically enhance and strengthen synaptic changes acquired through cognitive training. Therefore, the current paper hypothesises that the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently, as an effective treatment to ameliorate age associated cognitive decline. Copyright © 2016 Elsevier Ltd. All rights reserved.
Effect of Aging on ERP Components of Cognitive Control
Kropotov, Juri; Ponomarev, Valery; Tereshchenko, Ekaterina P.; Müller, Andreas; Jäncke, Lutz
2016-01-01
As people age, their performance on tasks requiring cognitive control often declines. Such a decline is frequently explained as either a general or specific decline in cognitive functioning with age. In the context of hypotheses suggesting a general decline, it is often proposed that processing speed generally declines with age. A further hypothesis is that an age-related compensation mechanism is associated with a specific cognitive decline. One prominent theory is the compensation hypothesis, which proposes that deteriorated functions are compensated for by higher performing functions. In this study, we used event-related potentials (ERPs) in the context of a GO/NOGO task to examine the age-related changes observed during cognitive control in a large group of healthy subjects aged between 18 and 84 years. The main question we attempted to answer was whether we could find neurophysiological support for either a general decline in processing speed or a compensation strategy. The subjects performed a relatively demanding cued GO/NOGO task with similar omissions and reaction times across the five age groups. The ERP waves of cognitive control, such as N2, P3cue and CNV, were decomposed into latent components by means of a blind source separation method. Based on this decomposition, it was possible to more precisely delineate the different neurophysiological and psychological processes involved in cognitive control. These data support the processing speed hypothesis because the latencies of all cognitive control ERP components increased with age, by 8 ms per decade for the early components (<200 ms) and by 20 ms per decade for the late components. At the same time, the compensatory hypothesis of aging was also supported, as the amplitudes of the components localized in posterior brain areas decreased with age, while those localized in the prefrontal cortical areas increased with age in order to maintain performance on this simple task at a relatively stable level. PMID:27092074
Mayo, Ann M.; Wallhagen, Margaret; Cooper, Bruce A.; Mehta, Kala; Ross, Leslie; Miller, Bruce
2012-01-01
Objective To determine the relationship between functional status (independent activities of daily living) and judgment/problem solving and the extent to which select demographic characteristics such as dementia subtype and cognitive measures may moderate that relationship in older adult individuals with dementia. Methods The National Alzheimer’s Coordinating Center Universal Data Set was accessed for a study sample of 3,855 individuals diagnosed with dementia. Primary variables included functional status, judgment/problem solving, and cognition. Results Functional status was related to judgment/problem solving (r= 0.66; p< .0005). Functional status and cognition jointly predicted 56% of the variance in judgment/problem solving (R-squared = .56, p <.0005). As cognition decreases, the prediction of poorer judgment/problem solving by functional status became stronger. Conclusions Among individuals with a diagnosis of dementia, declining functional status as well as declining cognition should raise concerns about judgment/problem solving. PMID:22786576
Cardiorespiratory Fitness Is Associated With Cognitive Performance in Older But Not Younger Adults.
Hayes, Scott M; Forman, Daniel E; Verfaellie, Mieke
2016-05-01
Aging is associated with declines in executive function and episodic memory. Cardiorespiratory fitness (CRF) has been associated with enhanced executive function in older adults (OA), but the relationship with episodic memory remains unclear. The purpose of the study was to examine the relationship between CRF and cognition in young and OA and whether CRF mitigates age-related cognitive decline. Participants completed exercise testing to evaluate CRF (peak VO2) and neuropsychological testing to assess cognition. In OA, peak VO2 was positively related to executive function, as well as to accuracy on an experimental face-name memory task and visual episodic memory. In young adults (YA), a relationship between peak VO2 and cognition was not evident. High-fit OA performed as well as YA on executive function measures. On episodic memory measures, YA performed better than high-fit OA, who in turn performed better than low-fit OA. CRF is positively associated with executive function and episodic memory in OA and attenuates age-related cognitive decline. We provide preliminary support for the age-dependence hypothesis, which posits that cognition and CRF relationships may be most readily observed during lifetime periods of significant neurocognitive development. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.
Gross, Alden L.; Mungas, Dan M.; Crane, Paul K.; Gibbons, Laura E.; MacKay-Brandt, Anna; Manly, Jennifer J.; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G.; Jones, Richard N.
2015-01-01
Objective To examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. Method To compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: 1) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N=4,115), 2) Spanish and English Neuropsychological Assessment Scales (N=525), 3) Duke Memory, Health, and Aging study (N=578), and 4) Neurocognitive Outcomes of Depression in the Elderly (N=585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. Results For baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. Discussion In this diverse set of datasets, non-Hispanic whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. PMID:26523693
Gross, Alden L; Mungas, Dan M; Crane, Paul K; Gibbons, Laura E; MacKay-Brandt, Anna; Manly, Jennifer J; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G; Jones, Richard N
2015-12-01
The objective of the study was to examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. We compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: (a) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N = 4,115), (b) Spanish and English Neuropsychological Assessment Scales (N = 525), (c) Duke Memory, Health, and Aging study (N = 578), and (d) Neurocognitive Outcomes of Depression in the Elderly (N = 585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. The results found that for baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. In this diverse set of datasets, non-Hispanic Whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. (c) 2015 APA, all rights reserved).
Kim, Se-A; Lee, Yu-Mi; Lee, Ho-Won; Jacobs, David R; Lee, Duk-Hee
2015-01-01
Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. "Lower cognitive function" was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in prospective studies.
Murayama, H; Shinkai, S; Nishi, M; Taniguchi, Y; Amano, H; Seino, S; Yokoyama, Y; Yoshida, H; Fujiwara, Y; Ito, H
2017-01-01
Cognitive function can substantially decline over a long period, and understanding the trajectory of cognitive function is important. However, little is known about the linkage between nutritional biomarkers and long-term cognitive change. We analyzed 13-year longitudinal data for older Japanese to examine the associations of serum albumin and hemoglobin levels with the trajectory of cognitive function. Longitudinal study. Community-based. A total of 1,744 community-dwelling adults aged 65 years or older who participated in annual health examinations in Kusatsu town, Gunma Prefecture, Japan, from 2002-2014. Cognitive function was assessed annually by the Mini-Mental State Examination (MMSE). Albumin and hemoglobin levels at baseline (the year when a respondent first participated in the health examination) were divided into quartiles. Hierarchical linear modeling was used to analyze intrapersonal and interpersonal differences in cognitive function. Participants' MMSE scores decreased at an accelerated rate over the 13-year period. Participants with the lowest baseline albumin level (below the first quartile line) showed a greater accelerated decline in MMSE scores over time, compared with those with the highest level (above the third quartile line). Moreover, MMSE scores in participants with a lower hemoglobin level and lower MMSE score at baseline tended to decline faster over time at an accelerated rate. These findings yield new insights about the complex and diverse roles of these nutritional biomarkers on the trajectory of cognitive function in old age.
Economic Downturns, Retirement and Long-Term Cognitive Function Among Older Americans.
Hessel, Philipp; Riumallo-Herl, Carlos J; Leist, Anja K; Berkman, Lisa F; Avendano, Mauricio
2018-04-16
Workers approaching retirement may be particularly vulnerable to economic downturns. This study assesses whether exposure to economic downturns around retirement age leads to poorer cognitive function in later life. Longitudinal data for 13,577 individuals in the Health and Retirement Study were linked to unemployment rates in state of residence. Random- and fixed-effect models were used to examine whether downturns at 55-64 years of age were associated with cognitive functioning levels and decline at ≥65 years, measured by the Wechsler Adult Intelligence Scale-Revised. Longer exposure to downturns at 55-64 years of age was associated with lower levels of cognitive function at ≥65 years. Compared to individuals experiencing only up to 1 year in a downturn at 55-64 years of age, individuals experiencing two downturns at these ages had 0.09 point (95% Confidence Interval [CI, -0.17, -0.02]) lower cognitive functioning scores at ≥65 years (3 years: b = -0.17, 95%CI [-0.29, -0.06]; 4 years: b = -0.14, 95%CI [-0.25, -0.02]; ≥5 years: b = -0.22, 95%CI [-0.38, -0.06]). Downturns at 55-64 years of age were not associated with rates of cognitive decline. Exposure to downturns around retirement is associated with a long-lasting decline in cognitive function in later life. Policies mitigating the impact of downturns on older workers may help to maintain cognitive function in later life.
Role of social support in cognitive function among elders.
Zhu, Shuzhen; Hu, Jie; Efird, Jimmy T
2012-08-01
To examine cognitive function and its relationships to demographic characteristics and social support among elders in central China. Cognitive decline is prevalent among elders. Few studies have explored the relationship between social support and cognitive function among elders. A cross-sectional, descriptive correlational study. A quasi-random, point of reference sample of 120 elders residing in central China was recruited for study. Instruments used included a: Socio-demographic Questionnaire, the Multidimensional Scale on Perceived Social Support and the Mini-Mental State Examination. Hierarchical multiple regression was performed to examine the relationships among demographic variables, social support and cognitive function. Age, education and social support accounted for 45·2% of the variance in cognitive function. Family support was the strongest predictor of cognitive function. Elders who had higher educational levels and more family support had better cognitive function. Relevance to clinical practice. Community healthcare providers should consolidate social support among elders in China and use family support interventions to reduce or delay cognitive decline, especially among those of increased age who are illiterate. Elders who had higher educational level and more family support had better cognitive function levels. Interventions that include family support are needed to improve cognitive function among elders in China. © 2012 Blackwell Publishing Ltd.
Perceived stress and change in cognitive function among adults 65 years and older.
Aggarwal, Neelum T; Wilson, Robert S; Beck, Todd L; Rajan, Kumar B; Mendes de Leon, Carlos F; Evans, Denis A; Everson-Rose, Susan A
2014-01-01
Exposure to acute and chronic stress can affect learning and memory, but most evidence comes from animal studies or clinical observations. Almost no population-based studies have investigated the relation of stress to cognition or changes in cognition over time. We examined whether higher levels of perceived stress were associated with accelerated decline in cognitive function in older blacks and whites from a community-based population sample. Participants included 6207 black and white adults (65.7% black, 63.3% women) from the Chicago Health and Aging Project. Two to five in-home assessments were completed over an average of 6.8 years of follow-up and included sociodemographics, health behaviors, psychosocial measures, cognitive function tests, and health history. Perceived stress was measured by a six-item scale, and a composite measure of four tests of cognition was used to determine cognitive function at each assessment. Mixed-effects regression models showed that increasing levels of perceived stress were related to lower initial cognitive scores (B = -0.0379, standard error = 0.0025, p < .001) and a faster rate of cognitive decline (stress × time interaction: B = -0.0015, standard error = 0.0004, p < .001). Results were similar after adjusting for demographic variables, smoking, systolic blood pressure, body mass index, chronic medical conditions, and psychosocial factors and did not vary by race, sex, age, or education. Increasing levels of stress are independently associated with accelerated declines in cognitive function in black and white adults 65 years and older.
Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.
van den Heuvel, E G H M; van Schoor, N M; Vermeer, C; Zwijsen, R M L; den Heijer, M; Comijs, H C
2015-11-01
The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D. Longitudinal study with six years follow-up. Community based. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years). Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.
Role of physical activity in reducing cognitive decline in older Mexican-American adults.
Ottenbacher, Allison J; Snih, Soham Al; Bindawas, Saad M; Markides, Kyriakos S; Graham, James E; Samper-Ternent, Rafael; Raji, Mukaila; Ottenbacher, Kenneth J
2014-09-01
The effect of physical activity on cognitive function in older adults from minority and disadvantaged populations is not well understood. This study examined the longitudinal association between physical activity and cognition in older Mexican Americans. The study methodology included a prospective cohort with longitudinal analysis of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly. General linear mixed models were used to assess the associations and interactions between physical activity and cognitive function over 14 years. Community-based assessments were performed in participants' homes. Physical activity was recorded for 1,669 older Mexican Americans using the Physical Activity Scale for the Elderly. Cognition was measured using the Mini-Mental State Examination (MMSE) and separated into memory and nonmemory components. A statistically significant positive association was observed between levels of physical activity and cognitive function after adjusting for age, sex, marital status, education, and comorbid health conditions. There was a statistically significant difference in MMSE scores over time between participants in the third (β = 0.11, standard error (SE) = 0.05) and fourth (β = 0.10, SE = 0.2) quartiles of physical activity and those in the first. The protective effect of physical activity on cognitive decline was evident for the memory component of the MMSE but not the nonmemory component after adjusting for covariates. Greater physical activity at baseline was associated with less cognitive decline over 14 years in older Mexican Americans. The reduction in cognitive decline appeared to be related to the memory components of cognitive function. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig
2015-12-01
Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.
Normal cognitive decline or dementia?
Ebmeier, Klaus P
2010-01-01
Cognitive speed, inhibitory function, and memory decline with age while crystallised, particularly verbal, abilities remain largely intact. Poor health, fewer years of education, lower activity, the presence of the APOE E4 allele, and high BP appear to predict faster cognitive decline. Dementia is diagnosed in the presence of objective cognitive impairment, both long- and short-term memory, plus at least one additional (cortical) cognitive deficit, such as dysphasia, dyspraxia, agnosia, or disturbance in executive functioning. In addition, patients have to show significant impairment in social or occupational functioning and a significant decline from previous levels. Both smoking and diabetes increase the risk of all types of dementia, not smoking or even stopping smoking reduces this risk, but better control of type 2 diabetes does not appear to have a measurable effect. Drinking small to moderate amounts of alcohol appears to confer some benefit in ameliorating cognitive decline. There is some evidence that HRT, DHEA, BP lowering in patients without prior cerebrovascular disease, statins, vitamin B6 and procaine are NOT helpful. There is insufficient evidence to establish or refute a beneficial effect for exercise, treatment of type 2 diabetes, omega-3 fatty acids, folic acid with/without vitamin B12, antioxidant vitamins, or ginkgo biloba. Depressive symptoms are more prevalent than dementia. Clinical (major) depression can present with cognitive deterioration, often associated with subjective complaints. Patients with subjective or objective memory impairment, but without functional deterioration, can be referred to the local memory clinic, while demented patients eligible for acetylcholinesterase inhibitor treatment, patients whose diagnosis is unclear and who may need some specific investigations, as well as patients who may benefit from a combined approach with psychotropic drugs and behavioural support should be referred to the local mental health team.
Qi, Xue-Mei; Gu, Lin; Tang, Hui-Dong; Chen, Sheng-Di; Ma, Jian-Fang
2018-04-20
Memory complaint is common in the elderly. Recently, it was shown that self-report memory complaint was predictive of cognitive decline. This study aimed to investigate the predictive value of the source of memory complaints on the risk of cognitive impairment and cognitive decline in a community-based cohort. Data on memory complaints and cognitive function were collected among 1840 Chinese participants (aged ≥55 years old) in an urban community at baseline interview and 5-year follow-up. Incident cognitive impairment was identified based on education-adjusted Mini-Mental State Examination score. Logistic regression model was used to estimate the association between the source of memory complaints and risk of cognitive impairment conversion and cognitive decline, after adjusting for covariates. A total of 1840 participants were included into this study including 1713 normal participants and 127 cognitive impairment participants in 2009. Among 1713 normal participants in 2009, 130 participants were converted to cognitive impairment after 5 years of follow-up. In 2014, 606 participants were identified as cognitive decline. Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.04-2.48) and cognitive decline (OR = 1.30, 95% CI: 1.01-1.68). Furthermore, this association was more significant in males (OR = 2.10, 95% CI: 1.04-4.24 for cognitive impairment and OR = 1.87, 95% CI: 1.20-2.99 for cognitive decline) and in higher education level (OR = 1.79, 95% CI: 1.02-3.15 for cognitive impairment and OR = 1.40, 95% CI: 1.02-1.91 for cognitive decline). Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment conversion and cognitive decline, especially in persons with male gender and high educational background.
Smart, Colette M; Karr, Justin E; Areshenkoff, Corson N; Rabin, Laura A; Hudon, Carol; Gates, Nicola; Ali, Jordan I; Arenaza-Urquijo, Eider M; Buckley, Rachel F; Chetelat, Gael; Hampel, Harald; Jessen, Frank; Marchant, Natalie L; Sikkes, Sietske A M; Tales, Andrea; van der Flier, Wiesje M; Wesselman, Linda
2017-09-01
In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.
Gray matter network measures are associated with cognitive decline in mild cognitive impairment.
Dicks, Ellen; Tijms, Betty M; Ten Kate, Mara; Gouw, Alida A; Benedictus, Marije R; Teunissen, Charlotte E; Barkhof, Frederik; Scheltens, Philip; van der Flier, Wiesje M
2018-01-01
Gray matter networks are disrupted in Alzheimer's disease and related to cognitive impairment. However, it is still unclear whether these disruptions are associated with cognitive decline over time. Here, we studied this question in a large sample of patients with mild cognitive impairment with extensive longitudinal neuropsychological assessments. Gray matter networks were extracted from baseline structural magnetic resonance imaging, and we tested associations of network measures and cognitive decline in Mini-Mental State Examination and 5 cognitive domains (i.e., memory, attention, executive function, visuospatial, and language). Disrupted network properties were cross-sectionally related to worse cognitive impairment. Longitudinally, lower small-world coefficient values were associated with a steeper decline in almost all domains. Lower betweenness centrality values correlated with a faster decline in Mini-Mental State Examination and memory, and at a regional level, these associations were specific for the precuneus, medial frontal, and temporal cortex. Furthermore, network measures showed additive value over established biomarkers in predicting cognitive decline. Our results suggest that gray matter network measures might have use in identifying patients who will show fast disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.
Impact of Fermented Foods on Human Cognitive Function-A Review of Outcome of Clinical Trials.
Sivamaruthi, Bhagavathi Sundaram; Kesika, Periyanaina; Chaiyasut, Chaiyavat
2018-05-31
Food is an essential need for all living creatures which provides the energy to maintain life and grow further. Fermentation is a process used to preserve and advance the quality of foods, and those foods are known as fermented foods. Some foods offer health benefits to consumers apart from nutrition, and such foods are called as functional foods. Most functional foods are fermented foods, and the fermenting microorganism plays a precious role in the functional property of the food. Cognitive decline is closely associated with the productivity of an individual and the society. Even though cognitive decline is connected to aging, dietary pattern influences memory, anxiety and other social behaviors. Many scientific studies have explained the link between food habits and cognitive functions by in vitro and in vivo models. The present review compiled the clinical data on the impact of fermented foods on human cognitive function.
Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S
2014-04-01
Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p < 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are associated with accelerated decline in global cognition and brain volumes in non-demented elderly, whereas stable IFG is not. Preventing deterioration in glucose metabolism in the elderly may help preserve brain structure and function.
Amieva, Hélène; Mokri, Hind; Le Goff, Mélanie; Meillon, Céline; Jacqmin-Gadda, Hélène; Foubert-Samier, Alexandra; Orgogozo, Jean-Marc; Stern, Yaakov; Dartigues, Jean-François
2014-04-01
A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by decline concomitantly affecting specific and more global cognitive function along with alteration in functional abilities. This study demonstrates how early cognitive symptoms may emerge preceding Alzheimer's dementia particularly in higher-educated individuals, for whom decline occurred up to 16 years before dementia. It also demonstrates the protective role of education in the clinical trajectory preceding Alzheimer's dementia. We suggest that the initial decline in cognition occurs at the onset of comparable Alzheimer's disease pathology in both groups, and is associated with immediate decline to dementia in the lower education group. In contrast, higher education protects against further cognitive decline for ∼7 years until pathology becomes more severe.
Cognitive Function Before and After Left Heart Catheterization.
Scott, David A; Evered, Lisbeth; Maruff, Paul; MacIsaac, Andrew; Maher, Sarah; Silbert, Brendan S
2018-03-10
Hospital procedures have been associated with cognitive change in older patients. This study aimed to document the prevalence of mild cognitive impairment in individuals undergoing left heart catheterization (LHC) before the procedure and the incidence of cognitive decline to 3 months afterwards. We conducted a prospective, observational, clinical investigation of elderly participants undergoing elective LHC. Cognition was assessed using a battery of written tests and a computerized cognitive battery before the LHC and then at 3 months afterwards. The computerized tests were also administered at 24 hours (or discharge) and 7 days after LHC. A control group of 51 community participants was recruited to calculate cognitive decline using the Reliable Change Index. Of 437 participants, mild cognitive impairment was identified in 226 (51.7%) before the procedure. Computerized tests detected an incidence of cognitive decline of 10.0% at 24 hours and 7.5% at 7 days. At 3 months, written tests detected an incidence of cognitive decline of 13.1% and computerized tests detected an incidence of 8.5%. Cognitive decline at 3 months using written tests was associated with increasing age, whereas computerized tests showed cognitive decline was associated with baseline amnestic mild cognitive impairment, diabetes mellitus, and prior coronary stenting. More than half the patients aged >60 years presenting for LHC have mild cognitive impairment. LHC is followed by cognitive decline in 8% to 13% of individuals at 3 months after the procedure. Subtle cognitive decline both before and after LHC is common and may have important clinical implications. URL: www.anzctr.org.au. Unique identifier: ACTRN12607000051448. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
Impaired renal function is associated with brain atrophy and poststroke cognitive decline.
Auriel, Eitan; Kliper, Efrat; Shenhar-Tsarfaty, Shani; Molad, Jeremy; Berliner, Shlomo; Shapira, Itzhak; Ben-Bashat, Dafna; Shopin, Ludmila; Tene, Oren; Rosenberg, Gary A; Bornstein, Natan M; Ben Assayag, Einor
2016-05-24
To evaluate the interrelationship among impaired renal function, brain pathology on imaging, and cognitive decline in a longitudinal poststroke cohort. The Tel Aviv Brain Acute Stroke Cohort study is a prospective cohort of mild-moderate ischemic stroke/TIA survivors without dementia who underwent a 3T MRI and were cognitively assessed at admission and for 24 months following stroke. Renal function was evaluated at admission by creatinine clearance (CCl) estimation. The volumes of ischemic lesions and preexisting white matter hyperintensities (WMH), brain atrophy, and microstructural changes of the normal-appearing white matter tissue were measured using previously validated methods. Baseline data were available for 431 participants. Participants with a CCl <60 mL/min at baseline performed significantly worse in all cognitive tests over time (p = 0.001) than those with a CCl ≥60 mL/min and had larger WMH volume and cortical atrophy and smaller hippocampal volume (all p < 0.001). After 2 years, 15.5% of the participants were diagnosed with cognitive impairment. Multiple logistic regression analysis, controlling for traditional risk factors, suggested CCl <60 mL/min at baseline as a significant predictor for the development of cognitive impairment 2 years after the index stroke (odds ratio 2.01 [95% confidence interval 1.03-3.92], p = 0.041). Impaired renal function is associated with increased WMH volume and cortical atrophy, known biomarkers of the aging brain, and is a predictor for cognitive decline 2 years after stroke/TIA. Decreased renal function may be associated with cerebral small vessel disease underlying poststroke cognitive decline, suggesting a new target for early intervention. © 2016 American Academy of Neurology.
Kok, Jeroen S; van Heuvelen, Marieke J G; Berg, Ina J; Scherder, Erik J A
2016-02-16
Evidence shows that living in small scale homelike Special Care Units (SCU) has positive effects on behavioural and psychological symptoms of patients with dementia. Effects on cognitive functioning in relation to care facilities, however, are scarcely investigated. The purpose of this study is to gain more insight into the effects of living in small scale homelike Special Care Units, compared to regular SCU's, on the course of cognitive functioning in dementia. A group of 67 patients with dementia who moved from a regular SCU to a small scale homelike SCU and a group of 48 patients with dementia who stayed in a regular SCU participated in the study. Cognitive and behavioural functioning was assessed by means of a neuropsychological test battery and observation scales one month before (baseline), as well as 3 (post) and 6 months (follow-up) after relocation. Comparing the post and follow-up measurement with the baseline measurement, no significant differences on separate measures of cognitive functioning between both groups were found. Additional analyses, however, on 'domain clusters' revealed that global cognitive functioning of the small scale homelike SCU group showed significantly less cognitive decline three months after the transfer (p < 0.05). Effect sizes (95% CI) show a tendency for better aspects of cognition in favour of the homelike small scaled SCU group, i.e., visual memory, picture recognition, cognitive decline as observed by representatives and the clustered domains episodic memory and global cognitive functioning. While there is no significant longitudinal effect on the progression of cognitive decline comparing small scaled homelike SCU's with regular SCU's for patients with dementia, analyses on the domain clusters and effect sizes cautiously suggest differences in favour of the small scaled homelike SCU for different aspects of cognition.
The Relation of Education and Income to Cognitive Function among Professional Women
Lee, Sunmin; Buring, Julie E.; Cook, Nancy R.; Grodstein, Francine
2005-01-01
We investigated the relation of educational attainment and annual household income to cognitive function and cognitive decline in community-dwelling women aged 66 years or older. Subjects were 6,314 health professionals participating in the Women’s Health Study, among whom information on education and income was self-reported. From 1998 to 2000, we administered five cognitive tests, measuring general cognition, episodic memory and verbal fluency, using a validated telephone interview. Second cognitive assessments were conducted approximately two years later; information was complete for 5,573 women at the time of analysis, with 94% follow-up. We used linear and logistic regression to calculate multivariate-adjusted mean differences, and odds of cognitive impairment (defined as worst 10% of test distribution) and of substantial decline in performance (worst 10% of distribution), across various levels of education and income. After adjusting for numerous potential confounding factors, we found strong trends of increasing mean cognitive performance with increasing level of education (p-trend<0.0005 on all cognitive measures). Odds of cognitive impairment also consistently decreased with increasing education (eg, on summary score combining all tests, OR=0.6, 95% CI 0.3–0.9 comparing those with a doctoral degree to those with a 3-year associate’s degree). For income, we found significant trends of increasing mean cognitive performance with increasing income on the summary score and on episodic memory (p-trends<0.0001). For example, the OR was 0.6 (95% CI 0.4–0.8) comparing those with the highest income to the lowest income on the summary score. Results were generally similar for cognitive decline over two years, although somewhat weaker. Thus, in these well-educated, professional women, educational attainment and income both predicted cognitive function and decline. PMID:16352912
Hollingshead, Kristy; Kaye, Jeffrey
2017-01-01
Background Alzheimer disease (AD) is a very challenging experience for all those affected. Unfortunately, detection of Alzheimer disease in its early stages when clinical treatments may be most effective is challenging, as the clinical evaluations are time-consuming and costly. Recent studies have demonstrated a close relationship between cognitive function and everyday behavior, an avenue of research that holds great promise for the early detection of cognitive decline. One area of behavior that changes with cognitive decline is language use. Multiple groups have demonstrated a close relationship between cognitive function and vocabulary size, verbal fluency, and semantic ability, using conventional in-person cognitive testing. An alternative to this approach which is inherently ecologically valid may be to take advantage of automated computer monitoring software to continually capture and analyze language use while on the computer. Objective The aim of this study was to understand the relationship between Internet searches as a measure of language and cognitive function in older adults. We hypothesize that individuals with poorer cognitive function will search using fewer unique terms, employ shorter words, and use less obscure words in their searches. Methods Computer monitoring software (WorkTime, Nestersoft Inc) was used to continuously track the terms people entered while conducting searches in Google, Yahoo, Bing, and Ask.com. For all searches, punctuation, accents, and non-ASCII characters were removed, and the resulting search terms were spell-checked before any analysis. Cognitive function was evaluated as a z-normalized summary score capturing five unique cognitive domains. Linear regression was used to determine the relationship between cognitive function and Internet searches by controlling for variables such as age, sex, and education. Results Over a 6-month monitoring period, 42 participants (mean age 81 years [SD 10.5], 83% [35/42] female) conducted 2915 searches using these top search engines. Participants averaged 3.08 words per search (SD 1.6) and 5.77 letters per word (SD 2.2). Individuals with higher cognitive function used more unique terms per search (beta=.39, P=.002) and employed less common terms in their searches (beta=1.39, P=.02). Cognitive function was not significantly associated with the length of the words used in the searches. Conclusions These results suggest that early decline in cognitive function may be detected from the terms people search for when they use the Internet. By continuously tracking basic aspects of Internet search terms, it may be possible to detect cognitive decline earlier than currently possible, thereby enabling proactive treatment and intervention. PMID:28877864
Seligman, Sarah C; Giovannetti, Tania
2015-06-01
Mild cognitive impairment (MCI) refers to the intermediate period between the typical cognitive decline of normal aging and more severe decline associated with dementia, and it is associated with greater risk for progression to dementia. Research has suggested that functional abilities are compromised in MCI, but the degree of impairment and underlying mechanisms remain poorly understood. The development of sensitive measures to assess subtle functional decline poses a major challenge for characterizing functional limitations in MCI. Eye-tracking methodology has been used to describe visual processes in everyday, naturalistic action among healthy older adults as well as several case studies of severely impaired individuals, and it has successfully differentiated healthy older adults from those with MCI on specific visual tasks. These studies highlight the promise of eye-tracking technology as a method to characterize subtle functional decline in MCI. However, to date no studies have examined visual behaviors during completion of naturalistic tasks in MCI. This review describes the current understanding of functional ability in MCI, summarizes findings of eye-tracking studies in healthy individuals, severe impairment, and MCI, and presents future research directions to aid with early identification and prevention of functional decline in disorders of aging.
Ota, Hidetaka; Akishita, Masahiro; Akiyoshi, Takuyu; Kahyo, Tomoaki; Setou, Mitsutoshi; Ogawa, Sumito; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi
2012-01-01
Oxidative stress and atherosclerosis-related vascular disorders are risk factors for cognitive decline with aging. In a small clinical study in men, testosterone improved cognitive function; however, it is unknown how testosterone ameliorates the pathogenesis of cognitive decline with aging. Here, we investigated whether the cognitive decline in senescence-accelerated mouse prone 8 (SAMP8), which exhibits cognitive impairment and hypogonadism, could be reversed by testosterone, and the mechanism by which testosterone inhibits cognitive decline. We found that treatment with testosterone ameliorated cognitive function and inhibited senescence of hippocampal vascular endothelial cells of SAMP8. Notably, SAMP8 showed enhancement of oxidative stress in the hippocampus. We observed that an NAD+-dependent deacetylase, SIRT1, played an important role in the protective effect of testosterone against oxidative stress-induced endothelial senescence. Testosterone increased eNOS activity and subsequently induced SIRT1 expression. SIRT1 inhibited endothelial senescence via up-regulation of eNOS. Finally, we showed, using co-culture system, that senescent endothelial cells promoted neuronal senescence through humoral factors. Our results suggest a critical role of testosterone and SIRT1 in the prevention of vascular and neuronal aging. PMID:22238626
Treatment effects in multiple cognitive domains in Alzheimer’s disease: a two-year cohort study
2014-01-01
Introduction Despite widespread use of second-generation cholinesterase inhibitors for the symptomatic treatment of Alzheimer’s disease (AD), little is known about the long term effects of cholinergic treatment on global cognitive function and potential specific effects in different cognitive domains. The objectives of this study were to determine the association between cholinergic treatment and global cognitive function over one and two years in a cohort of patients with mild or moderate AD and identify potential differences in domain-specific cognitive outcomes within this cohort. Methods A cohort of patients meeting the revised National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for mild or moderate AD, including patients both on treatment with a cholinesterase inhibitor and untreated controls (treated = 65, untreated = 65), were recruited from the Cognitive Neurology Clinic at Sunnybrook Health Sciences Centre, as part of the Sunnybrook Dementia Study. Patients were followed for one to two years and underwent standardized neuropsychological assessments to evaluate global and domain-specific cognitive function. Associations between cholinesterase inhibitor use and global and domain-specific cognitive outcome measures at one and two years of follow-up were estimated using mixed model linear regression, adjusting for age, education, and baseline mini mental state examination (MMSE). Results At one year, treated patients showed significantly less decline in global cognitive function, and treatment and time effects across tests of executive and visuospatial function. At two years, there was a significant trend towards less decline in global cognition for treated patients. Moreover, treated patients showed significant treatment and time effects across tests of executive functioning, memory, and visuospatial function. Conclusions The present study offers two important contributions to knowledge of the effectiveness of cholinesterase inhibitor treatment in patients with mild-moderate AD: 1) that second-generation cholinesterase inhibitors demonstrate long-term effectiveness for reducing global cognitive decline over one to two years of follow-up, and 2) that decline in function for cognitive domains, including executive function, memory, and visuospatial skill that are primarily mediated by frontal networks and by the cholinergic system, rather than memory, may be slowed by treatment targeting the cholinergic system. PMID:25484926
Can training in a real-time strategy video game attenuate cognitive decline in older adults?
Basak, Chandramallika; Boot, Walter R; Voss, Michelle W; Kramer, Arthur F
2008-12-01
Declines in various cognitive abilities, particularly executive control functions, are observed in older adults. An important goal of cognitive training is to slow or reverse these age-related declines. However, opinion is divided in the literature regarding whether cognitive training can engender transfer to a variety of cognitive skills in older adults. In the current study, the authors trained older adults in a real-time strategy video game for 23.5 hr in an effort to improve their executive functions. A battery of cognitive tasks, including tasks of executive control and visuospatial skills, were assessed before, during, and after video-game training. The trainees improved significantly in the measures of game performance. They also improved significantly more than the control participants in executive control functions, such as task switching, working memory, visual short-term memory, and reasoning. Individual differences in changes in game performance were correlated with improvements in task switching. The study has implications for the enhancement of executive control processes of older adults. Copyright (c) 2009 APA, all rights reserved.
Folic Acid Supplements: Can They Slow Cognitive Decline?
... ve heard that folic acid supplements can improve cognitive function in older adults. Could those with Alzheimer's disease also benefit ... no conclusive evidence that folic acid supplements improve cognitive function in older adults or in people with ...
Boardman, Jason D.; Barnes, Lisa L.; Wilson, Robert S.; Evans, Denis A.; Mendes de Leon, Carlos F.
2013-01-01
The goal of this paper is to describe the simultaneous influence of social and genetic risk factors on declines in cognitive functioning among older American adults. We use detailed information about the social characteristics of older adults' neighborhoods from the Chicago Health and Aging Project (n = 1655; ages 65+) in conjunction with information about respondent's APOE genotype to predict changes in cognitive function over time. Results indicate that the presence of the ɛ4 allele is associated with a significantly lower cognitive function score at baseline and greater declines in cognitive function compared to those without this risk allele. Importantly, we also show significant variation in the effect of the ɛ4 allele across neighborhoods and our results indicate that this genotype is more strongly associated with cognitive function for residents of neighborhoods with the lowest levels of social disorder. Our findings support the non-causal social push gene–environment interaction model. PMID:22465377
Dearborn, Peter J; Elias, Merrill F; Sullivan, Kevin J; Sullivan, Cara E; Robbins, Michael A
2018-06-21
Prior studies have found associations between visual acuity (VA) and cognitive function. However, these studies used a limited range of cognitive measures and did not control for cardiovascular disease risk factors (CVD-RFs) and baseline function. The primary objective of this study was to analyze the associations of VA and cognitive performance using a thorough neuropsychological test battery. This study used community-dwelling sample data across the sixth (2001-2006) and seventh (2006-2010) waves of the Maine-Syracuse Longitudinal Study (n=655). Wave 6 VA as measured by the Snellen Eye Test was the primary predictor of wave 6 and wave 7 Global cognitive performance, Visual-Spatial Organization and Memory, Verbal Episodic Memory, Working Memory, Scanning and Tracking, and Executive Function. Additionally, VA was used to predict longitudinal changes in wave 7 cognitive performance (wave 6 performance adjusted). We analyzed these relationships with multiple linear and logistic regression models adjusted for age, sex, education, ethnicity, depressive symptoms, physical function deficits in addition to CVD-RFs, chronic kidney disease, homocysteine, continuous systolic blood pressure, and hypertension status. Adjusted for demographic covariates and CVD-RFs, poorer VA was associated with concurrent and approximate 5-year declines in Global cognitive function, Visual-Spatial Organization and Memory, and Verbal Episodic Memory. VA may be used in combination with other screening measures to determine risk for cognitive decline. (JINS, 2018, 24, 1-9).
Xu, Hanzhang; Dupre, Matthew E; Gu, Danan; Wu, Bei
2017-05-15
Residential status has been linked to numerous determinants of health and well-being. However, the influence of residential status on cognitive decline remains unclear. The purpose of this research was to assess the changes of cognitive function among older adults with different residential status (urban residents, rural-to-urban residents, rural residents, and urban-to-rural residents), over a 12-year period. We used five waves of data (2002, 2005, 2008/2009, 2011/2012, and 2014) from the Chinese Longitudinal Healthy Longevity Survey with 17,333 older adults age 65 and over who were interviewed up to five times. Cognitive function was measured by the Mini Mental State Examination (MMSE). Multilevel models were used regarding the effects of residential status after adjusting for demographic characteristics, socioeconomic factors, family support, health behaviors, and health status. After controlling for covariates, significant differences in cognitive function were found across the four groups: rural-to-urban and rural residents had a higher level of cognition than urban residents at baseline. On average, cognitive function decreased over the course of the study period. Rural-to-urban and rural residents demonstrated a faster decline in cognitive function than urban residents. This study suggests that residential status has an impact on the rate of changes in cognition among older adults in China. Results from this study provide directions for future research that addresses health disparities, particularly in countries that are undergoing significant socioeconomic transitions.
HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.
Zheng, Fanfan; Yan, Li; Yang, Zhenchun; Zhong, Baoliang; Xie, Wuxiang
2018-04-01
The aim of the study was to evaluate longitudinal associations between HbA 1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period. Data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations. The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA 1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA 1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes. Significant longitudinal associations between HbA 1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.
Kovalchik, Stephanie A; Slaughter, Mary E; Miles, Jeremy; Friedman, Esther M; Shih, Regina A
2015-10-01
The influence of the sociodemographic context of one's environment on cognitive ageing is not well understood. We examined differences in cognitive trajectories according to the racial/ethnic characteristics of the residential environment. On the basis of 63 996 person-years of data from a nationally representative cohort of 6150 adults over the age of 50 years from the Health and Retirement Study, we used multivariate linear mixed models to determine the effect of neighbourhood racial/ethnic composition and county-level segregation on cognitive function and cognitive decline over a 10-year period. In models adjusting for individual demographic and health characteristics, Hispanic composition had a significant positive association with cognitive function (standardised β=0.136, p<0.05) and moderate evidence of an association with greater cognitive decline (standardised β=-0.014, p=0.09). Greater Hispanic-white segregation was associated with statistically significant higher cognitive function at baseline (standardised β=0.099, p<0.001) and greater cognitive decline (standardised β=-0.011, p<0.01). For a 20 percentage-point increase in Hispanic composition and segregation, the observed associations implied 1 and 1.25 additional years of cognitive ageing over 10 years, respectively. These effects did not differ by individual race/ethnicity and were not explained by neighbourhood socioeconomic status or neighbourhood selection. Black composition and black-white segregation did not have a significant influence on cognitive ageing. This study demonstrates disparities in the progression of cognitive ageing according to racial/ethnic characteristics of the neighbourhood environment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Bou-Orm, Ibrahim R; Khamis, Assem M; Chaaya, Monique
2018-06-01
Dementia characterized by gradual cognitive decline is an increasing public health problem due to population ageing. This study aims at assessing the prevalence and determinants of cognitive decline among Lebanese older adults. Secondary analysis of data from a cross-sectional sample of 502 elders from two Lebanese governorates was conducted. Cognitive decline was assessed using the Arabic Version of 16-item Informant Questionnaire on Cognitive Decline for the older adults (A-IQCODE 16). A multivariable logistic regression model assessed the associations of socio-demographic, clinical and behavioral factors with the presence of cognitive decline. Almost one of six Lebanese older adults (14.8%) scored below 3.34. Higher odds of cognitive decline were associated with higher age, being female, having heart disease and suffering from depression. Pack-years of cigarette smoking showed a protective effect and this relationship seems to be only statistically significant among older adults aged more than 75 years. Screening programs of cardiovascular risk factors and early detection of depression are 'best buy' public health interventions that could prevent cognitive decline among Lebanese older adults. Differential survival bias seems the reasonable explanation for the protective effect of smoking that is not the common finding from the literature.
Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.
Palta, Priya; Carlson, Michelle C; Crum, Rosa M; Colantuoni, Elizabeth; Sharrett, A Richey; Yasar, Sevil; Nahin, Richard L; DeKosky, Steven T; Snitz, Beth; Lopez, Oscar; Williamson, Jeff D; Furberg, Curt D; Rapp, Stephen R; Golden, Sherita Hill
2017-12-12
Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Rusmaully, Jennifer; Dugravot, Aline; Moatti, Jean-Paul; Marmot, Michael G; Elbaz, Alexis; Kivimaki, Mika; Sabia, Séverine; Singh-Manoux, Archana
2017-06-01
Socioeconomic disadvantage is a risk factor for dementia, but longitudinal studies suggest that it does not affect the rate of cognitive decline. Our objective is to understand the manner in which socioeconomic disadvantage shapes dementia risk by examining its associations with midlife cognitive performance and cognitive decline from midlife to old age, including cognitive decline trajectories in those with dementia. Data are drawn from the Whitehall II study (N = 10,308 at study recruitment in 1985), with cognitive function assessed at 4 waves (1997, 2002, 2007, and 2012). Sociodemographic, behavioural, and cardiometabolic risk factors from 1985 and chronic conditions until the end of follow-up in 2015 (N dementia/total = 320/9,938) allowed the use of inverse probability weighting to take into account data missing because of loss to follow-up between the study recruitment in 1985 and the introduction of cognitive tests to the study in 1997. Generalized estimating equations and Cox regression were used to assess associations of socioeconomic markers (height, education, and midlife occupation categorized as low, intermediate, and high to represent hierarchy in the socioeconomic marker) with cognitive performance, cognitive decline, and dementia (N dementia/total = 195/7,499). In those with dementia, we examined whether retrospective trajectories of cognitive decline (backward timescale) over 18 years prior to diagnosis differed as a function of socioeconomic markers. Socioeconomic disadvantage was associated with poorer cognitive performance (all p < 0.001). Using point estimates for the effect of age, the differences between the high and low socioeconomic groups corresponded to an age effect of 4, 15, and 26 years, for height, education, and midlife occupation, respectively. There was no evidence of faster cognitive decline in socioeconomically disadvantaged groups. Low occupation, but not height or education, was associated with risk of dementia (hazard ratio [HR] = 2.03 [95% confidence interval (CI) 1.23-3.36]) in an analysis adjusted for sociodemographic factors; the excess risk was unchanged after adjustment for cognitive decline but was completely attenuated after adjustment for cognitive performance. In further analyses restricted to those with dementia, retrospective cognitive trajectories over 18 years prior to dementia diagnosis showed faster cognitive decline in the high education (p = 0.006) and occupation (p = 0.001) groups such that large differences in cognitive performance in midlife were attenuated at dementia diagnosis. A major limitation of our study is the use of electronic health records rather than comprehensive dementia ascertainment. Our results support the passive or threshold cognitive reserve hypothesis, in that high cognitive reserve is associated with lower risk for dementia because of its association with cognitive performance, which provides a buffer against clinical expression of dementia.
Sink, Kaycee M.; Thomas, Joseph; Xu, Huiping; Craig, Bruce; Kritchevsky, Steven; Sands, Laura P.
2015-01-01
OBJECTIVES To determine the cognitive and functional consequences of dual use of cholinesterase inhibitors (ChIs) and the bladder anticholinergics oxybutynin or tolterodine. DESIGN Prospective cohort study. SETTING Nursing homes (NHs) in the state of Indiana. PARTICIPANTS Three thousand five hundred thirty-six Medicaid-eligible NH residents aged 65 and older taking a ChI between January 1, 2003, and December 31, 2004. Residents were excluded if they were taking an anticholinergic other than oxybutynin or tolterodine. MEASUREMENTS Indiana Medicaid claims data were merged with data from the Minimum Data Set (MDS). Repeated-measures analyses were performed to assess the effects of dual therapy on change in cognitive function measured using the MDS Cognition Scale (MDS-COGS; scored 0–10) and change in activity of daily living (ADL) function using the seven ADL items in the MDS (scored 0–28). Potential covariates included age, sex, race, number of medications, and Charlson Comorbidity Index score. RESULTS Three hundred seventy-six (10.6%) residents were prescribed oxybutynin or tolterodine concomitantly with a ChI. In residents in the top quartile of ADL function, ADL function declined an average of 1.08 points per quarter when not taking bladder anticholinergics (ChI alone), compared with 1.62 points per quarter when taking dual therapy, a 50% greater rate in quarterly decline in ADL function (P =.01). There was no excess decline attributable to dual therapy in MDS-COGS scores or in ADL function for residents who started out with lower functioning. CONCLUSION In higher-functioning NH residents, dual use of ChIs and bladder anticholinergics may result in greater rates of functional decline than use of ChIs alone. The MDS-COGS may not be sensitive enough to detect differences in cognition due to dual use. PMID:18384584
Social activity, cognitive decline and dementia risk: a 20-year prospective cohort study.
Marioni, Riccardo E; Proust-Lima, Cecile; Amieva, Helene; Brayne, Carol; Matthews, Fiona E; Dartigues, Jean-Francois; Jacqmin-Gadda, Helene
2015-10-24
Identifying modifiable lifestyle correlates of cognitive decline and risk of dementia is complex, particularly as few population-based longitudinal studies jointly model these interlinked processes. Recent methodological developments allow us to examine statistically defined sub-populations with separate cognitive trajectories and dementia risks. Engagement in social, physical, or intellectual pursuits, social network size, self-perception of feeling well understood, and degree of satisfaction with social relationships were assessed in 2854 participants from the Paquid cohort (mean baseline age 77 years) and related to incident dementia and cognitive change over 20-years of follow-up. Multivariate repeated cognitive information was exploited by defining the global cognitive functioning as the latent common factor underlying the tests. In addition, three latent homogeneous sub-populations of cognitive change and dementia were identified and contrasted according to social environment variables. In the whole population, we found associations between increased engagement in social, physical, or intellectual pursuits and increased cognitive ability (but not decline) and decreased risk of incident dementia, and between feeling understood and slower cognitive decline. There was evidence for three sub-populations of cognitive aging: fast, medium, and no cognitive decline. The social-environment measures at baseline did not help explain the heterogeneity of cognitive decline and incident dementia diagnosis between these sub-populations. We observed a complex series of relationships between social-environment variables and cognitive decline and dementia. In the whole population, factors such as increased engagement in social, physical, or intellectual pursuits were related to a decreased risk of dementia. However, in a sub-population analysis, the social-environment variables were not linked to the heterogeneous patterns of cognitive decline and dementia risk that defined the sub-groups.
Enhancing Human Cognition with Cocoa Flavonoids
Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele
2017-01-01
Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects. PMID:28560212
Enhancing Human Cognition with Cocoa Flavonoids.
Socci, Valentina; Tempesta, Daniela; Desideri, Giovambattista; De Gennaro, Luigi; Ferrara, Michele
2017-01-01
Enhancing cognitive abilities has become a fascinating scientific challenge, recently driven by the interest in preventing age-related cognitive decline and sustaining normal cognitive performance in response to cognitively demanding environments. In recent years, cocoa and cocoa-derived products, as a rich source of flavonoids, mainly the flavanols sub-class, have been clearly shown to exert cardiovascular benefits. More recently, neuromodulation and neuroprotective actions have been also suggested. Here, we discuss human studies specifically aimed at investigating the effects of acute and chronic administration of cocoa flavanols on different cognitive domains, such as executive functions, attention and memory. Through a variety of direct and indirect biological actions, in part still speculative, cocoa and cocoa-derived food have been suggested to possess the potential to counteract cognitive decline and sustain cognitive abilities, particularly among patients at risk. Although still at a preliminary stage, research investigating the relations between cocoa and cognition shows dose-dependent improvements in general cognition, attention, processing speed, and working memory. Moreover, cocoa flavanols administration could also enhance normal cognitive functioning and exert a protective role on cognitive performance and cardiovascular function specifically impaired by sleep loss, in healthy subjects. Together, these findings converge at pointing to cocoa as a new interesting nutraceutical tool to protect human cognition and counteract different types of cognitive decline, thus encouraging further investigations. Future research should include complex experimental designs combining neuroimaging techniques with physiological and behavioral measures to better elucidate cocoa neuromodulatory properties and directly compare immediate versus long-lasting cognitive effects.
ERIC Educational Resources Information Center
Anstey, Kaarin J.
2014-01-01
Optimal cognitive development is defined in this article as the highest level of cognitive function reached in each cognitive domain given a person's biological and genetic disposition, and the highest possible maintenance of cognitive function over the adult life course. Theoretical perspectives underpinning the development of a framework…
Trajectories of change in cognitive function in people with chronic obstructive pulmonary disease.
Park, Soo Kyung
2018-04-01
To describe changes in cognitive function, as measured by the trail making test; to identify distinct patterns of change in cognitive function; and to examine predictors of change in cognitive function in people with severe chronic obstructive pulmonary disease. How cognitive function changes in people with chronic obstructive pulmonary disease and what factors influence those changes over time is not well known, despite the fact that it declines rapidly in this population and significantly impacts functional decline in healthy older adults. A secondary analysis and longitudinal study with a follow-up period of 3 years. A data set from the National Emphysema Treatment Trial provided participant data. Patients with severe chronic obstructive pulmonary disease (n = 307) were recruited at a clinical site. Several demographic and clinical measures were assessed at baseline. Trail making test scores were measured at baseline, 1, 2 and 3 years. Cognitive function was stable for 3 years in people with chronic obstructive pulmonary disease. However, four distinct patterns of change in cognitive function were identified. Age, education, 6-min walk distance and cognitive impairment scores at baseline on the trail making test Part B were significant predictors of worsening cognitive function and below-average cognitive function over 3 years. These findings suggest that increasing exercise capacity improves cognitive function and delays deterioration of cognitive function in people with COPD. Understanding the trajectories of change in cognitive function and predictors of change in cognitive function over 3 years may enable health care providers to identify patients at greatest risk of developing mental deterioration and those who might benefit from interventions to improve cognitive function. Health care providers should periodically assess and frequently screen people with COPD for cognitive function. © 2018 John Wiley & Sons Ltd.
The Nature of Subjective Cognitive Complaints of Older Adults
ERIC Educational Resources Information Center
Newson, Rachel S.; Kemps, Eva B.
2006-01-01
The current study investigated the nature of subjective cognitive complaints of older adults in relation to a broad array of individual cognitive functions known to decline with age. A 60-item questionnaire was developed to examine: (1) whether older adults experience problems with these cognitive functions (problems with cognition); (2) the…
Korten, Nicole C M; Penninx, Brenda W J H; Pot, Anne Margriet; Deeg, Dorly J H; Comijs, Hannie C
2014-06-01
To examine whether persons who experienced adverse childhood events or recent negative life events have a worse cognitive performance and faster cognitive decline and the role of depression and apolipoprotein E-∊4 in this relationship. The community-based sample consisted of 10-year follow-up data of 1312 persons participating in the Longitudinal Aging Study Amsterdam (age range 65-85 years). Persons who experienced adverse childhood events showed a faster 10-year decline in processing speed but only when depressive symptoms were experienced. Persons with more recent negative life events showed slower processing speed at baseline but no faster decline. Childhood adversity may cause biological or psychological vulnerability, which is associated with both depressive symptoms and cognitive decline in later life. The accumulation of recent negative life events did not affect cognitive functioning over a longer time period. © The Author(s) 2014.
Hantke, Nathan; Nielson, Kristy A; Woodard, John L; Breting, Leslie M Guidotti; Butts, Alissa; Seidenberg, Michael; Carson Smith, J; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A; Rao, Stephen M
2013-01-01
Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively "Stable" or "Declining" based on ≥ 1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R(2) = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R(2) = .285; C index = .787), whereas the addition of EM did not (R(2) = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease.
Use it or lose it: engaged lifestyle as a buffer of cognitive decline in aging?
Hultsch, D F; Hertzog, C; Small, B J; Dixon, R A
1999-06-01
Data from the Victoria Longitudinal Study were used to examine the hypothesis that maintaining intellectual engagement through participation in everyday activities buffers individuals against cognitive decline in later life. The sample consisted of 250 middle-aged and older adults tested 3 times over 6 years. Structural equation modeling techniques were used to examine the relationships among changes in lifestyle variables and an array of cognitive variables. There was a relationship between changes in intellectually related activities and changes in cognitive functioning. These results are consistent with the hypothesis that intellectually engaging activities serve to buffer individuals against decline. However, an alternative model suggested the findings were also consistent with the hypothesis that high-ability individuals lead intellectually active lives until cognitive decline in old age limits their activities.
Functional and physical abilities in the early continuum of cognitive decline.
Shin, Joon-Ho; Lim, Jae-Young; Kim, Ki Woong; Kim, Suyoung; Lee, Jaebong; Paik, Nam-Jong
2015-01-01
The early cognitive continuum has been emphasized recently. We sought to characterize the functional and physical aspects of the cognitive continuum in subjects with no cognitive impairment (NCI), subjective cognitive impairment (SCI), nonamnestic (NA-MCI), and amnestic mild cognitive impairment (A-MCI). Furthermore, we identified the potential diagnostic utility of specific functional tasks. A total of 702 participants, aged ≥65 years and defined as NCI, SCI, NA-MCI, and A-MCI according to the original Petersen criteria, were included. They completed the Korean basic (K-ADL) and Instrumental Activities of Daily Living Scales (K-IADL) and the Performance-Oriented Mobility Assessment (POMA). Significant differences were observed between the different cognitive status groups in three items and total scores on the K-ADL, six items and total scores on the K-IADL and POMA. Controlling for confounding factors revealed that subjects from the A-MCI group performed poorly at bathing, shopping, handling money, and the sum of assorted functional items. These findings demonstrated the declining feature of functional and physical performance according to the cognitive continuum, with A-MCI being discriminative with respect to specific functional tasks as compared to milder cognitive statuses. © 2014 S. Karger AG, Basel.
[Physical activity diminishes aging-related decline of physical and cognitive performance].
Apor, Péter; Babai, László
2014-05-25
Aging-related decline of muscle force, walking speed, locomotor coordination, aerobic capacity and endurance exert prognostic impact on life expectancy. Proper use of training may diminish the aging process and it may improve the quality of life of elderly persons. This paper provides a brief summary on the impact of training on aging-related decline of physical and cognitive functions.
Differential effects of enriched environment at work on cognitive decline in old age.
Then, Francisca S; Luck, Tobias; Luppa, Melanie; König, Hans-Helmut; Angermeyer, Matthias C; Riedel-Heller, Steffi G
2015-05-26
The aim of the present study was to investigate how different mentally demanding work conditions during the professional life-i.e., enriched environments at work-might influence the rate of cognitive decline in old age. Individuals (n = 1,054) of the Leipzig Longitudinal Study of the Aged, a representative population-based cohort study of individuals aged 75 years and older, underwent cognitive testing via the Mini-Mental State Examination (MMSE) in up to 6 measurement waves. Type and level of mentally demanding work conditions in the participants' former professional life were classified based on the O*NET job descriptor database. In multivariate mixed-model analyses (controlling for sociodemographic and health-related factors), a high level of mentally demanding work tasks stimulating verbal intelligence was significantly associated with a better cognitive functioning at baseline (on average 5 MMSE points higher) as well as a lower rate of cognitive decline (on average 2 MMSE points less) over the 8-year follow-up period compared with a low level. The rate of cognitive decline in old age was also significantly lower (on average 3 MMSE points less) in individuals who had a high level of mentally demanding work tasks stimulating executive functions than those who had a low level. The results suggest that a professional life enriched with work tasks stimulating verbal intelligence and executive functions may help to sustain a good cognitive functioning in old age (75+ years). The findings thus emphasize that today's challenging work conditions may also promote positive health effects. © 2015 American Academy of Neurology.
Slavin, Melissa J; Sachdev, Perminder S; Kochan, Nicole A; Woolf, Claudia; Crawford, John D; Giskes, Katrina; Reppermund, Simone; Trollor, Julian N; Draper, Brian; Delbaere, Kim; Brodaty, Henry
2015-09-01
There is limited understanding of the usefulness of subjective cognitive complaint(s) (SCC) in predicting longitudinal outcome because most studies focus solely on memory (as opposed to nonmemory cognitive) complaints, do not collect data from both participants and informants, do not control for relevant covariates, and have limited outcome measures. Therefore the authors investigate the usefulness of participant and informant SCCs in predicting change in cognition, functional abilities, and diagnostic classification of mild cognitive impairment or dementia in a community-dwelling sample over 4 years. Nondemented participants (N = 620) in the Sydney Memory and Ageing Study aged between 70 and 90 years completed 15 memory and 9 nonmemory SCC questions. An informant completed a baseline questionnaire that included 15 memory and 4 nonmemory SCC questions relating to the participant. Neuropsychological, functional, and diagnostic assessments were carried out at baseline and again at 4-year follow-up. Cross-sectional and longitudinal analyses were carried out to determine the association between SCC indices and neuropsychological, functional, and diagnostic data while controlling for psychological measures. Once participant characteristics were controlled for, participant complaints were generally not predictive of cognitive or functional decline, although participant memory-specific complaints were predictive of diagnostic conversion. Informant-related memory questions were associated with global cognitive and functional decline and with diagnostic conversion over 4 years. Informant memory complaint questions were better than participant complaints in predicting cognitive and functional decline as well as diagnoses over 4 years. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Muniz-Terrera, Graciela; Matthews, Fiona; Dening, Tom; Huppert, Felicia A; Brayne, Carol
2009-05-01
the investigation of cognitive decline in the older population has been hampered by analytical considerations. Most studies of older people over prolonged periods suffer from loss to follow-up, yet this has seldom been investigated fully to date. Such considerations limit our understanding of how basic variables such as education can affect cognitive trajectories. we examined cognitive trajectories in a population-based cohort study in Cambridge, UK, of people aged 75 and over in whom multiple interviews were conducted over time. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Socio-demographic variables were measured, including educational level and social class. An age-based quadratic latent growth model was fitted to cognitive scores. The effect of socio-demographic variables was examined on all latent variables and the probability of death and dropout. at baseline, age, education, social class and mobility were associated with cognitive performance. Education and social class were not related to decline or its rate of change. In contrast, poor mobility was associated with lower cognitive performance, increased cognitive decline and increased rate of change of cognitive decline. Gender, age, mobility and cognitive ability predicted death and dropout contrary to much of the current literature, education was not related to rate of cognitive decline or change in this rate as measured by MMSE. Higher levels of education do not appear to protect against cognitive decline, though if the MMSE is used in the diagnostic process, individuals with less education may be diagnosed as having dementia somewhat earlier.
Hatta, Takeshi; Kato, Kimiko; Hotta, Chie; Higashikawa, Mari; Iwahara, Akihiko; Hatta, Taketoshi; Hatta, Junko; Fujiwara, Kazumi; Nagahara, Naoko; Ito, Emi; Hamajima, Nobuyuki
2017-01-01
The validity of Bucur and Madden's (2010) proposal that an age-related decline is particularly pronounced in executive function measures rather than in elementary perceptual speed measures was examined via the Yakumo Study longitudinal database. Their proposal suggests that cognitive load differentially affects cognitive abilities in older adults. To address their proposal, linear regression coefficients of 104 participants were calculated individually for the digit cancellation task 1 (D-CAT1), where participants search for a given single digit, and the D-CAT3, where they search for 3 digits simultaneously. Therefore, it can be conjectured that the D-CAT1 represents primarily elementary perceptual speed and low-visual search load task. whereas the D-CAT3 represents primarily executive function and high-visual search load task. Regression coefficients from age 65 to 75 for the D-CAT3 showed a significantly steeper decline than that for the D-CAT1, and a large number of participants showed this tendency. These results support the proposal by Brcur and Madden (2010) and suggest that the degree of cognitive load affects age-related cognitive decline.
ERIC Educational Resources Information Center
Mahoney, Rachel; Selway, Richard; Lin, Jean-Pierre
2011-01-01
Aim: To examine the cognitive functioning of young people with pantothenate-kinase-associated neurodegeneration (PKAN) after pallidal deep brain stimulation (DBS). PKAN is characterized by progressive generalized dystonia and has historically been associated with cognitive decline. With growing evidence that DBS can improve motor function in…
Bidirectional Relationship between Cognitive Function and Pneumonia
Shah, Faraaz Ali; Pike, Francis; Alvarez, Karina; Angus, Derek; Newman, Anne B.; Lopez, Oscar; Tate, Judith; Kapur, Vishesh; Wilsdon, Anthony; Krishnan, Jerry A.; Hansel, Nadia; Au, David; Avdalovic, Mark; Fan, Vincent S.; Barr, R. Graham
2013-01-01
Rationale: Relationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems. Objectives: To determine bidirectional relationships between cognition and pneumonia. Methods: We conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate. Measurements and Main Results: Of the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (β = −0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62–3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections. Conclusions: A bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence. PMID:23848267
Strategies for Preventing Cognitive Decline in Healthy Older Adults
2017-01-01
Objective: Many advances have been made in the understanding of age-related changes in cognition. As research details the cognitive and neurobiological changes that occur in aging, there is increased interest in developing and understanding methods to prevent, slow, or reverse the cognitive decline that may occur in normal healthy older adults. The Institute of Medicine has recently recognized cognitive aging as having important financial and public health implications for society with the increasing older adult population worldwide. Cognitive aging is not dementia and does not result in the loss of neurons but rather changes in neurotransmission that affect brain functioning. The fact that neurons are structurally intact but may be functionally affected by increased age implies that there is potential for remediation. Method and Results: This review article presents recent work using medication-based strategies for slowing cognitive changes in aging. The primary method presented is a hormonal approach for affecting cognition in older women. In addition, a summary of the work examining modifiable lifestyle factors that have shown promise in benefiting cognition in both older men and women is described. Conclusions: Much work remains to be done so that evidence-based recommendations can be made for slowing cognitive decline in healthy older adults. The success of some of these methods thus far indicates that the brains of healthy older adults are plastic enough to be able to respond to these cognitive decline prevention strategies, and further work is needed to define the most beneficial methods. PMID:28703016
Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease
Wang, Fen; Gordon, Brian A.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M.; Cairns, Nigel J.; Marcus, Daniel S.; McDade, Eric; Ringman, John M.; Graff-Radford, Neill R.; Ghetti, Bernardino; Farlow, Martin R.; Sperling, Reisa; Salloway, Steve; Schofield, Peter R.; Masters, Colin L.; Martins, Ralph N.; Rossor, Martin N.; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A.S.; Morris, John C.; Bateman, Randall J.
2015-01-01
Objective: To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Methods: Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89–4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. Results: In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Conclusions: Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. PMID:26245925
Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.
Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J
2015-09-01
To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.
Williamson, Jeff D; Launer, Lenore J; Bryan, R Nick; Coker, Laura H; Lazar, Ronald M; Gerstein, Hertzel C; Murray, Anne M; Sullivan, Mark D; Horowitz, Karen R; Ding, Jingzhong; Marcovina, Santica; Lovato, Laura; Lovato, James; Margolis, Karen L; Davatzikos, Christos; Barzilay, Joshua; Ginsberg, Henry N; Linz, Peter E; Miller, Michael E
2014-03-01
Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c (HbA1c) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health. Baseline mean HbA1c level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive vs standard BP-lowering group (difference, -4.4 [95% CI, -7.8 to -1.1] cm(3); P = .01). Fibrate therapy had no effect on TBV compared with placebo. In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000620.
Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Mogi, Masaki; Li Jianmei; Tsukuda, Kana
Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was notmore » affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.« less
Porges, Eric C; Woods, Adam J; Edden, Richard A E; Puts, Nicolaas A J; Harris, Ashley D; Chen, Huaihou; Garcia, Amanda M; Seider, Talia R; Lamb, Damon G; Williamson, John B; Cohen, Ronald A
2017-01-01
Gamma-aminobutyric acid (GABA), the brain's principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age. We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) 1 H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning. Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age. These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors.
Porges, Eric C.; Woods, Adam J.; Edden, Richard A.E.; Puts, Nicolaas A.J.; Harris, Ashley D.; Chen, Huaihou; Garcia, Amanda M.; Seider, Talia R.; Lamb, Damon G.; Williamson, John B.; Cohen, Ronald A.
2017-01-01
BACKGROUND Gamma-aminobutyric acid (GABA), the brain’s principal inhibitory neurotransmitter, has been associated with perceptual and attentional functioning. Recent application of magnetic resonance spectroscopy (MRS) provides in vivo evidence for decreasing GABA concentrations during adulthood. It is unclear, however, how age-related decrements in cerebral GABA concentrations contribute to cognitive decline, or whether previously reported declines in cerebral GABA concentrations persist during healthy aging. We hypothesized that participants with higher GABA concentrations in the frontal cortex would exhibit superior cognitive function and that previously reported age-related decreases in cortical GABA concentrations continue into old age. METHODS We measured GABA concentrations in frontal and posterior midline cerebral regions using a Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) 1H-MRS approach in 94 older adults without history or clinical evidence of mild cognitive impairment or dementia (mean age, 73 years). We administered the Montreal Cognitive Assessment to assess cognitive functioning. RESULTS Greater frontal GABA concentrations were associated with superior cognitive performance. This relation remained significant after controlling for age, years of education, and brain atrophy. GABA concentrations in both frontal and posterior regions decreased as a function of age. CONCLUSIONS These novel findings from a large, healthy, older population indicate that cognitive function is sensitive to cerebral GABA concentrations in the frontal cortex, and GABA concentration in frontal and posterior regions continue to decline in later age. These effects suggest that proton MRS may provide a clinically useful method for the assessment of normal and abnormal age-related cognitive changes and the associated physiological contributors. PMID:28217759
Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn
2015-01-01
Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713
Austin, Johanna; Hollingshead, Kristy; Kaye, Jeffrey
2017-09-06
Alzheimer disease (AD) is a very challenging experience for all those affected. Unfortunately, detection of Alzheimer disease in its early stages when clinical treatments may be most effective is challenging, as the clinical evaluations are time-consuming and costly. Recent studies have demonstrated a close relationship between cognitive function and everyday behavior, an avenue of research that holds great promise for the early detection of cognitive decline. One area of behavior that changes with cognitive decline is language use. Multiple groups have demonstrated a close relationship between cognitive function and vocabulary size, verbal fluency, and semantic ability, using conventional in-person cognitive testing. An alternative to this approach which is inherently ecologically valid may be to take advantage of automated computer monitoring software to continually capture and analyze language use while on the computer. The aim of this study was to understand the relationship between Internet searches as a measure of language and cognitive function in older adults. We hypothesize that individuals with poorer cognitive function will search using fewer unique terms, employ shorter words, and use less obscure words in their searches. Computer monitoring software (WorkTime, Nestersoft Inc) was used to continuously track the terms people entered while conducting searches in Google, Yahoo, Bing, and Ask.com. For all searches, punctuation, accents, and non-ASCII characters were removed, and the resulting search terms were spell-checked before any analysis. Cognitive function was evaluated as a z-normalized summary score capturing five unique cognitive domains. Linear regression was used to determine the relationship between cognitive function and Internet searches by controlling for variables such as age, sex, and education. Over a 6-month monitoring period, 42 participants (mean age 81 years [SD 10.5], 83% [35/42] female) conducted 2915 searches using these top search engines. Participants averaged 3.08 words per search (SD 1.6) and 5.77 letters per word (SD 2.2). Individuals with higher cognitive function used more unique terms per search (beta=.39, P=.002) and employed less common terms in their searches (beta=1.39, P=.02). Cognitive function was not significantly associated with the length of the words used in the searches. These results suggest that early decline in cognitive function may be detected from the terms people search for when they use the Internet. By continuously tracking basic aspects of Internet search terms, it may be possible to detect cognitive decline earlier than currently possible, thereby enabling proactive treatment and intervention. ©Johanna Austin, Kristy Hollingshead, Jeffrey Kaye. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 06.09.2017.
Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan
2015-04-01
Cognitive decline is a burdensome extra-motor symptom associated with Parkinson's disease (PD). This study aimed at investigating intrinsic functional connectivity (iFC) of the brain in cognitively unimpaired (PD-CU) and impaired PD patients (PD-CI) compared with age-matched healthy controls. "Resting-state" functional magnetic resonance imaging was acquired in 53 subjects, that is, 14 PD-CU patients, 17 PD-CI patients, and 22 control subjects. Cognition and cognitive status for patient classification were assessed using detailed neuropsychological testing. In PD-CU patients versus controls, we demonstrated significantly increased iFC (hyperconnectivity) presenting as network expansions in cortical, limbic, and basal ganglia-thalamic areas. Significantly, decreased iFC in PD-CI patients compared with control subjects was observed, predominantly between major nodes of the default mode network. In conclusion, the increased iFC might be the initial manifestation of altered brain function preceding cognitive deficits. Hyperconnectivity could be an adaptive (compensatory) mechanism by recruiting additional resources to maintain normal cognitive performance. As PD-related pathology progresses, functional disruptions within the default mode networks seem to be considerably associated with cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.
Fluid intelligence and brain functional organization in aging yoga and meditation practitioners
Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K.; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H.; Dickerson, Bradford C.; Gray, Jeremy R.; Lazar, Sara W.
2014-01-01
Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629
Pimouguet, Clément; Le-Goff, Mélanie; Rizzuto, Debora; Berr, Claudine; Leffondré, Karen; Pérès, Karine; Dartigues, Jean FranÇois; Helmer, Catherine
2016-01-01
Although early diagnosis has been hypothesized to benefit both patients and caregivers, until now studies evaluating the effect of early dementia diagnosis are lacking. To investigate the influence of early specialist referral for dementia on the risk of institutionalization and functional decline in Activity of Daily Living (ADL). Incident dementia cases were screened in a prospective population-based cohort, the Three-City Study, and initial specialist consultation for cognitive complaint was assessed at dementia diagnosis. Proportional hazard regression and illness-death models were used to test the association between specialist referral and, respectively, institutionalization and functional decline. Only one third of the incident individuals with dementia had consulted a specialist for cognitive problems early (36%). After adjustment on potential confounders (including cognitive and functional decline) and competing risk of death, participants who had consulted a specialist early in the disease course presented a higher rate of being institutionalized than those who did not (Hazard Ratio = 2.00, 95% Confidence Interval (CI): 1.09- 3.64). But early specialist referral was not associated with further functional decline (HR = 1.09, 95% CI: 0.71- 1.67). Early specialist referral in dementia is associated with increased risk of institutionalization but not with functional decline in ADL. These findings suggest that early care referral in dementia may be a marker of concern for patients and/or caregivers; subsequent medical and social care could be suboptimal or inappropriate to allow patients to stay longer at home.
Hertzog, Christopher; Kramer, Arthur F; Wilson, Robert S; Lindenberger, Ulman
2008-10-01
In this monograph, we ask whether various kinds of intellectual, physical, and social activities produce cognitive enrichment effects-that is, whether they improve cognitive performance at different points of the adult life span, with a particular emphasis on old age. We begin with a theoretical framework that emphasizes the potential of behavior to influence levels of cognitive functioning. According to this framework, the undeniable presence of age-related decline in cognition does not invalidate the view that behavior can enhance cognitive functioning. Instead, the course of normal aging shapes a zone of possible functioning, which reflects person-specific endowments and age-related constraints. Individuals influence whether they function in the higher or lower ranges of this zone by engaging in or refraining from beneficial intellectual, physical, and social activities. From this point of view, the potential for positive change, or plasticity, is maintained in adult cognition. It is an argument that is supported by newer research in neuroscience showing neural plasticity in various aspects of central nervous system functioning, neurochemistry, and architecture. This view of human potential contrasts with static conceptions of cognition in old age, according to which decline in abilities is fixed and individuals cannot slow its course. Furthermore, any understanding of cognition as it occurs in everyday life must make a distinction between basic cognitive mechanisms and skills (such as working-memory capacity) and the functional use of cognition to achieve goals in specific situations. In practice, knowledge and expertise are critical for effective functioning, and the available evidence suggests that older adults effectively employ specific knowledge and expertise and can gain new knowledge when it is required. We conclude that, on balance, the available evidence favors the hypothesis that maintaining an intellectually engaged and physically active lifestyle promotes successful cognitive aging. First, cognitive-training studies have demonstrated that older adults can improve cognitive functioning when provided with intensive training in strategies that promote thinking and remembering. The early training literature suggested little transfer of function from specifically trained skills to new cognitive tasks; learning was highly specific to the cognitive processes targeted by training. Recently, however, a new generation of studies suggests that providing structured experience in situations demanding executive coordination of skills-such as complex video games, task-switching paradigms, and divided attention tasks-train strategic control over cognition that does show transfer to different task environments. These studies suggest that there is considerable reserve potential in older adults' cognition that can be enhanced through training. Second, a considerable number of studies indicate that maintaining a lifestyle that is intellectually stimulating predicts better maintenance of cognitive skills and is associated with a reduced risk of developing Alzheimer's disease in late life. Our review focuses on longitudinal evidence of a connection between an active lifestyle and enhanced cognition, because such evidence admits fewer rival explanations of observed effects (or lack of effects) than does cross-sectional evidence. The longitudinal evidence consistently shows that engaging in intellectually stimulating activities is associated with better cognitive functioning at later points in time. Other studies show that meaningful social engagement is also predictive of better maintenance of cognitive functioning in old age. These longitudinal findings are also open to important rival explanations, but overall, the available evidence suggests that activities can postpone decline, attenuate decline, or provide prosthetic benefit in the face of normative cognitive decline, while at the same time indicating that late-life cognitive changes can result in curtailment of activities. Given the complexity of the dynamic reciprocal relationships between stimulating activities and cognitive function in old age, additional research will be needed to address the extent to which observed effects validate a causal influence of an intellectually engaged lifestyle on cognition. Nevertheless, the hypothesis that an active lifestyle that requires cognitive effort has long-term benefits for older adults' cognition is at least consistent with the available data. Furthermore, new intervention research that involves multimodal interventions focusing on goal-directed action requiring cognition (such as reading to children) and social interaction will help to address whether an active lifestyle enhances cognitive function. Third, there is a parallel literature suggesting that physical activity, and aerobic exercise in particular, enhances older adults' cognitive function. Unlike the literature on an active lifestyle, there is already an impressive array of work with humans and animal populations showing that exercise interventions have substantial benefits for cognitive function, particularly for aspects of fluid intelligence and executive function. Recent neuroscience research on this topic indicates that exercise has substantial effects on brain morphology and function, representing a plausible brain substrate for the observed effects of aerobic exercise and other activities on cognition. Our review identifies a number of areas where additional research is needed to address critical questions. For example, there is considerable epidemiological evidence that stress and chronic psychological distress are negatively associated with changes in cognition. In contrast, less is known about how positive attributes, such as self-efficacy, a sense of control, and a sense of meaning in life, might contribute to preservation of cognitive function in old age. It is well known that certain personality characteristics such as conscientiousness predict adherence to an exercise regimen, but we do not know whether these attributes are also relevant to predicting maintenance of cognitive function or effective compensation for cognitive decline when it occurs. Likewise, more information is needed on the factors that encourage maintenance of an active lifestyle in old age in the face of elevated risk for physiological decline, mechanical wear and tear on the body, and incidence of diseases with disabling consequences, and whether efforts to maintain an active lifestyle are associated with successful aging, both in terms of cognitive function and psychological and emotional well-being. We also discuss briefly some interesting issues for society and public policy regarding cognitive-enrichment effects. For example, should efforts to enhance cognitive function be included as part of a general prevention model for enhancing health and vitality in old age? We also comment on the recent trend of business marketing interventions claimed to build brain power and prevent age-related cognitive decline, and the desirability of direct research evidence to back claims of effectiveness for specific products. © 2009 Association for Psychological Science.
VanVleet, Thomas; Voss, Michelle; Dabit, Sawsan; Mitko, Alex; DeGutis, Joseph
2018-05-03
Healthy aging is associated with a decline in multiple functional domains including perception, attention, short and long-term memory, reasoning, decision-making, as well as cognitive and motor control functions; all of which are significantly modulated by an individual's level of alertness. The control of alertness also significantly declines with age and contributes to increased lapses of attention in everyday life, ranging from minor memory slips to a lack of vigilance and increased risk of falls or motor-vehicle accidents. Several experimental behavioral therapies designed to remediate age-related cognitive decline have been developed, but differ widely in content, method and dose. Preliminary studies demonstrate that Tonic and Phasic Alertness Training (TAPAT) can improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. The purpose of the current trial (referred to as the Attention training for Learning Enhancement and Resilience Trial or ALERT) is to compare TAPAT to an active control training condition, include a larger sample of patients, and assess both cognitive and functional outcomes. We will employ a multi-site, longitudinal, blinded randomized controlled trial (RCT) design with a target sample of 120 patients with age-related cognitive decline. Patients will be asked to complete 36 training sessions remotely (30 min/day, 5 days a week, over 3 months) of either the experimental TAPAT training program or an active control computer games condition. Patients will be assessed on a battery of cognitive and functional outcomes at four time points, including: a) immediately before training, b) halfway through training, c) within forty-eight hours post completion of total training, and d) after a three-month no-contact period post completion of total training, to assess the longevity of potential training effects. The strengths of this protocol are that it tests an innovative, in-home administered treatment that targets a fundamental deficit in adults with age-related cognitive decline; employs highly sensitive computer-based assessments of cognition as well as functional abilities, and incorporates a large sample size in an RCT design. ClinicalTrials.gov identifier: NCT02416401.
Matchar, David B; Chei, Choy-Lye; Yin, Zhao-Xue; Koh, Victoria; Chakraborty, Bibhas; Shi, Xiao-Ming; Zeng, Yi
2016-10-01
Vitamin D has a neuroprotective function, potentially important for the prevention of cognitive decline. Prospective studies from Western countries support an association between lower vitamin D level and future cognitive decline in elderly people. No prospective study has examined this association in Asia. This community-based cohort study of elderly people in China follows 1,202 cognitively intact adults aged ≥60 years for a mean duration of 2 years. Plasma vitamin D level was measured at the baseline. Cognitive state of participants was assessed using the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as an MMSE score <18. Cognitive decline was defined as ≥3 points decline from baseline. Multivariable logistic regression models were used to examine the association between quartiles of vitamin D levels with cognitive decline and incidence of cognitive impairment. Participants with low vitamin D level had an increased risk of cognitive decline. Compared with the highest quartile of vitamin D levels, the multivariable odds ratios (ORs; 95% confidence interval) for cognitive decline were 2.1 (1.3-3.4) for the second highest quartile, 2.2 (1.4-3.6) for the third highest quartile, and 2.0 (1.2-3.3) for the lowest quartile. The multivariable ORs of incident cognitive impairment for the second highest, third highest, and lowest versus highest quartiles of vitamin D levels were 1.9 (0.9-4.1), 2.6 (1.2-5.6), and 3.2 (1.5-6.6), respectively. This first follow-up study of elderly people, including the oldest-old, in Asia shows that low vitamin D levels were associated with increased risk of subsequent cognitive decline and impairment. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
A randomized controlled trial of Kundalini yoga in mild cognitive impairment.
Eyre, Harris A; Siddarth, Prabha; Acevedo, Bianca; Van Dyk, Kathleen; Paholpak, Pattharee; Ercoli, Linda; St Cyr, Natalie; Yang, Hongyu; Khalsa, Dharma S; Lavretsky, Helen
2017-04-01
Global population aging will result in increasing rates of cognitive decline and dementia. Thus, effective, low-cost, and low side-effect interventions for the treatment and prevention of cognitive decline are urgently needed. Our study is the first to investigate the effects of Kundalini yoga (KY) training on mild cognitive impairment (MCI). Older participants (≥55 years of age) with MCI were randomized to either a 12-week KY intervention or memory enhancement training (MET; gold-standard, active control). Cognitive (i.e. memory and executive functioning) and mood (i.e. depression, apathy, and resilience) assessments were administered at baseline, 12 weeks and 24 weeks. At baseline, 81 participants had no significant baseline group differences in clinical or demographic characteristics. At 12 weeks and 24 weeks, both KY and MET groups showed significant improvement in memory; however, only KY showed significant improvement in executive functioning. Only the KY group showed significant improvement in depressive symptoms and resilience at week 12. KY group showed short- and long-term improvements in executive functioning as compared to MET, and broader effects on depressed mood and resilience. This observation should be confirmed in future clinical trials of yoga intervention for treatment and prevention of cognitive decline (NCT01983930).
Shakersain, Behnaz; Rizzuto, Debora; Larsson, Susanna C; Faxén-Irving, Gerd; Fratiglioni, Laura; Xu, Wei-Li
2018-02-17
Appropriate dietary pattern for preserving cognitive function in northern Europe remains unknown. We aimed to identify a Nordic dietary pattern index associated with slower cognitive decline compared to the Mediterranean-DASH Intervention for Neurodegenerative Delay, Mediterranean Diet, Dietary Approaches to Stop Hypertension, and Baltic Sea Diet indices. A total of 2223 dementia-free adults aged ≥60 were followed for 6 years. Mini-Mental State Examination was administrated at baseline and follow-ups. Dietary intake was assessed by 98-item food frequency questionnaire, and the Nordic Prudent Dietary Pattern (NPDP) was identified. Data were analysed using mixed-effects and parametric survival models and receiver operating characteristic curves with adjustment for potential confounders. Moderate (β = 0.139, 95% CI 0.077-0.201) and high adherence (β = 0.238, 95% CI 0.175-0.300) to NPDP were associated with less cognitive decline compared to other four indices. High adherence to NPDP was also associated with the lowest risk of MMSE decline to ≤24 (HR = 0.176, 95% CI 0.080-0.386) and had the greatest ability to predict such decline (area under the curve = 0.70). Moderate-to-high adherence to the NPDP may predict a better-preserved cognitive function among older adults in Nordic countries. Regional dietary habits should be considered in developing dietary guidelines for the prevention of cognitive impairment and dementia.
Brasure, Michelle; Desai, Priyanka; Davila, Heather; Nelson, Victoria A; Calvert, Collin; Jutkowitz, Eric; Butler, Mary; Fink, Howard A; Ratner, Edward; Hemmy, Laura S; McCarten, J Riley; Barclay, Terry R; Kane, Robert L
2018-01-02
The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems. To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments. Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews. Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls. Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions. Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes. Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence). Agency for Healthcare Research and Quality.
Smoking increases risk for cognitive decline among community-dwelling older Mexican Americans
Collins, Nicole; Sachs-Ericsson, Natalie; Preacher, Kristopher J.; Sheffield, Kristin M.; Markides, Kyriakos
2011-01-01
Objectives Few studies have investigated smoking and cognitive decline among older Mexican Americans. In the current study we explore the relationship between smoking status and cognitive changes over time in a large sample of community-dwelling older adults of Mexican descent. Design Latent growth curve analyses were used to examine the decreasing growth in the number of correct responses on a test of cognitive functioning with increasing age (7 years with 4 data collection points). Setting In-home interviews were obtained from participants residing in the Southwest United States. Participants Participants were community-dwelling older Mexican Americans. Measurements Cognitive functioning was assessed at each of the 4 data collection points with the Mini-Mental Status Examination. Participants’ self-reports of health functioning and smoking status were obtained at baseline. Results With the inclusion of health variables and other control variables, the effect of smoking status on cognitive functioning was significant such that the decrease in the number of correct responses over time was greater for smokers than for non-smokers. Conclusions Smoking increases risk for cognitive decline among community-dwelling older Mexican Americans. There are numerous health benefits in quitting smoking, even for older adults who have been smoking for many years. Further efforts to ensure that smoking cessation and prevention programs are targeted toward Hispanics are necessary. PMID:20104052
Fronto-Parietal Subnetworks Flexibility Compensates For Cognitive Decline Due To Mental Fatigue.
Taya, Fumihiko; Dimitriadis, Stavros I; Dragomir, Andrei; Lim, Julian; Sun, Yu; Wong, Kian Foong; Thakor, Nitish V; Bezerianos, Anastasios
2018-04-24
Fronto-parietal subnetworks were revealed to compensate for cognitive decline due to mental fatigue by community structure analysis. Here, we investigate changes in topology of subnetworks of resting-state fMRI networks due to mental fatigue induced by prolonged performance of a cognitively demanding task, and their associations with cognitive decline. As it is well established that brain networks have modular organization, community structure analyses can provide valuable information about mesoscale network organization and serve as a bridge between standard fMRI approaches and brain connectomics that quantify the topology of whole brain networks. We developed inter- and intramodule network metrics to quantify topological characteristics of subnetworks, based on our hypothesis that mental fatigue would impact on functional relationships of subnetworks. Functional networks were constructed with wavelet correlation and a data-driven thresholding scheme based on orthogonal minimum spanning trees, which allowed detection of communities with weak connections. A change from pre- to posttask runs was found for the intermodule density between the frontal and the temporal subnetworks. Seven inter- or intramodule network metrics, mostly at the frontal or the parietal subnetworks, showed significant predictive power of individual cognitive decline, while the network metrics for the whole network were less effective in the predictions. Our results suggest that the control-type fronto-parietal networks have a flexible topological architecture to compensate for declining cognitive ability due to mental fatigue. This community structure analysis provides valuable insight into connectivity dynamics under different cognitive states including mental fatigue. © 2018 Wiley Periodicals, Inc.
Van Vleet, Thomas M.; DeGutis, Joseph M.; Merzenich, Michael M.; Simpson, Gregory V.; Zomet, Ativ; Dabit, Sawsan
2016-01-01
Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both experiments 1 and 2 demonstrate that, compared to active control training, alertness training significantly enhanced performance in several validated executive function measures. In experiment 2, alertness training significantly improved skill acquisition compared to active control training in a well-characterized speed of processing task, with the largest benefits shown in the most challenging speed of processing blocks. The results of the current study suggest that targeting intrinsic alertness in cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. PMID:27372902
Anstey, Kaarin J; Sargent-Cox, Kerry; Cherbuin, Nicolas; Sachdev, Perminder S
2015-06-01
There is a lack of data from cohort studies assessing cognitive function prior to and after chemotherapy. We evaluated the effect of self-reported cancer chemotherapy on cognitive function in a cohort assessed at baseline, 4 and 8 years. Participants were from the population-based PATH Through Life Study. Of the 2,551 participants aged 60-64 at baseline without cognitive impairment, 1,949 completed wave 3 and had data on cancer and chemotherapy and cognitive function. Linear mixed models were used to analyze the data. At wave 3, participants reporting history of chemotherapy (n = 76) had lower scores on memory, processing speed, and executive function compared with those reporting cancer without chemotherapy (n = 289) and no cancer history (n = 1508). After adjustment for depression and disability, effects remained for processing speed and memory. Chemotherapy prior to the study commencement (n = 24), but not between waves 1 and 3 (n = 81), was associated with greater decline in delayed recall (β = -.21 [95% CI -0.38, -.03], p = .02) and digits backwards β = -.05 [95% CI -0.09, -.01], p = .02) over 8 years compared with those with no cancer history (n = 1562). Women reporting chemotherapy for breast cancer after wave 1 (n = 26) had slower choice reaction time (-0.81 (95% CI -1.28, -0.34), p = .001) but did not decline faster on this measure compared with those reporting no breast cancer history (n = 818). Results suggest chemotherapy prior to old age is associated with faster decline in memory in late life but that it does not affect decline in other domains of cognitive function. © The Author 2013. Published by Oxford University Press on behalf of the Gerontological Society of America. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Effects of blueberries on inflammation, motor performance and cognitive function
USDA-ARS?s Scientific Manuscript database
Motor and cognitive function decrease with age, to include deficits in balance, coordination, gait, processing speed, executive function, memory, and spatial learning. These functional declines may be caused by long term increases in and susceptibility to oxidative stress and inflammation. Research ...
Cerebroprotective effect of piracetam in patients undergoing coronary bypass burgery.
Holinski, Sebastian; Claus, Benjamin; Alaaraj, Nour; Dohmen, Pascal Maria; Kirilova, Kremena; Neumann, Konrad; Uebelhack, Ralf; Konertz, Wolfgang
2008-11-01
Reduction of cognitive function is a possible side effect after cardiac surgery using cardiopulmonary bypass. We investigated the cerebroprotective effect of piracetam on cognitive performance in patients undergoing coronary artery bypass surgery under cardiopulmonary bypass. Patients scheduled for elective, primary and isolated coronary bypass surgery were randomised either to piracetam or placebo group. The study was performed in a double blind fashion. Patients received either 12 g piracetam or placebo at the beginning of the operation. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on the third postoperative day. To assess the overall cognitive function and the degree of cognitive decline across all tests after surgery we combined the six test-scores by principal component analysis. A total number of 120 patients were enrolled into the study. Preoperative overall cognitive function were not significantly different between the groups. The postoperative combined score of the neuropsychological tests showed a deterioration of cognitive function in both groups (placebo-pre: -0.06+/-0.99 vs placebo-post: -1.38+/-1.11; p<0.0005 and piracetam-pre: 0.06+/-1.02 vs piracetam-post: -0.65+/-0.93; p<0.0005). However, the piracetam patients performed significantly better compared to the placebo patients after the operation and had a less decline of overall cognitive function (p<0.0005). Piracetam has a cerebroprotective effect in patients undergoing coronary artery bypass surgery with the use of cardiopulmonary bypass. It reduces an early postoperative substantial decline of neuropsychological abilities.
Sensory-Cognitive Interactions in Older Adults
Humes, Larry E.; Young, Levi A.
2016-01-01
Objectives To review evidence regarding sensory and cognitive interactions in older adults published since 2009, the approximate date of the most recent reviews on this topic. Design Following an electronic database search of articles published in English since 2009 on measures of hearing and cognition or vision and cognition in older adults, a total of 437 articles were identified. Screening by title and abstract for appropriateness of topic and for articles presenting original research in peer-reviewed journals reduced the final number of articles reviewed to 34. These articles were qualitatively evaluated and synthesized with the existing knowledge base. Results Additional evidence has been obtained since 2009 associating declines in vision, hearing, or both with declines in cognition among older adults. The observed sensory-cognitive associations are generally stronger when more than one sensory domain is measured and when the sensory measures involve more than simple threshold sensitivity. Conclusions Evidence continues to accumulate supporting a link between decline in sensory function and cognitive decline in older adults. PMID:27355770
Sensory-Cognitive Interactions in Older Adults.
Humes, Larry E; Young, Levi A
2016-01-01
The objective of this study was regarding sensory and cognitive interactions in older adults published since 2009, the approximate date of the most recent reviews on this topic. After an electronic database search of articles published in English since 2009 on measures of hearing and cognition or vision and cognition in older adults, a total of 437 articles were identified. Screening by title and abstract for appropriateness of topic and for articles presenting original research in peer-reviewed journals reduced the final number of articles reviewed to 34. These articles were qualitatively evaluated and synthesized with the existing knowledge base. Additional evidence has been obtained since 2009 associating declines in vision, hearing, or both with declines in cognition among older adults. The observed sensory-cognitive associations are generally stronger when more than one sensory domain is measured and when the sensory measures involve more than simple threshold sensitivity. Evidence continues to accumulate supporting a link between decline in sensory function and cognitive decline in older adults.
Late Life Leisure Activities and Risk of Cognitive Decline
2013-01-01
Background. Studies concerning the effect of different types of leisure activities on various cognitive domains are limited. This study tests the hypothesis that mental, physical, and social activities have a domain-specific protection against cognitive decline. Methods. A cohort of a geographically defined population in China was examined in 2003–2005 and followed for an average of 2.4 years. Leisure activities were assessed in 1,463 adults aged 65 years and older without cognitive or physical impairment at baseline, and their cognitive performances were tested at baseline and follow-up examinations. Results. High level of mental activity was related to less decline in global cognition (β = −.23, p < .01), language (β = −.11, p < .05), and executive function (β = −.13, p < .05) in ANCOVA models adjusting for age, gender, education, history of stroke, body mass index, Apolipoprotein E genotype, and baseline cognition. High level of physical activity was related to less decline in episodic memory (β = −.08, p < .05) and language (β = −.15, p < .01). High level of social activity was associated with less decline in global cognition (β = −.11, p < .05). Further, a dose-response pattern was observed: although participants who did not engage in any of the three activities experienced a significant global cognitive decline, those who engaged in any one of the activities maintained their cognition, and those who engaged in two or three activities improved their cognition. The same pattern was observed in men and in women. Conclusions. Leisure activities in old age may protect against cognitive decline for both women and men, and different types of activities seem to benefit different cognitive domains. PMID:22879456
de Jong, L.W.; Wang, Y.; White, L.R.; Yu, B.; van Buchem, M.A.; Launer, L.J.
2012-01-01
Striatal degeneration may contribute to cognitive impairment in older people. Here, we examine the relation of degeneration of the striatum and substructures to cognitive decline and dementia in subjects with a wide range of cognitive function. Data are from the prospective community-based Honolulu Asia Aging Study of Japanese American men born 1900–1919. Brain MRI (1.5T) was acquired on a stratified sub-sample (n=477) that included four groups defined by cognitive status relative to the scan date: subjects without dementia (n=347), subjects identified as demented 2–3 years prior to brain scanning (n=30), at the time of scanning (n=58), and 3–5 years after scanning (n=42). Volumes of the striatum, including the accumbens, putamen, and caudate nucleus were automatically estimated from T1 MR images. Global cognitive function was measured with the CASI, at four exams spanning an 8 year interval. Trajectories of cognitive decline were estimated for each quartile of striatal volume using mixed models, controlling for demographic variables, measures of cerebro-vascular damage, global brain atrophy, and hippocampal volume. Diagnosis of dementia before, during, and after brain scanning was associated with smaller volumes of n. accumbens and putamen, but not with caudate nucleus volume. Subjects in the lowest quartile of n. accumbens, both in the total sample and in the subjects not diagnosed with dementia during the study, had a significantly (p < 0.0001) steeper decline in cognitive performance compared to those in the highest quartile. In conclusion, volumes of the n. accumbens and putamen are closely associated with the occurrence of dementia and n. accumbens volume predicts cognitive decline in older people. These associations were found independent of the magnitude of other pivotal markers of cognitive decline, i.e. cerebro-vascular damage and hippocampal volume. The present study suggests a role for the ventral striatum in the development of clinical dementia. PMID:21075480
Cozac, Vitalii V.; Chaturvedi, Menorca; Hatz, Florian; Meyer, Antonia; Fuhr, Peter; Gschwandtner, Ute
2016-01-01
Objective: We investigated quantitative electroencephalography (qEEG) and clinical parameters as potential risk factors of severe cognitive decline in Parkinson’s disease. Methods: We prospectively investigated 37 patients with Parkinson’s disease at baseline and follow-up (after 3 years). Patients had no severe cognitive impairment at baseline. We used a summary score of cognitive tests as the outcome at follow-up. At baseline we assessed motor, cognitive, and psychiatric factors; qEEG variables [global relative median power (GRMP) spectra] were obtained by a fully automated processing of high-resolution EEG (256-channels). We used linear regression models with calculation of the explained variance to evaluate the relation of baseline parameters with cognitive deterioration. Results: The following baseline parameters significantly predicted severe cognitive decline: GRMP theta (4–8 Hz), cognitive task performance in executive functions and working memory. Conclusions: Combination of neurocognitive tests and qEEG improves identification of patients with higher risk of cognitive decline in PD. PMID:27965571
Takeuchi, Kenji; Izumi, Maya; Furuta, Michiko; Takeshita, Toru; Shibata, Yukie; Kageyama, Shinya; Ganaha, Seijun; Yamashita, Yoshihisa
2015-01-01
Early detection and subsequent reduction of modifiable risk factors for cognitive decline is important for extending healthy life expectancy in the currently aging society. Although a recent increase in studies on the state or number of the teeth and cognitive function, few studies have focused on the association between posterior teeth occlusion necessary to maintain chewing function and cognitive function among older adults. This study examined the association between posterior teeth occlusion and cognitive function in nursing home older residents. In this cross-sectional study, 279 residents aged ≥60 years from eight nursing homes in Aso City, Japan participated in cognitive function and dental status assessments and completed a comprehensive questionnaire survey in 2014. Cognitive function was measured using a Mini-Mental State Examination (MMSE). Posterior teeth occlusion was assessed using a total number of functional tooth units (total-FTUs), depending on the number and location of the remaining natural and artificial teeth on implant-supported, fixed, and removable prostheses. Linear regression models were used to assess univariate and multivariate associations between total-FTUs and MMSE scores. Models were sequentially adjusted for demographic characteristics, number of natural teeth, socioeconomic status, health behaviors, comorbidities, physical function, and nutritional status. Among the 200 residents included in our analysis, mean MMSE scores and total-FTUs were 11.0 ± 8.6 and 9.3 ± 4.6, respectively. Higher total-FTUs were significantly associated with higher MMSE scores after adjustment for demographics and teeth number (B = 0.48, 95% confidence interval [CI] = 0.22–0.74). The association remained significant even after adjustment for all covariates (B = 0.25, 95% CI = 0.01–0.49). The current findings demonstrated that loss of posterior teeth occlusion was independently associated with cognitive decline in nursing home older residents in Japan. Maintenance and restoration of posterior teeth occlusion may be a preventive factor against cognitive decline in aged populations. PMID:26512900
Gomar, Jesus J; Bobes-Bascaran, Maria T; Conejero-Goldberg, Concepcion; Davies, Peter; Goldberg, Terry E
2011-09-01
Biomarkers have become increasingly important in understanding neurodegenerative processes associated with Alzheimer disease. Markers include regional brain volumes, cerebrospinal fluid measures of pathological Aβ1-42 and total tau, cognitive measures, and individual risk factors. To determine the discriminative utility of different classes of biomarkers and cognitive markers by examining their ability to predict a change in diagnostic status from mild cognitive impairment to Alzheimer disease. Longitudinal study. We analyzed the Alzheimer's Disease Neuroimaging Initiative database to study patients with mild cognitive impairment who converted to Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2-year period. We determined the predictive utility of 25 variables from all classes of markers, biomarkers, and risk factors in a series of logistic regression models and effect size analyses. The Alzheimer's Disease Neuroimaging Initiative public database. Primary outcome measures were odds ratios, pseudo- R(2)s, and effect sizes. In comprehensive stepwise logistic regression models that thus included variables from all classes of markers, the following baseline variables predicted conversion within a 2-year period: 2 measures of delayed verbal memory and middle temporal lobe cortical thickness. In an effect size analysis that examined rates of decline, change scores for biomarkers were modest for 2 years, but a change in an everyday functional activities measure (Functional Assessment Questionnaire) was considerably larger. Decline in scores on the Functional Assessment Questionnaire and Trail Making Test, part B, accounted for approximately 50% of the predictive variance in conversion from mild cognitive impairment to Alzheimer disease. Cognitive markers at baseline were more robust predictors of conversion than most biomarkers. Longitudinal analyses suggested that conversion appeared to be driven less by changes in the neurobiologic trajectory of the disease than by a sharp decline in functional ability and, to a lesser extent, by declines in executive function.
Meng, Annette; Siren, Anu
2012-11-01
Ageing in general is associated with functional decline that may have an adverse effect on driving. Nevertheless, older drivers have been found to show good judgement and to self-regulate their driving, which may enable them to continue driving safely despite functional decline. The process of the self-monitoring of driving ability and the awareness of functional decline, and its association with the self-regulation of driving is, however, not fully understood. The aim of the present study was to examine the perceived changes in driving skills, the discomfort experienced in driving, and the self-regulation of driving as measured by the avoidance of certain driving situations by older drivers with different levels of self-rated cognitive problems. Eight hundred and forty Danish drivers aged 75-95 completed a structured telephone interview. The results showed that the recognition of cognitive problems was associated with an experience of improvement in higher level driving skills but also of a decline in lower level driving skills. Moreover, cognitive problems recognised by drivers were associated with discomfort in, and avoidance of, driving situations. Finally, a linear relationship between discomfort in driving and avoidance was found and this tended to be stronger for drivers recognising cognitive problems. The results indicate that older drivers who recognise problems with cognitive functions display good self-assessment of changes in their driving skills. In addition, the results suggest that driving-related discomfort is an important factor affecting the self-regulation of driving. Finally, the findings indicate that driving-related discomfort functions as an indirect self-monitoring of driving ability and may contribute to the safe driving performance of Danish older drivers. Copyright © 2012 Elsevier Ltd. All rights reserved.
Aβ-related memory decline in APOE ε4 noncarriers: Implications for Alzheimer disease.
Lim, Yen Ying; Laws, Simon M; Villemagne, Victor L; Pietrzak, Robert H; Porter, Tenielle; Ames, David; Fowler, Christopher; Rainey-Smith, Stephanie; Snyder, Peter J; Martins, Ralph N; Salvado, Olivier; Bourgeat, Pierrick; Rowe, Christopher C; Masters, Colin L; Maruff, Paul
2016-04-26
As the absence of Aβ-related memory decline in APOE ε4 noncarriers may be due to the relative brevity of previous studies, we aimed to characterize Aβ-related cognitive decline over 72 months in APOE ε4 carriers and noncarriers who were cognitively normal (CN). CN older adults (n = 423) underwent Aβ imaging and APOE genotyping. Participants completed comprehensive neuropsychological testing at baseline 18-, 36-, 54-, and 72-month assessments. Relative to Aβ- CN ε4 noncarriers, both Aβ+ CN ε4 carriers and noncarriers showed significantly increased decline in measures of memory, language, and executive function as well as higher rates of progression to a clinical classification of mild cognitive impairment. Memory decline was greater in Aβ+ CN ε4 carriers than in Aβ+ CN ε4 noncarriers. No cognitive decline was evident in Aβ- CN ε4 carriers. In CN older adults, Aβ+ is associated with memory decline in ε4 noncarriers; however, the rate of this decline is much slower than that observed in ε4 carriers. These data indicate that the processes by which ε4 carriage increases the rate of Aβ-related cognitive decline occur in the preclinical stage of Alzheimer disease. © 2016 American Academy of Neurology.
Changes in executive function after acute bouts of passive cycling in Parkinson's disease.
Ridgel, Angela L; Kim, Chul-Ho; Fickes, Emily J; Muller, Matthew D; Alberts, Jay L
2011-04-01
Individuals with Parkinson's disease (PD) often experience cognitive declines. Although pharmacologic therapies are helpful in treating motor deficits in PD, they do not appear to be effective for cognitive complications. Acute bouts of moderate aerobic exercise have been shown to improve cognitive function in healthy adults. However, individuals with PD often have difficulty with exercise. This study examined the effects of passive leg cycling on executive function in PD. Executive function was assessed with Trail-Making Test (TMT) A and B before and after passive leg cycling. Significant improvements on the TMT-B test occurred after passive leg cycling. Furthermore, the difference between times to complete the TMT-B and TMT-A significantly decreased from precycling to postcycling. Improved executive function after passive cycling may be a result of increases in cerebral blood flow. These findings suggest that passive exercise could be a concurrent therapy for cognitive decline in PD.
Charlton, R A; McIntyre, D J O; Howe, F A; Morris, R G; Markus, H S
2007-08-20
Magnetic resonance spectroscopy (MRS) has demonstrated age-related changes in brain metabolites that may underlie micro-structural brain changes, but few studies have examined their relationship with cognitive decline. We performed a cross-sectional study of brain metabolism and cognitive function in 82 healthy adults (aged 50-90) participating in the GENIE (St GEorge's Neuropsychology and Imaging in the Elderly) study. Absolute metabolite concentrations were measured by proton chemical shift imaging within voxels placed in the centrum semiovale white matter. Cognitive abilities assessed were executive function, working memory, information processing speed, long-term memory and fluid intelligence. Correlations showed that all cognitive domains declined with age. Total creatine (tCr) concentration increased with age (r=0.495, p<0.001). Regression analyses were performed for each cognitive variable, including estimated intelligence and the metabolites, with age then added as a final step. A significant relationship was observed between tCr and executive function, long-term memory, and fluid intelligence, although these relationships did not remain significant after age was added as a final step in the regression. The regression analysis also demonstrated a significant relationship between N-acetylaspartate (NAA) and executive function. As there was no age-related decline in NAA, this argues against axonal loss with age; however the relationship between NAA and executive function independent of age and estimated intelligence is consistent with white matter axonal integrity having an important role in executive function in normal individuals.
Personality Predicts Cognitive Function Over Seven Years in Older Persons
Chapman, Benjamin; Duberstein, Paul; Tindle, Hilary A; Sink, Kaycee M; Robbins, John; Tancredi, Daniel J.; Franks, Peter
2011-01-01
Objectives To determine whether Neuroticism, as well as the less-studied dimensions the Five Factor Model of personality (Extraversion, Openness to Experience, Agreeableness, and Conscientiousness) were associated with 7-year trajectories of cognitive functioning in older persons. Design Primary analysis of existing clinical trial data. Participants 602 persons of average age 79 at baseline. Measurements The NEO-Five Factor Inventory of personality, completed at baseline, and the modified Mini Mental Status Exam (3MSE) measured every 6 months for 7 years. Results Controlling for demographics, baseline morbidities including depression, health behaviors, Apolipoprotein E4 genotype, and self-rated health, higher Neuroticism was associated with worse average cognitive functioning and a steeper rate of decline over follow-up. Higher Extraversion and lower Openness were both associated with worse average cognitive functioning prospectively, while persons higher in Conscientiousness showed a slower rate of cognitive decline. Conclusions In addition to Neuroticism, other dispositional tendencies appear prognostically relevant for cognitive functioning in older persons. More work is needed to understand the mechanisms by which traits operate, as well as whether mitigation of certain dispositional tendencies can facilitate a better course of cognitive function. PMID:22735597
Cognitive functioning in psychiatric disorders following deep brain stimulation.
Bergfeld, Isidoor O; Mantione, Mariska; Hoogendoorn, Mechteld L C; Denys, Damiaan
2013-07-01
Deep brain stimulation (DBS) is routinely used as a treatment for treatment-refractory Parkinson's disease and has recently been proposed for psychiatric disorders such as Tourette syndrome (TS), obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Although cognitive deterioration has repeatedly been shown in patients with Parkinson's disease following DBS, the impact of DBS on cognitive functioning in psychiatric patients has not yet been reviewed. Reviewing the available literature on cognitive functioning following DBS in psychiatric patients. A systematic literature search in PubMed, EMBASE and Web of Science, last updated in September 2012, found 1470 papers. Abstracts were scrutinized and 26 studies examining cognitive functioning of psychiatric patients following DBS were included on basis of predetermined inclusion criteria. Twenty-six studies reported cognitive functioning of 130 psychiatric patients following DBS (37 TS patients, 56 OCD patients, 28 MDD patients, 6 patients with Alzheimer's disease, and 3 patients with other disorders). None of the studies reported substantial cognitive decline following DBS. On the contrary, 13 studies reported cognitive improvement following DBS. Preliminary results suggest that DBS in psychiatric disorders does not lead to cognitive decline. In selected cases cognitive functioning was improved following DBS. However, cognitive improvement cannot be conclusively attributed to DBS since studies are hampered by serious limitations. We discuss the outcomes in light of these limitations and offer suggestions for future work. Copyright © 2013 Elsevier Inc. All rights reserved.
Six-month outcomes of co-occurring delirium, depression, and dementia in long-term care.
McCusker, Jane; Cole, Martin G; Voyer, Philippe; Monette, Johanne; Champoux, Nathalie; Ciampi, Antonio; Vu, Minh; Belzile, Eric
2014-12-01
To describe the 6-month outcomes of co-occurring delirium (full syndrome and subsyndromal symptoms), depression, and dementia in a long-term care (LTC) population. Observational, prospective cohort study with 6-month follow-up conducted from 2005 to 2009. Seven LTC facilities in the province of Quebec, Canada. Newly admitted and long-term residents recruited consecutively from lists of residents aged 65 and older admitted for LTC, with stratification into groups with and without severe cognitive impairment. The study sample comprised 274 residents with complete data at baseline on delirium, dementia, and depression. Outcomes were 6-month mortality, functional decline (10-point decline from baseline on 100-point Barthel scale), and cognitive decline (3-point decline on 30-point Mini-Mental State Examination). Predictors included delirium (full syndrome or subsyndromal symptoms, using the Confusion Assessment Method), depression (Cornell Scale for Depression in Dementia), and dementia (chart diagnosis). The baseline prevalences of delirium, subsyndromal symptoms of delirium (SSD), depression, and dementia were 11%, 44%, 19%, and 66%, respectively. By 6 months, 10% of 274 had died, 19% of 233 had experienced functional decline, and 17% of 246 had experienced cognitive decline. An analysis using multivariable generalized linear models found the following significant interaction effects (P < .15): between depression and dementia for mortality, between delirium and depression for functional decline, and between SSD and dementia for cognitive decline. Co-occurrence of delirium, SSD, depression, and dementia in LTC residents appears to affect some 6-month outcomes. Because of limited statistical power, it was not possible to draw conclusions about the effects of the co-occurrence of some syndromes on poorer outcomes. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.
Teixeira-Leite, Homero; Manhães, Alex C.
2012-01-01
OBJECTIVES: Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil. METHODS: Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale. RESULTS: Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores. CONCLUSIONS: Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity. PMID:22892914
Teixeira-Leite, Homero; Manhães, Alex C
2012-07-01
Declines in cognition and mobility are frequently observed in the elderly, and it has been suggested that the appearance of gait disorders in older individuals may constitute a marker of cognitive decline that precedes significant findings in functional performance screening tests. This study sought to evaluate the relationship between functional capacities and gait and balance in an elderly community monitored by the Preventive and Integrated Care Unit of the Hospital Adventista Silvestre in Rio de Janeiro, RJ, Brazil. Elderly individuals (193 females and 90 males) were submitted to a broad geriatric evaluation, which included the following tests: 1) a performance-oriented mobility assessment (POMA) to evaluate gait; 2) a mini-mental state examination (MMSE); 3) the use of Katz and Lawton scales to assess functional capacity; 4) the application of the geriatric depression scale (GDS); and 5) a mini-nutritional assessment (MNA) scale. Reductions in MMSE, Katz and Lawton scores were associated with reductions in POMA scores, and we also observed that significant reductions in POMA scores were present in persons for whom the MMSE and Katz scores did not clearly indicate cognitive dysfunction. We also demonstrated that a decline in the scores obtained with the GDS and MNA scales was associated with a decline in the POMA scores. Considering that significant alterations in the POMA scores were observed prior to the identification of significant alterations in cognitive capacity using either the MMSE or the Katz systems, a prospective study seems warranted to assess the predictive capacity of POMA scores regarding the associated decline in functional capacity.
Selective attrition and intraindividual variability in response time moderate cognitive change.
Yao, Christie; Stawski, Robert S; Hultsch, David F; MacDonald, Stuart W S
2016-01-01
Selection of a developmental time metric is useful for understanding causal processes that underlie aging-related cognitive change and for the identification of potential moderators of cognitive decline. Building on research suggesting that time to attrition is a metric sensitive to non-normative influences of aging (e.g., subclinical health conditions), we examined reason for attrition and intraindividual variability (IIV) in reaction time as predictors of cognitive performance. Three hundred and four community dwelling older adults (64-92 years) completed annual assessments in a longitudinal study. IIV was calculated from baseline performance on reaction time tasks. Multilevel models were fit to examine patterns and predictors of cognitive change. We show that time to attrition was associated with cognitive decline. Greater IIV was associated with declines on executive functioning and episodic memory measures. Attrition due to personal health reasons was also associated with decreased executive functioning compared to that of individuals who remained in the study. These findings suggest that time to attrition is a useful metric for representing cognitive change, and reason for attrition and IIV are predictive of non-normative influences that may underlie instances of cognitive loss in older adults.
Selective Attrition and Intraindividual Variability in Response Time Moderate Cognitive Change
Yao, Christie; Stawski, Robert S.; Hultsch, David F.; MacDonald, Stuart W.S.
2016-01-01
Objectives Selection of a developmental time metric is useful for understanding causal processes that underlie aging-related cognitive change, and for the identification of potential moderators of cognitive decline. Building on research suggesting that time to attrition is a metric sensitive to non-normative influences of aging (e.g., subclinical health conditions), we examined reason for attrition and intraindividual variability (IIV) in reaction time as predictors of cognitive performance. Method Three-hundred and four community dwelling older adults (64-92 years) completed annual assessments in a longitudinal study. IIV was calculated from baseline performance on reaction time tasks. Multilevel models were fit to examine patterns and predictors of cognitive change. Results We show that time to attrition was associated with cognitive decline. Greater IIV was associated with declines on executive functioning and episodic memory measures. Attrition due to personal health reasons was also associated with decreased executive functioning compared to individuals who remained in study. Discussion These findings suggest that time to attrition is a useful metric for representing cognitive change, and reason for attrition and IIV are predictive of non-normative influences that may underlie instances of cognitive loss in older adults. PMID:26647008
Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz
2016-01-01
To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. © 2016 Associated Professional Sleep Societies, LLC.
The hormonal pathway to cognitive impairment in older men.
Maggio, M; Dall'Aglio, E; Lauretani, F; Cattabiani, C; Ceresini, G; Caffarra, P; Valenti, G; Volpi, R; Vignali, A; Schiavi, G; Ceda, G P
2012-01-01
In older men there is a multiple hormonal dysregulation with a relative prevalence of catabolic hormones such as thyroid hormones and cortisol and a decline in anabolic hormones such as dehydroepiandrosterone sulphate, testosterone and insulin like growth factor 1 levels. Many studies suggest that this catabolic milieu is an important predictor of frailty and mortality in older persons. There is a close relationship between frailty and cognitive impairment with studies suggesting that development of frailty is consequence of cognitive impairment and others pointing out that physical frailty is a determinant of cognitive decline. Decline in cognitive function, typically memory, is a major symptom of dementia. The "preclinical phase" of cognitive impairment occurs many years before the onset of dementia. The identification of relevant modifiable factors, including the hormonal dysregulation, may lead to therapeutic strategies for preventing the cognitive dysfunction. There are several mechanisms by which anabolic hormones play a role in neuroprotection and neuromodulation. These hormones facilitate recovery after brain injury and attenuate the neuronal loss. In contrast, elevated thyroid hormones may increase oxidative stress and apoptosis, leading to neuronal damage or death. In this mini review we will address the relationship between low levels of anabolic hormones, changes in thyroid hormones and cognitive function in older men. Then, giving the contradictory data of the literature and the multi-factorial origin of dementia, we will introduce the hypothesis of multiple hormonal derangement as a better determinant of cognitive decline in older men.
Waldstein, Shari R; Wendell, Carrington Rice; Seliger, Stephen L; Ferrucci, Luigi; Metter, E Jeffrey; Zonderman, Alan B
2010-01-01
To examine the relations between the use of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin and age-related change in multiple domains of cognitive function in community-dwelling individuals without dementia. Longitudinal, with measures obtained on one to 18 occasions over up to 45 years. General community. A volunteer sample of up to 2,300 participants from the Baltimore Longitudinal Study of Aging free of diagnosed dementia. At each visit, reported NSAID or aspirin use (yes/no) and tests of verbal and visual memory, attention, perceptuo-motor speed, confrontation naming, executive function, and mental status. Mixed-effects regression models revealed that NSAID use was associated with less prospective decline on the Blessed Information-Memory-Concentration (I-M-C) Test, a mental status test weighted for memory and concentration (P<.001), and Part B of the Trail Making Test, a test of perceptuo-motor speed and mental flexibility (P<.05). In contrast, aspirin use was related to greater prospective decline on the Blessed I-M-C Test (P<.05) and the Benton Visual Retention Test, a test of visual memory (P<.001). Consistent with studies of incident dementia, NSAID users without dementia displayed less prospective decline in cognitive function, but on only two cognitive measures. In contrast, aspirin use was associated with greater prospective cognitive decline on select measures, potentially reflecting its common use for vascular disease prophylaxis. Effect sizes were small, calling into question clinical significance, although overall public health significance may be meaningful.
Mediterranean diet and cognitive function in older age: results from the Women’s Health Study
Samieri, Cécilia; Grodstein, Francine; Rosner, Bernard A.; Kang, Jae H.; Cook, Nancy R.; Manson, JoAnn E.; Buring, Julie E.; Willett, Walter C.; Okereke, Olivia I.
2013-01-01
Background Adherence to a Mediterranean diet may help prevent cognitive decline in older age, but studies are limited. We examined the association of adherence to the Mediterranean diet with cognitive function and decline. Methods We included 6,174 participants, aged 65+ years, from the cognitive sub-study of the Women’s Health Study. Women provided dietary information in 1998 and completed a cognitive battery 5 years later, followed by two assessments at 2-year intervals. The primary outcomes were composite scores of global cognition and verbal memory. The alternate Mediterranean diet adherence 9-point-score was constructed based on intakes of: vegetables, fruits, legumes, whole grains, nuts, fish, red and processed meats, moderate alcohol, and the ratio of monounsaturated-to-saturated fats. Results After multivariable adjustment, the alternate Mediterranean diet score was not associated with trajectories of repeated cognitive scores (P-trend across quintiles=0.26 and 0.40 for global cognition and verbal memory, respectively), nor with overall global cognition and verbal memory at older ages, assessed by averaging the three cognitive measures (P-trend=0.63 and 0.44, respectively). Among alternate Mediterranean diet components, higher monounsaturated-to-saturated fats ratio was associated with more favorable cognitive trajectories (P-trend=0.03 and 0.05 for global cognition and verbal memory, respectively). Greater whole grain intake was not associated with cognitive trajectories, but was related to better average global cognition (P-trend=0.02). Conclusions In this large study of older women, we observed no association of the Mediterranean diet with cognitive decline. Relations between individual Mediterranean diet components, particularly whole grains, and cognitive function merit further study. PMID:23676264
Chen, Shu-Lin; Tu, Xin; Conwell, Yeates
2017-01-01
Objectives: To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness–cognition relationship in Chinese older adults (OAs). Method: Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness–cognition relationship. Results: Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Discussion: Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness–cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. PMID:27013536
[Cognitive and functional decline in the stage previous to the diagnosis of Alzheimers disease].
García-Sánchez, C; Estévez-González, A; Boltes, A; Otermín, P; López-Góngora, M; Gironell, A; Kulisevsky, J
2003-12-01
The decline in the phase prior to diagnosis of Alzheimers disease (AD) is not well known, although this knowledge is necessary to evaluate the efficiency of new drugs that can influence in disease course prior to diagnosis. To contribute to better knowledge of the decline prior to diagnosis, we have investigated the cognitive and functional deterioration for 2-3 years before the probable AD diagnosis was established. We compared results obtained by 17 control subjects and 27 patients at the time of diagnosis of a probable AD with results obtained 2-3 years before (interval of 27.7 4 months). We compared memory functions (logical, recognition, learning and autobiographical memory), naming, visual and visuospatial gnosis, visuoconstructive praxis, verbal fluency and the Mini-Mental State Examination (MMSE), Informant Questionnaire and Blessed's Scale scores. Performance of control subjects did not change. AD patients showed a significant decline in scores, except for verbal fluency. In order of importance, cognitive decline was more marked in scores of learning memory, visuospatial gnosis, autobiographical memory and visuoconstructive praxis. Decline prior to diagnosis of AD is characterized by an important learning memory impairment. Deterioration of visuospatial gnosis and visuoconstructive praxis is greater than deterioration of MMSE and Informant Questionnaire scores.
The relationship of bilingualism to cognitive decline: The Australian Longitudinal Study of Ageing.
Mukadam, Naaheed; Jichi, Fatima; Green, David; Livingston, Gill
2018-02-01
We wished to clarify the link between bilingualism and cognitive decline, and examine whether improved executive function due to bilingualism may be a factor in preventing cognitive decline. We used the Australian Longitudinal Study of Ageing which collected data on 2087 participants aged over 65 over 20 years. We compared baseline demographics, health, and social characteristics between bilingual and non-bilingual participants. We used linear mixed models analysis to explore the effect of bilingualism on MMSE score over time and linear regression to explore the effect of bilingualism on baseline MMSE scores, controlling for pre-specified potential confounders. Bilingual participants had lower baseline MMSE scores than the non-bilingual population (mean difference = -2.3 points; 95% confidence intervals = 1.56-2.90). This was fully explained by education and National Adult Reading Test scores (17.4; standard deviation [SD] =7.7 versus 28.1; SD = 8.2) which also partly explained baseline executive function test scores differences. Bilingual and non-bilingual participants did not differ in MMSE decline over time (-0.33 points, P = 0.31) nor on baseline tests of executive function (-0.26, P = 0.051). In this cohort, education rather than bilingualism was a predictor of MMSE score, and being bilingual did not protect from cognitive decline. We conclude that bilingualism is complex, and when it is not the result of greater educational attainment, it does not always protect from cognitive decline. Neuroprotective effects of bilingualism over time may be attributable to the precise patterns of language use but not to bilingualism per se. Copyright © 2017 John Wiley & Sons, Ltd.
The Contribution of Generative Leisure Activities to Cognitive Function among Sri Lankan Elderly
Maselko, Joanna; Sebranek, Matthew; Mun, Mirna Hodzic; Perera, Bilesha; Ahs, Jill; Østbye, Truls
2014-01-01
OBJECTIVES Although a substantive body of research has shown a protective association between leisure activities and cognitive function, consistent evidence is lacking about which specific types of activities should be promoted. The objective of this analysis was to examine the unique contribution of generative leisure activities, defined as activities motivated by “a concern for others and a need to contribute something to the next generation” (Erikson). DESIGN Cross-sectional survey. SETTING Peri-urban and rural area in southern Sri Lanka. PARTICIPANTS Community dwelling adults aged 60+ (n=252). MEASUREMENTS Main predictors were leisure activities grouped into generative, social, or solitary. Main outcome was cognitive function assessed with Montreal Cognitive Assessment (MoCA) and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). RESULTS We found that more frequent engagement in generative leisure activities was associated with higher levels of cognitive function, independent of the impact of other social and solitary leisure activities. In a fully adjusted model combining all three leisure activities, generative activities independently predicted cognitive function as measured with the MoCA (β =0.47 (0.11 to 0.83) and the IQCODE (β = -0.81 (-1.54 to -0.09)). In this combined model, solitary activities were also independently associated with slower cognitive decline with the MoCA (β =0.40 (0.16, 0.64), but not with IQCODE (β =-0.38 (-0.88, 0.12)); the association with social activities did not reach statistical significance with either measure. These associations did not differ meaningfully by gender. CONCLUSION Generative leisure activities are a promising area for the development of interventions aimed at reducing cognitive decline among the elderly. PMID:25139145
Liao, Jing; Scholes, Shaun
2017-10-01
We examined whether between-persons differences and within-person changes in levels of social support were associated with age-related cognitive decline and whether these associations varied by sex and by relationship type. Executive function and memory scores over 8 years (2002-2010) were analyzed by mixture models among 10,241 adults aged ≥50 years in the English Longitudinal Study of Ageing. Between-persons differences and within-person changes in positive social support and negative social support were independently associated with cognitive decline in different ways according to sex and relationship type. Among men, higher-than-average positive social support from a spouse/partner was associated with slower cognitive decline (for executive function, βperson-mean×time-in-study = 0.005, 95% CI: 0.001, 0.010; for memory, βperson-mean×time-in-study = 0.006, 95% CI: 0.000, 0.012); whereas high negative social support from all relationship types was associated with accelerated decline in executive function (for all relationships combined, βperson-mean×time-in-study = -0.005, 95% CI: -0.008, -0.002). For women, higher-than-average positive social support from children (β = 0.037, 95% CI: 0.010, 0.064) and friends (β = 0.115, 95% CI: 0.081, 0.150)-but not from a spouse/partner (β = -0.034, 95% CI: -0.059, -0.009) or extended family (β = -0.035, 95% CI: -0.064, -0.006)-was associated with higher executive function. Associations between social support and age-related cognitive decline vary across different relationship types for men and women. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
Liao, Jing; Scholes, Shaun
2017-01-01
Abstract We examined whether between-persons differences and within-person changes in levels of social support were associated with age-related cognitive decline and whether these associations varied by sex and by relationship type. Executive function and memory scores over 8 years (2002–2010) were analyzed by mixture models among 10,241 adults aged ≥50 years in the English Longitudinal Study of Ageing. Between-persons differences and within-person changes in positive social support and negative social support were independently associated with cognitive decline in different ways according to sex and relationship type. Among men, higher-than-average positive social support from a spouse/partner was associated with slower cognitive decline (for executive function, βperson-mean×time-in-study = 0.005, 95% CI: 0.001, 0.010; for memory, βperson-mean×time-in-study = 0.006, 95% CI: 0.000, 0.012); whereas high negative social support from all relationship types was associated with accelerated decline in executive function (for all relationships combined, βperson-mean×time-in-study = −0.005, 95% CI: −0.008, −0.002). For women, higher-than-average positive social support from children (β = 0.037, 95% CI: 0.010, 0.064) and friends (β = 0.115, 95% CI: 0.081, 0.150)—but not from a spouse/partner (β = −0.034, 95% CI: −0.059, −0.009) or extended family (β = −0.035, 95% CI: −0.064, −0.006)—was associated with higher executive function. Associations between social support and age-related cognitive decline vary across different relationship types for men and women. PMID:28520853
Cognitive function in 1736 participants in NINDS Exploratory Trials in PD Long-term Study-1.
Wills, Anne-Marie A; Elm, Jordan J; Ye, Rong; Chou, Kelvin L; Parashos, Sotirios A; Hauser, Robert A; Bodis-Wollner, Ivan; Hinson, Vanessa K; Christine, Chadwick W; Schneider, Jay S
2016-12-01
Clinical cohort studies suggest that mild cognitive impairment (MCI) is common in early Parkinson's disease (PD). The objectives of this paper were to describe cognitive function in a large clinical trial of early treated PD patients at baseline and over time using two brief cognitive screening tests. In total 1741 participants were enrolled in the NINDS Exploratory Trials in Parkinson's disease (NET-PD) Long-term Study-1 (LS-1). The Symbol Digit Modalities Test (SDMT) was collected annually. The SCales for Outcomes in PArkinson's disease-COGnition (SCOPA-COG) was collected at baseline and at year 5. The trial was stopped early based on a planned interim analysis after half the cohort completed 5 years of follow-up. The median length of follow-up was 4 years (range 3-6 years). Predictors of cognitive change were examined using cross sectional (baseline) and longitudinal multivariable linear regression. The mean (SD) change from baseline to 5 years was -1.9 (5.1) for the SCOPA-COG and -2.1 (11.1) for the SDMT. Age and baseline UPDRS motor scores were associated with a more rapid decline in SDMT scores and 5 year SCOPA-COG scores. Male gender was associated with more rapid decline in SDMT. Self-reported income was a novel predictor of baseline cognitive function, even adjusted for educational status, although not significantly associated with change over time. This large prospective cohort study demonstrated mild cognitive decline in early treated Parkinson's disease. The study identified income level as a novel predictor of cognitive function. Copyright © 2016 Elsevier Ltd. All rights reserved.
Anxiety symptoms and risk of cognitive decline in older community-dwelling men.
Kassem, Ahmed M; Ganguli, Mary; Yaffe, Kristine; Hanlon, Joseph T; Lopez, Oscar L; Wilson, John W; Cauley, Jane A
2017-07-01
Previous research regarding anxiety as a predictor of future cognitive decline in older adults is limited and inconsistent. We examined the independent relationship between anxiety symptoms and subsequent cognitive decline. We included 2,818 community-dwelling older men (mean age = 76.1, SD ±5.3 years) who were followed on an average for 3.4 years. We assessed anxiety symptoms at baseline using the Goldberg Anxiety Scale (GAS; range = 0-9). We assessed cognitive function at baseline and at two subsequent visits using the Modified Mini-Mental State Examination (3MS; global cognition) and the Trails B test (executive function). At baseline, there were 690 (24%) men with mild anxiety symptoms (GAS 1-4) and 226 (8%) men with moderate/severe symptoms (GAS 5-9). Men with anxiety symptoms were more likely to have depressed mood, poor sleep, more chronic medical conditions, and more impairment in activities of daily living compared to those with no anxiety symptoms. Compared to those with no anxiety symptoms at baseline, men with any anxiety symptoms were more likely to have substantial worsening in Trails B completion time (OR = 1.56, 95% CI 1.19, 2.05). The association was attenuated after adjusting for potential confounders, including depression and poor sleep, but remained significant (OR = 1.40, 95% CI 1.04, 1.88). In cognitively healthy older men, mild anxiety symptoms may potentially predict future decline in executive functioning. Anxiety is likely a manifestation of an underlying neurodegenerative process rather than a cause.
Wang, Wang; Xiang, Hong; Xu, Huiying; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang
2017-01-01
Numerous researches supported that microbiota can influence behavior and modulate cognitive function through “microbiota-gut-brain” axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD. PMID:28099913
Gu, Chunyan; Zhou, Wen; Wang, Wang; Xiang, Hong; Xu, Huiying; Liang, Lina; Sui, Hua; Zhan, Libin; Lu, Xiaoguang
2017-04-25
Numerous researches supported that microbiota can influence behavior and modulate cognitive function through "microbiota-gut-brain" axis. Our previous study has demonstrated that ZiBuPiYin recipe (ZBPYR) possesses excellent pharmacological effects against diabetes-associated cognitive decline. To elucidate the role of ZBPYR in regulating the balance of gut microbiota to improve psychological-stress-induced diabetes-associated cognitive decline (PSDACD), we compared blood glucose, behavioral and cognitive functions and diversity of the bacterial community among experimental groups. The Zucker diabetic fatty (ZDF) rats with PSDACD exhibited behavioral and cognitive anomalies showing as increased anxiety- and depression-like behaviors and decreased learning and memory abilities. High-throughput sequencing of the bacterial 16S rRNA gene revealed that Roseburia and Coprococcus were decreased in ZDF rats with PSDACD compared with control group. Notably, these changes were reversed by ZBPYR treatment. Our findings indicate that ZBPYR might prevent PSDACD by maintaining the compositions of gut microbiota, which could be developed as a new therapy for T2D with PSDACD.
Carr, Jason A R; Honey, Christopher R; Sinden, Marci; Phillips, Anthony G; Martzke, Jeffrey S
2003-07-01
The aim of this study was to examine neuropsychological outcome from unilateral posteroventral pallidotomy (PVP) in Parkinson disease while controlling for confounding factors such as test practice and disease progression. Participants underwent baseline and 2-month follow-up assessments of cognition, quality of life, mood, and motor functioning. The surgery group (22 patients) underwent PVP (15 left, seven right) after baseline assessment. The waitlist group (14 patients) underwent PVP after follow up. At follow up, the left PVP group exhibited a decline on verbal measures of learning, fluency, working memory, and speeded color naming. The incidence of significant decline on these measures after left PVP ranged from 50 to 86%. The right PVP group did not exhibit a significant cognitive decline, but fluency did decline in 71% of patients who underwent right PVP. Participants who underwent PVP reported better bodily pain and social functioning at follow up than participants in the waitlist group. Improved bodily pain was evident for 62% of the surgery group, and social functioning improved for 19%. Surgery did not alter reported physical functioning or mood. Dyskinesia improved after surgery, but there were no improvements in "on-state" manual dexterity or handwriting. Most patients who underwent left PVP exhibited declines in learning, fluency, working memory, and speeded color naming. Accounting for retesting effects altered the magnitude of these declines by up to one quarter of a standard deviation, but did not increase the breadth of postsurgical neuropsychological decline beyond that typically reported in the literature. It was found that PVP improved dyskinesia, bodily pain, and social functioning, but did not lead to improvement on other objective and self-reported measures of motor functioning.
Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies
Arvanitakis, Z.; Yu, L.; Boyle, P. A.; Leurgans, S. E.; Bennett, D. A.
2012-01-01
Lewy bodies are common in the ageing brain and often co-occur with Alzheimer’s disease pathology. There is little known regarding the independent role of Lewy body pathology in cognition impairment, decline and fluctuations in community-dwelling older persons. We examined the contribution of Lewy body pathology to dementia, global cognition, cognitive domains, cognitive decline and fluctuations in 872 autopsied subjects (mean age = 87.9 years) from the Rush Religious Order Study (n = 491) and Memory and Aging Project (n = 381) longitudinal community-based clinical–pathological studies. Dementia was based on a clinical evaluation; annual cognitive performance tests were used to create a measure of global cognition and five cognitive domains. Lewy body type was determined by using α-synuclein immunostained sections of substantia nigra, limbic and neocortical regions. Statistical models included multiple regression models for dementia and cognition and mixed effects models for decline. Cognitive fluctuations were estimated by comparing standard deviations of individual residuals from mean trajectories of decline in those with and without Lewy bodies. All models controlled for age, sex, education, Alzheimer’s disease pathology and infarcts. One hundred and fifty-seven subjects (18%) exhibited Lewy body pathology (76 neocortical-type, 54 limbic-type and 27 nigra-predominant). One hundred and three (66%) subjects with Lewy body pathology had a pathologic diagnosis of Alzheimer’s disease. Neocortical-type, but not nigral-predominant or limbic-type Lewy body pathology was related to an increased odds of dementia (odds ratio = 3.21; 95% confidence interval = 1.78–5.81) and lower cognition (P < 0.001) including episodic memory function (P < 0.001) proximate to death. Neocortical-type Lewy body pathology was also related to a faster decline in global cognition (P < 0.001), decline in all five specific cognitive domains (all P-values < 0.001), and to fluctuations in decline of working and semantic memory (P-values < 0.001). Limbic-type Lewy body pathology was related to lower and faster decline in visuospatial skills (P = 0.042). The relationship of Lewy body pathology to cognition and dementia was not modified by Alzheimer’s disease pathology. Neocortical-type Lewy body pathology is associated with increased odds of dementia; lower and more rapid decline in all cognitive domains including episodic memory and fluctuations in decline in semantic and working memory. Limbic-type Lewy body pathology is specifically associated with lower and more rapid decline in visuospatial skills. The effect of Lewy body pathology on cognition appears to be independent of Alzheimer’s disease pathology. PMID:23065790
Ryuno, Hirochika; Kamide, Kei; Gondo, Yasuyuki; Kabayama, Mai; Oguro, Ryosuke; Nakama, Chikako; Yokoyama, Serina; Nagasawa, Motonori; Maeda-Hirao, Satomi; Imaizumi, Yuki; Takeya, Miyuki; Yamamoto, Hiroko; Takeda, Masao; Takami, Yoichi; Itoh, Norihisa; Takeya, Yasushi; Yamamoto, Koichi; Sugimoto, Ken; Nakagawa, Takeshi; Yasumoto, Saori; Ikebe, Kazunori; Inagaki, Hiroki; Masui, Yukie; Takayama, Michiyo; Arai, Yasumichi; Ishizaki, Tatsuro; Takahashi, Ryutaro; Rakugi, Hiromi
2017-07-01
Both hypertension and diabetes in middle-aged individuals have been suggested to be predictive indicators of cognitive decline. However, the association of hypertension, diabetes and their combination with cognitive functioning is still controversial in older people. The purpose of this study was to investigate the association between cognitive decline and hypertension, diabetes, and their combination in 70-year-old people based on a 3-year longitudinal analysis. Four hundred and fifty-four people aged 70 (±1) years who participated in the Japanese longitudinal cohort study of Septuagenarians, Octogenarians and Nonagenarians Investigation with Centenarians (SONIC) were recruited randomly from a general population and were monitored for 3 years. The data, including most of the demographics, cognitive functioning measured by the Montreal Cognitive Assessment Japanese version (MoCA-J), blood pressure, blood chemistry and other medical histories, were collected at baseline and during the follow-up. The prevalence of hypertension noted in the follow-up survey was significantly higher than than noted at baseline. The mean MoCA-J score at follow-up was not significantly different from the score obtained at baseline. However, the participants with diabetes, especially combined with hypertension at baseline, had significantly lower MoCA-J scores than those without lifestyle-related diseases. The combination of hypertension and diabetes was still a significant risk factor for cognitive decline, considering the MoCA-J scores obtained during the follow-up after adjustments at baseline, relative to sex, body mass index, dyslipidemia, smoking, excessive alcohol intake, antihypertensive treatment and education level (β=-0.14; P<0.01). Our findings indicate that diabetes and the combination of hypertension and diabetes are clear risk factors for future cognitive decline in elderly individuals who are 70 years of age.
Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI Study
Semba, Richard D.; Rosano, Caterina; Kalyani, Rita R.; Bandinelli, Stefania; Chia, Chee W.; Ferrucci, Luigi
2016-01-01
Background. The hormone klotho, encoded by the gene klotho, is primarily expressed in the kidney and choroid plexus of the brain. Higher klotho concentrations and certain genetic variants of klotho have been linked to better cognition; however, it is unknown whether klotho relates prospectively to slower cognitive decline in older adults. Methods: Plasma klotho was measured in 833 participants aged 55 or older without dementia enrolled in InCHIANTI, a prospective cohort study comprising Italian adults. Cognition was measured by Mini-Mental State Examination (MMSE) and Trail-Making Tests A and B (Trails A and Trails B) at enrollment and at 3 and 6 years after enrollment. We assessed whether klotho concentrations measured at the 3-year visit related to cognition and cognitive decline. Results: Each additional natural logarithm of klotho (pg/mL) was associated with 35% lower risk of meaningful decline in MMSE, defined as decline exceeding three points (relative risk = 0.65; 95% confidence interval 0.45, 0.95; p value = .02), and 0.75-point smaller average 3-year decline (baseline to 3-year visit) in MMSE (95% confidence interval 0.02, 1.48; p value = .04). No statistically significant associations were found between klotho and declining Trails A (relative risk = 0.99; 95% confidence interval 0.75, 1.32; p value = .97) and B (relative risk = 1.02; 95% confidence interval 0.84, 1.24; p value = .82). Conclusions: Higher plasma klotho concentrations were associated with lower risk of meaningful decline and smaller average decline in MMSE. We did not observe such findings with Trails A and B, perhaps because they test executive function and motor skills, whereas MMSE measures global cognition. Future studies should investigate mechanisms through which klotho may affect domain-specific cognitive changes. PMID:26297657
Ferreira, Nicola; Owen, Adrian; Mohan, Anita; Corbett, Anne; Ballard, Clive
2015-04-01
Emerging literature suggests that lifestyle factors may play an important role in reducing age-related cognitive decline. There have, however, been few studies investigating the role of cognitively stimulating leisure activities in maintaining cognitive health. This study sought to identify changes in cognitive performance with age and to investigate associations of cognitive performance with several key cognitively stimulating leisure activities. Over 65,000 participants provided demographic and lifestyle information and completed tests of grammatical reasoning, spatial working memory, verbal working memory and episodic memory. Regression analyses suggested that frequency of engaging in Sudoku or similar puzzles was significantly positively associated with grammatical reasoning, spatial working memory and episodic memory scores. Furthermore, for participants aged under 65 years, frequency of playing non-cognitive training computer games was also positively associated with performance in the same cognitive domains. The results also suggest that grammatical reasoning and episodic memory are particularly vulnerable to age-related decline. Further investigation to determine the potential benefits of participating in Sudoku puzzles and non-cognitive computer games is indicated, particularly as they are associated with grammatical reasoning and episodic memory, cognitive domains found to be strongly associated with age-related cognitive decline. Results of this study have implications for developing improved guidance for the public regarding the potential value of cognitively stimulating leisure activities. The results also suggest that grammatical reasoning and episodic memory should be targeted in developing appropriate outcome measures to assess efficacy of future interventions, and in developing cognitive training programmes to prevent or delay cognitive decline. Copyright © 2014 John Wiley & Sons, Ltd.
Anstey, Kaarin J; Horswill, Mark S; Wood, Joanne M; Hatherly, Christopher
2012-03-01
The current study evaluated part of the Multifactorial Model of Driving Safety to elucidate the relative importance of cognitive function and a limited range of standard measures of visual function in relation to the Capacity to Drive Safely. Capacity to Drive Safely was operationalized using three validated screening measures for older drivers. These included an adaptation of the well validated Useful Field of View (UFOV) and two newer measures, namely a Hazard Perception Test (HPT), and a Hazard Change Detection Task (HCDT). Community dwelling drivers (n=297) aged 65-96 were assessed using a battery of measures of cognitive and visual function. Factor analysis of these predictor variables yielded factors including Executive/Speed, Vision (measured by visual acuity and contrast sensitivity), Spatial, Visual Closure, and Working Memory. Cognitive and Vision factors explained 83-95% of age-related variance in the Capacity to Drive Safely. Spatial and Working Memory were associated with UFOV, HPT and HCDT, Executive/Speed was associated with UFOV and HCDT and Vision was associated with HPT. The Capacity to Drive Safely declines with chronological age, and this decline is associated with age-related declines in several higher order cognitive abilities involving manipulation and storage of visuospatial information under speeded conditions. There are also age-independent effects of cognitive function and vision that determine driving safety. Copyright © 2011 Elsevier Ltd. All rights reserved.
Genetic influences on cognitive decline in Parkinson's disease
Morley, J.F.; Xie, S.X.; Hurtig, H.I.; Stern, M.B.; Colcher, A.; Horn, S.; Dahodwala, N.; Duda, J.E.; Weintraub, D.; Chen-Plotkin, A.S.; Van Deerlin, V.; Falcone, D.; Siderowf, A.
2012-01-01
Background The role of genetic factors in cognitive decline associated with Parkinson's disease is unclear. We examined whether variations in apolipoprotein E, microtubule-associated protein tau or catechol-O-methytransferase genotypes are associated with cognitive decline in Parkinson's disease. Methods We performed a prospective cohort study of 212 patients with a clinical diagnosis of Parkinson's disease. The primary outcome was change in Mattis Dementia Rating Scale version 2 score. Linear mixed-effects models and survival analysis were used to test for associations between genotypes and change in cognitive function over time. Results The ε4 allele of apoliporotein E was associated with more rapid decline (loss of 2.9 (95% CI, 1.7–4.1) more points/year, p<0.001) in total score and an increased risk of a ≥10 pointdrop during the follow-up period (HR 2.8, 95% CI 1.4–5.4, p=0.003). Microtubule-associated protein tau haplotype and catechol-O-methytransferase genotype were associated with measures of memory and attention, respectively, over the entire followup period but not with the overall rate of cognitive decline. Conclusion These results confirm and extend previously described genetic associations with cognitive decline in Parkinson's disease and imply that individual genes may exert effects on specific cognitive domains or at different disease stages. Carrying at least one apolipoprotein E ε4 allele is associated with more rapid cognitive decline in Parkinson's disease, supporting the idea of a component of shared etiology between Parkinson's disease dementia and Alzheimer disease. Clinically, these results suggest genotyping can provide information about the risk of future cognitive decline for Parkinson's disease patients. PMID:22344634
Rouch, Isabelle; Roche, Frédéric; Dauphinot, Virginie; Laurent, Bernard; Antérion, Catherine Thomas; Celle, Sébastien; Krolak-Salmon, Pierre; Barthélémy, Jean-Claude
2012-08-01
Diabetes and impaired fasting glucose, as well as cognitive impairment, are common in the elderly. Although several cross-sectional studies have demonstrated the influence of diabetes on cognitive impairment, only a few longitudinal studies have assessed the relationship between diabetes, impaired fasting glucose and cognitive decline in non-demented elderly community dwellers, by means of extensive neuropsychological batteries. The present study assesses the relationship between baseline diabetes, impaired fasting glucose (IFG) and 2- year evolution of memory, attention and executive performance in a sample of non-demented elderly subjects. Population-based cohort study [(PROgnostic indicator OF cardiovascular and cerebrovascular events (PROOF)]. One hundred and sixty-three community dwellers aged 65 years without dementia at recruitment. Memory, attention and executive performance. A significant association was observed between baseline diabetes mellitus and a higher 2-year decline in the Trial Making Test B and Stroop test exploring attention and executive function. This effect remained significant after adjusting for age, gender, education, anxiety and depressive symptoms, as well as other cardiovascular risk factors (F=2.41; p=0.007). Instead, no relationship was observed between IFG and cognitive decline. Our study showed that, in a sample of elderly non-demented community dwellers, diabetes mellitus (but not IFG) is associated with a higher decline in selective attention and executive functioning. These results emphasize the importance of detecting and man- aging diabetes and impaired fasting glucose, in order to prevent cognitive impairment and dementia.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gondi, Vinai, E-mail: vgondi@chicagocancer.org; University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin; Paulus, Rebecca
Purpose: To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and atmore » 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Results: Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). Conclusions: In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.« less
HDL and Cognition in Neurodegenerative Disorders
Hottman, David A.; Chernick, Dustin; Cheng, Shaowu; Wang, Zhe; Li, Ling
2014-01-01
High-density lipoproteins (HDL) are a heterogeneous group of lipoproteins composed of various lipids and proteins. HDL is formed both in the systemic circulation and in the brain. In addition to being a crucial player in the reverse cholesterol transport pathway, HDL possesses a wide range of other functions including anti-oxidation, anti-inflammation, pro-endothelial function, anti-thrombosis, and modulation of immune function. It has been firmly established that high plasma levels of HDL protect against cardiovascular disease. Accumulating evidence indicates that the beneficial role of HDL extends to many other systems including the central nervous system. Cognition is a complex brain function that includes all aspects of perception, thought, and memory. Cognitive function often declines during aging and this decline manifests as cognitive impairment/dementia in age-related and progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. A growing concern is that no effective therapy is currently available to prevent or treat these devastating diseases. Emerging evidence suggests that HDL may play a pivotal role in preserving cognitive function under normal and pathological conditions. This review attempts to summarize recent genetic, clinical and experimental evidence for the impact of HDL on cognition in aging and in neurodegenerative disorders as well as the potential of HDL-enhancing approaches to improve cognitive function. PMID:25131449
Tanigawa, Takanori; Takechi, Hajime; Arai, Hidenori; Yamada, Minoru; Nishiguchi, Shu; Aoyama, Tomoki
2014-10-01
It is very important to maintain cognitive function in patients with mild cognitive disorder. The aim of the present study was to determine whether the amount of physical activity is associated with memory function in older adults with mild cognitive disorder. A total of 47 older adults with mild cognitive disorder were studied; 30 were diagnosed with mild Alzheimer's disease and 17 with mild cognitive impairment. The global cognitive function, memory function, physical performance and amount of physical activity were measured in these patients. We divided these patients according to their walking speed (<1 m/s or >1 m/s). A total of 26 elderly patients were classified as the slow walking group, whereas 21 were classified as the normal walking group. The normal walking group was younger and had significantly better scores than the slow walking group in physical performance. Stepwise multiple linear regression analysis showed that only the daily step counts were associated with the Scenery Picture Memory Test in patients of the slow walking group (β=0.471, P=0.031), but not other variables. No variable was significantly associated with the Scenery Picture Memory Test in the normal walking group. Memory function was strongly associated with the amount of physical activity in patients with mild cognitive disorder who showed slow walking speed. The results show that lower physical activities could be a risk factor for cognitive decline, and that cognitive function in the elderly whose motor function and cognitive function are declining can be improved by increasing the amount of physical activity. © 2014 Japan Geriatrics Society.
Wu, Chunyuan; Coker, Laura H.; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E.; Rossouw, Jacques E.; Wassertheil-Smoller, Sylvia
2016-01-01
BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS Prospective follow-up of 6,426 cognitively intact women aged 65–79 years enrolled in the Women’s Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140mm Hg or diastolic BP ≥ 90mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 PMID:26137952
Haring, Bernhard; Wu, Chunyuan; Coker, Laura H; Seth, Arjun; Snetselaar, Linda; Manson, JoAnn E; Rossouw, Jacques E; Wassertheil-Smoller, Sylvia
2016-02-01
To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. Prospective follow-up of 6,426 cognitively intact women aged 65-79 years enrolled in the Women's Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP ≥140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90mm Hg (controlled BP). Sodium intake >1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (P for interaction = 0.96 or 0.97). Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Deviation from expected cognitive ability across psychotic disorders.
Hochberger, W C; Combs, T; Reilly, J L; Bishop, J R; Keefe, R S E; Clementz, B A; Keshavan, M S; Pearlson, G D; Tamminga, C A; Hill, S K; Sweeney, J A
2018-02-01
Patients with schizophrenia show a deficit in cognitive ability compared to estimated premorbid and familial intellectual abilities. However, the degree to which this pattern holds across psychotic disorders and is familial is unclear. The present study examined deviation from expected cognitive level in schizophrenia, schizoaffective disorder, and psychotic bipolar disorder probands and their first-degree relatives. Using a norm-based regression approach, parental education and WRAT-IV Reading scores (both significant predictors of cognitive level in the healthy control group) were used to predict global neuropsychological function as measured by the composite score from the Brief Assessment of Cognition in Schizophrenia (BACS) test in probands and relatives. When compared to healthy control group, psychotic probands showed a significant gap between observed and predicted BACS composite scores and a greater likelihood of robust cognitive decline. This effect was not seen in unaffected relatives. While BACS and WRAT-IV Reading scores were themselves highly familial, the decline in cognitive function from expectation had lower estimates of familiality. Thus, illness-related factors such as epigenetic, treatment, or pathophysiological factors may be important causes of illness related decline in cognitive abilities across psychotic disorders. This is consistent with the markedly greater level of cognitive impairment seen in affected individuals compared to their unaffected family members. Copyright © 2017 Elsevier B.V. All rights reserved.
Cognitive effects of exogenous melatonin administration in elderly persons: a pilot study.
Peck, Joel S; LeGoff, Daniel B; Ahmed, Iqbal; Goebert, Deborah
2004-01-01
Given that circadian rhythm disruption is associated with impairments in cognitive performance similar to those found in age-related cognitive decline, the authors investigated whether exogenous melatonin administration would improve cognitive functioning in healthy elderly subjects. This double-blind, placebo-controlled pilot study assigned 26 healthy elderly subjects to receive either melatonin 1 mg or placebo nightly for 4 weeks. Participants completed a sleep questionnaire and a battery of cognitive tests at baseline and at 4 weeks. Melatonin administration improved reported morning "restedness" and sleep latency after nocturnal awakening, and also improved scores on the California Verbal Learning Test-interference subtest. Melatonin administration at a dose of 1 mg nightly may be effective in improving certain aspects of cognitive functioning and subjective reports of sleep quality in elderly subjects. It may prove to be a useful therapeutic agent in the treatment of age-related cognitive decline.
Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)
Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.
2011-01-01
An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function. PMID:21315756
Alzheimer's disease and age-related memory decline (preclinical).
Terry, Alvin V; Callahan, Patrick M; Hall, Brandon; Webster, Scott J
2011-08-01
An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function. Copyright © 2011 Elsevier Inc. All rights reserved.
Bock, Meredith; Duong, Y-Nhy; Kim, Anthony; Allen, Isabel; Murphy, Jennifer; Lomen-Hoerth, Catherine
2017-12-01
To prospectively evaluate the progression of cognitive-behavioral function in amyotrophic lateral sclerosis (ALS) and examine the association of cognitive-behavioral deficits with disease progression, patient quality of life (QOL), and caregiver burden. We evaluated cognitive-behavioral function using the Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen at enrollment and after 7 months in a cohort of patients with ALS. Paired t tests were used to evaluate the change in the 2 assessments. Linear regression and Kruskal-Wallis tests were applied to investigate how initial cognitive or behavioral status related to outcomes. The mean test-retest interval was 6.8 months (SD 1.6). Cognitive status of the study population (n = 49) overall did not change over the study period ( p = 0.06) despite progression of motor weakness ( p < 0.001), though small subsets of the sample demonstrate cognitive change. Patients initially classified as behaviorally normal showed increased behavioral problems over time ( t = -2.8, p = 0.009). Decline in cognitive (β = -1.3, p = 0.03) and behavioral (β = -0.76, p = 0.002) status predicted increasing caregiver burden. Behavioral abnormalities predicted decline in forced vital capacity and ALS Functional Rating Scale-Revised score ( p = 0.008, 0.012) in the study population and patient QOL in the most severely affected group ( t = 4.3, p = 0.003). Cognitive-behavioral change is a key aspect of disease heterogeneity in ALS. Executive function in ALS overall remains stable over 7 months as detected by an administered screening tool. However, patients may develop caregiver-reported behavioral symptoms in that time period. Screening for caregiver-reported symptoms has a particular utility in predicting future clinical decline, increased caregiver burden, and worsening patient QOL.
A randomized controlled trial of Kundalini yoga in mild cognitive impairment
Eyre, Harris A.; Siddarth, Prabha; Acevedo, Bianca; Van Dyk, Kathleen; Paholpak, Pattharee; Ercoli, Linda; Cyr, Natalie St.; Yang, Hongyu; Khalsa, Dharma S.; Lavretsky, Helen
2017-01-01
Background Global population aging will result in increasing rates of cognitive decline and dementia. Thus, effective, low-cost, and low side-effect interventions for the treatment and prevention of cognitive decline are urgently needed. Our study is the first to investigate the effects of Kundalini yoga (KY) training on mild cognitive impairment (MCI). Methods Older participants (≥55 years of age) with MCI were randomized to either a 12-week KY intervention or memory enhancement training (MET; gold-standard, active control). Cognitive (i.e. memory and executive functioning) and mood (i.e. depression, apathy, and resilience) assessments were administered at baseline, 12 weeks and 24 weeks. Results At baseline, 81 participants had no significant baseline group differences in clinical or demographic characteristics. At 12 weeks and 24 weeks, both KY and MET groups showed significant improvement in memory; however, only KY showed significant improvement in executive functioning. Only the KY group showed significant improvement in depressive symptoms and resilience at week 12. Conclusion KY group showed short- and long-term improvements in executive functioning as compared to MET, and broader effects on depressed mood and resilience. This observation should be confirmed in future clinical trials of yoga intervention for treatment and prevention of cognitive decline (NCT01983930). PMID:28088925
USDA-ARS?s Scientific Manuscript database
Research in both human and animals has demonstrated that cognitive function decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. These functional declines may be caused by long-term increases in and susceptibility to oxidative stress and infl...
USDA-ARS?s Scientific Manuscript database
Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...
Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS.
Foley, Jennifer A; Foltynie, Tom; Zrinzo, Ludvic; Hyam, Jonathan A; Limousin, Patricia; Cipolotti, Lisa
2017-01-01
Objective . Reduced verbal fluency is a strikingly uniform finding following deep brain stimulation (DBS) for Parkinson's disease (PD). The precise cognitive mechanism underlying this reduction remains unclear, but theories have suggested reduced motivation, linguistic skill, and/or executive function. It is of note, however, that previous reports have failed to consider the potential role of any changes in speed of processing. Thus, the aim of this study was to examine verbal fluency changes with a particular focus on the role of cognitive speed. Method . In this study, 28 patients with PD completed measures of verbal fluency, motivation, language, executive functioning, and speed of processing, before and after DBS. Results . As expected, there was a marked decline in verbal fluency but also in a timed test of executive functions and two measures of speed of processing. Verbal fluency decline was associated with markers of linguistic and executive functioning, but not after speed of processing was statistically controlled for. In contrast, greater decline in verbal fluency was associated with higher levels of apathy at baseline, which was not associated with changes in cognitive speed. Discussion . Reduced generativity and processing speed may account for the marked reduction in verbal fluency commonly observed following DBS.
Hsu, Chun Liang; Best, John R.; Chiu, Bryan K.; Nagamatsu, Lindsay S; Voss, Michelle W.; Handy, Todd C.; Bolandzadeh, Niousha; Liu-Ambrose, Teresa
2016-01-01
Impaired mobility, such as falls, may be an early biomarker of subsequent cognitive decline and is associated with subclinical alterations in both brain structure and function. In this 12-month prospective study, we examined whether there are volumetric differences in gray matter and subcortical regions, as well as cerebral white matter, between older fallers and non-fallers. In addition, we assessed whether these baseline volumetric differences are associated with changes in cognitive function over 12 months. A total of 66 community-dwelling older adults were recruited and categorized by their falls status. Magnetic resonance imaging occurred at baseline and participants’ physical and cognitive performances were assessed at baseline and 12-months. At baseline, fallers showed significantly lower volumes in gray matter, subcortical regions, and cerebral white matter compared with non-fallers. Notably, fallers had significantly lower left lateral orbitofrontal white matter volume. Moreover, lower left lateral orbitofrontal white matter volume at baseline was associated with greater decline in set-shifting performance over 12 months. Our data suggest that falls may indicate subclinical alterations in regional brain volume that are associated with subsequent decline in executive functions. PMID:27079333
Williamson, Jeff D.; Launer, Lenore J.; Bryan, R. Nick; Coker, Laura H.; Lazar, Ronald M.; Gerstein, Hertzel C.; Murray, Anne M.; Sullivan, Mark D.; Horowitz, Karen R.; Ding, Jingzhong; Marcovina, Santica; Lovato, Laura; Lovato, James; Margolis, Karen L.; Davatzikos, Christos; Barzilay, Joshua; Ginsberg, Henry N.; Linz, Peter E.; Miller, Michael E.
2015-01-01
IMPORTANCE Persons with type 2 diabetes mellitus (T2DM) are at increased risk for decline in cognitive function, reduced brain volume, and increased white matter lesions in the brain. Poor control of blood pressure (BP) and lipid levels are risk factors for T2DM-related cognitive decline, but the effect of intensive treatment on brain function and structure is unknown. OBJECTIVE To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume (TBV) in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c (HbA1c) levels less than 7.5% randomized to a systolic BP goal of less than 120 vs less than 140 mm Hg (n = 1439) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL (n = 1538). Participants were recruited from August 1, 2003, through October 31, 2005, with the final follow-up visit by June 30, 2009. MAIN OUTCOME MEASURES Cognition was assessed at baseline and 20 and 40 months. A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health. RESULTS Baseline mean HbA1c level was 8.3%; mean age, 62 years; and mean duration of T2DM, 10 years. At 40 months, no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial. At 40 months, TBV had declined more in the intensive vs standard BP-lowering group (difference, −4.4 [95% CI, −7.8 to −1.1] cm3; P = .01). Fibrate therapy had no effect on TBV compared with placebo. CONCLUSIONS AND RELEVANCE In participants with long-standing T2DM and at high risk for cardiovascular events, intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up. Intensive BP control was associated with greater decline in TBV at 40 months relative to standard therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00000620 PMID:24493100
Yun, Richard J; Krystal, John H; Mathalon, Daniel H
2010-03-01
The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.
Cognitive Trajectory Changes Over 20 Years Before Dementia Diagnosis: A Large Cohort Study.
Li, Ge; Larson, Eric B; Shofer, Jane B; Crane, Paul K; Gibbons, Laura E; McCormick, Wayne; Bowen, James D; Thompson, Mary Lou
2017-12-01
Longitudinal studies have shown an increase in cognitive decline many years before clinical diagnosis of dementia. We sought to estimate changes, relative to "normal" aging, in the trajectory of scores on a global cognitive function test-the Cognitive Abilities Screening Instrument (CASI). A prospective cohort study. Community-dwelling members of a U.S. health maintenance organization. Individuals aged 65 and older who had no dementia diagnosis at baseline and had at least two visits with valid CASI test score (N = 4,315). Average longitudinal trajectories, including changes in trajectory before clinical diagnosis in those who would be diagnosed with dementia, were estimated for CASI item response theory (IRT) scores. The impact of sex, education level, and APOE genotype on cognitive trajectories was assessed. Increased cognitive decline relative to "normal" aging was evident in CASI IRT at least 10 years before clinical diagnosis. Male gender, lower education, and presence of ≥1 APOE ε4 alleles were associated with lower average IRT scores. In those who would be diagnosed with dementia, a trajectory change point was estimated at an average of 3.1 years (95% confidence interval 3.0-3.2) before clinical diagnosis, after which cognitive decline appeared to accelerate. The change point did not differ by sex, education level, or APOE ε4 genotype. There were subtle differences in trajectory slopes by sex and APOE ε4 genotype, but not by education. Decline in average global cognitive function was evident at least 10 years before clinical diagnosis of dementia. The decline accelerated about 3 years before clinical diagnosis. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.
Moving Forward: Age Effects on the Cerebellum Underlie Cognitive and Motor Declines
Bernard, Jessica A.; Seidler, Rachael D.
2014-01-01
Though the cortical contributions to age-related declines in motor and cognitive performance are well-known, the potential contributions of the cerebellum are less clear. The diverse functions of the cerebellum make it an important structure to investigate in aging. Here, we review the extant literature on this topic. To date, there is evidence to indicate that there are morphological age differences in the cerebellum that are linked to motor and cognitive behavior. Cerebellar morphology is often as good as -- or even better -- at predicting performance than the prefrontal cortex. We also touch on the few studies using functional neuroimaging and connectivity analyses that further implicate the cerebellum in age-related performance declines. Importantly, we provide a conceptual framework for the cerebellum influencing age differences in performance, centered on the notion of degraded internal models. The evidence indicating that cerebellar age differences associate with performance highlights the need for additional work in this domain to further elucidate the role of the cerebellum in age differences in movement control and cognitive function. PMID:24594194
Cruz, L; Roe, D L; Urbanc, B; Inglis, A; Stanley, H E; Rosene, D L
2009-02-18
The age-related decline in cognitive function that is observed in normal aging monkeys and humans occurs without significant loss of cortical neurons. This suggests that cognitive impairment results from subtle, sub-lethal changes in the cortex. Recently, changes in the structural coherence in mini- or microcolumns without loss of neurons have been linked to loss of function. Here we use a density map method to quantify microcolumnar structure in both banks of the sulcus principalis (prefrontal cortical area 46) of 16 (ventral) and 19 (dorsal) behaviorally tested female rhesus monkeys from 6 to 33 years of age. While total neuronal density does not change with age in either of these banks, there is a significant age-related reduction in the strength of microcolumns in both regions on the order of 40%. This likely reflects a subtle but definite loss of organization in the structure of the cortical microcolumn. The reduction in strength in ventral area 46 correlates with cognitive impairments in learning and memory while the reduction in dorsal area 46 does not. This result is congruent with published data attributing cognitive functions to ventral area 46 that are similar to our particular cognitive battery which does not optimally tap cognitive functions attributed to dorsal area 46. While the exact mechanisms underlying this loss of microcolumnar organization remain to be determined, it is plausible that they reflect age-related alterations in dendritic and/or axonal organization which alter connectivity and may contribute to age-related declines in cognitive performance.
Positive affect and cognitive decline: a 12-year follow-up of the Maastricht Aging Study.
Berk, Lotte; van Boxtel, Martin; Köhler, Sebastian; van Os, Jim
2017-12-01
In cross-sectional studies, positive affect (PA) has been associated with higher levels of cognitive functioning. This study examined whether positive affect (PA) is associated with change in cognitive function over 12 years in an adult population sample. Participants (n = 258), aged 40 to 82 years, were drawn from a subsample of the Maastricht Aging Study (MAAS) and assessed at baseline, 6 years and 12 years. PA was measured at baseline with a Dutch translation of the Positive and Negative Affect Schedule (PANAS). PA scores and associations with cognitive decline were tested in random-effects models. Controlling for demographics and depressive symptoms, there was no significant association with PA scores and decline in memory (χ 2 = 1.52; df = 2; P = 0.47), executive functions (χ 2 = 0.99; df = 2; P = 0.61), and information processing speed (χ 2 = 0.52; df = 2; P = 0.77) at 6- and 12-year follow-up. PA did not predict cognitive change over time. These findings question the extent of protective effects of PA on cognitive aging in adulthood, and are discussed in terms of age range and types of measures used for PA and cognition. Copyright © 2016 John Wiley & Sons, Ltd.
Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues.
Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K
2016-03-01
Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets.
Association of socioeconomic status and cognitive functioning change among elderly Chinese people.
Yang, Lei; Martikainen, Pekka; Silventoinen, Karri; Konttinen, Hanna
2016-09-01
the inverse association between high socioeconomic status and impaired cognitive functioning in old age has been widely studied. However, it is still inconclusive whether higher socioeconomic status slows the rate of cognitive decline over ageing, especially in non-Western populations. We examined this association using a large population-based longitudinal survey of older Chinese persons. the sample came from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) (from the years 2002 to 2011, N = 15,798 at baseline, aged 65-105). The Mini-Mental State Examination (MMSE) based on face-to-face interviews was used to assess cognitive functioning. Socioeconomic status was assessed using educational attainment and household income per capita. Latent growth curve and selection model considering the attrition during the follow-up were utilised to assess the effect of socioeconomic status on the rate of change in cognitive functioning. at baseline, younger elderly people, urban residents and elderly people living alone had better cognitive performance in both genders. Educational attainment was positively associated with cognitive functioning at baseline but did not have a significant effect on the rate of change in cognitive functioning. Higher incomes were associated with better cognitive functioning at baseline, but this difference diminished during the follow-up. higher socioeconomic status was associated with better cognitive performance at baseline but could not protect against the rate of decline in cognitive functioning measured by MMSE in this longitudinal study for elderly Chinese people. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.
2018-01-01
The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.
Physical Fitness and Serum Vitamin D and Cognition in Elderly Koreans.
Ahn, Jeong-Deok; Kang, Hyunsik
2015-12-01
Poor physical fitness and low serum vitamin D are known to be modifiable risk factors for cognitive declines with normal aging. We investigated the association of physical fitness and serum vitamin D levels with global cognitive function in older adults. In this cross-sectional study, a total of 412 older Korean adults (108 men aged 74.4 ± 6.0 years and 304 women aged 73.1 ± 5.4 years) completed the Korean version of Mini-Mental State Examination (MMSE) to assess global cognitive performance and the senior fitness test to assess strength, flexibility, agility, and endurance domains of physical fitness. Body mass index, percent body fat, serum vitamin D, geriatric depression scale (GDS), level of education, smoking, and history of cardiovascular or cerebrovascular disease were also assessed as covariates. Age, sex, GDS, and body fatness were negatively associated with MMSE-based cognitive performance. Serum vitamin D and physical fitness were positively associated with MMSE-based cognitive performance. Multivariate linear regression showed that agility (partial R(2) = -0.184, p = 0.029) and endurance (partial R(2) = 0.191, p = 0.022) domains of physical fitness along with serum vitamin D (partial R(2) = 0.210, p = 0.012) were significant predictors for global cognitive performance after controlling for covariates (i.e., age, sex, education, GDS, body fatness, and comorbidity index). The current findings of the study suggest that promotion of physical fitness and vitamin D supplementation should be key components of interventions to prevent cognitive decline with normal aging. Key pointsCognitive declines are associated with normal aging as well as modifiable lifestyle risk factors, and there is an increasing need to identify the modifiable risk factors for the onset of cognitive declines and to provide evidence-based strategies for healthy and successful aging.In Korea, little is known about the relationships of physical fitness and serum vitamin D with cognitive function in older adults, and we determined the associations between a) serum vitamin D levels and cognitive function and b) physical fitness and cognitive function among community-dwelling elderly Koreans.The current findings of the study suggest that agility and endurance domains of physical fitness along with serum vitamin D were significant predictors for global cognitive performance after controlling for covariates.
Physical Fitness and Serum Vitamin D and Cognition in Elderly Koreans
Ahn, Jeong-Deok; Kang, Hyunsik
2015-01-01
Poor physical fitness and low serum vitamin D are known to be modifiable risk factors for cognitive declines with normal aging. We investigated the association of physical fitness and serum vitamin D levels with global cognitive function in older adults. In this cross-sectional study, a total of 412 older Korean adults (108 men aged 74.4 ± 6.0 years and 304 women aged 73.1 ± 5.4 years) completed the Korean version of Mini-Mental State Examination (MMSE) to assess global cognitive performance and the senior fitness test to assess strength, flexibility, agility, and endurance domains of physical fitness. Body mass index, percent body fat, serum vitamin D, geriatric depression scale (GDS), level of education, smoking, and history of cardiovascular or cerebrovascular disease were also assessed as covariates. Age, sex, GDS, and body fatness were negatively associated with MMSE-based cognitive performance. Serum vitamin D and physical fitness were positively associated with MMSE-based cognitive performance. Multivariate linear regression showed that agility (partial R2 = -0.184, p = 0.029) and endurance (partial R2 = 0.191, p = 0.022) domains of physical fitness along with serum vitamin D (partial R2 = 0.210, p = 0.012) were significant predictors for global cognitive performance after controlling for covariates (i.e., age, sex, education, GDS, body fatness, and comorbidity index). The current findings of the study suggest that promotion of physical fitness and vitamin D supplementation should be key components of interventions to prevent cognitive decline with normal aging. Key points Cognitive declines are associated with normal aging as well as modifiable lifestyle risk factors, and there is an increasing need to identify the modifiable risk factors for the onset of cognitive declines and to provide evidence-based strategies for healthy and successful aging. In Korea, little is known about the relationships of physical fitness and serum vitamin D with cognitive function in older adults, and we determined the associations between a) serum vitamin D levels and cognitive function and b) physical fitness and cognitive function among community-dwelling elderly Koreans. The current findings of the study suggest that agility and endurance domains of physical fitness along with serum vitamin D were significant predictors for global cognitive performance after controlling for covariates. PMID:26664270
The Influence of Executive Functioning on Facial and Subjective Pain Responses in Older Adults
2016-01-01
Cognitive decline is known to reduce reliability of subjective pain reports. Although facial expressions of pain are generally considered to be less affected by this decline, empirical support for this assumption is sparse. The present study therefore examined how cognitive functioning relates to facial expressions of pain and whether cognition acts as a moderator between nociceptive intensity and facial reactivity. Facial and subjective responses of 51 elderly participants to mechanical stimulation at three intensities levels (50 kPa, 200 kPa, and 400 kPa) were assessed. Moreover, participants completed a neuropsychological examination of executive functioning (planning, cognitive inhibition, and working memory), episodic memory, and psychomotor speed. The results showed that executive functioning has a unique relationship with facial reactivity at low pain intensity levels (200 kPa). Moreover, cognitive inhibition (but not other executive functions) moderated the effect of pressure intensity on facial pain expressions, suggesting that the relationship between pressure intensity and facial reactivity was less pronounced in participants with high levels of cognitive inhibition. A similar interaction effect was found for cognitive inhibition and subjective pain report. Consequently, caution is needed when interpreting facial (as well as subjective) pain responses in individuals with a high level of cognitive inhibition. PMID:27274618
Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.
Hohman, Timothy J; Tommet, Doug; Marks, Shawn; Contreras, Joey; Jones, Rich; Mungas, Dan
2017-10-01
Age-related changes in cognition are partially mediated by the presence of neuropathology and neurodegeneration. This manuscript evaluates the degree to which biomarkers of Alzheimer's disease, (AD) neuropathology and longitudinal changes in brain structure, account for age-related differences in cognition. Data from the AD Neuroimaging Initiative (n = 1012) were analyzed, including individuals with normal cognition and mild cognitive impairment. Parallel process mixed effects regression models characterized longitudinal trajectories of cognitive variables and time-varying changes in brain volumes. Baseline age was associated with both memory and executive function at baseline (p's < 0.001) and change in memory and executive function performances over time (p's < 0.05). After adjusting for clinical diagnosis, baseline, and longitudinal changes in brain volume, and baseline levels of cerebrospinal fluid biomarkers, age effects on change in episodic memory and executive function were fully attenuated, age effects on baseline memory were substantially attenuated, but an association remained between age and baseline executive function. Results support previous studies that show that age effects on cognitive decline are fully mediated by disease and neurodegeneration variables but also show domain-specific age effects on baseline cognition, specifically an age pathway to executive function that is independent of brain and disease pathways. Copyright © 2017 Elsevier Inc. All rights reserved.
Digging Into the Mysteries of Delirium | NIH MedlinePlus the Magazine
... from dementia? Delirium is an acute change in cognitive function, primarily characterized by confusion and which may wax ... wane—whereas dementia is a progressive decline in cognitive function that occurs over months and years. Does delirium ...
Kuiper, Jisca S; Zuidersma, Marij; Zuidema, Sytse U; Burgerhof, Johannes Gm; Stolk, Ronald P; Oude Voshaar, Richard C; Smidt, Nynke
2016-08-01
Although poor social relationships are assumed to contribute to cognitive decline, meta-analytic approaches have not been applied. Individual study results are mixed and difficult to interpret due to heterogeneity in measures of social relationships. We conducted a systematic review and meta-analysis to investigate the relation between poor social relationships and cognitive decline. MEDLINE, Embase and PsycINFO were searched for longitudinal cohort studies examining various aspects of social relationships and cognitive decline in the general population. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using random effects meta-analysis. Sources of heterogeneity were explored and likelihood of publication bias was assessed. We stratified analyses according to three aspects of social relationships: structural, functional and a combination of these. We identified 43 articles. Poor social relationships predicted cognitive decline; for structural (19 studies): pooled OR: 1.08 (95% CI: 1.05-1.11); functional (8 studies): pooled OR: 1.15 (95% CI: 1.00-1.32); and combined measures (7 studies): pooled OR: 1.12 (95% CI: 1.01-1.24). Meta-regression and subgroup analyses showed that the heterogeneity could be explained by the type of social relationship measurement and methodological quality of included studies. Despite heterogeneity in study design and measures, our meta-analyses show that multiple aspects of social relationships are associated with cognitive decline. As evidence for publication bias was found, the association might be overestimated and should therefore be interpreted with caution. Future studies are needed to better define the mechanisms underlying these associations. Potential causality of this prognostic association should be examined in future randomized controlled studies. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
Kynast, Jana; Lampe, Leonie; Luck, Tobias; Frisch, Stefan; Arelin, Katrin; Hoffmann, Karl-Titus; Loeffler, Markus; Riedel-Heller, Steffi G; Villringer, Arno; Schroeter, Matthias L
2018-06-01
Age-related white matter hyperintensities (WMH) are a manifestation of white matter damage seen on magnetic resonance imaging (MRI). They are related to vascular risk factors and cognitive impairment. This study investigated the cognitive profile at different stages of WMH in a large community-dwelling sample; 849 subjects aged 21 to 79 years were classified on the 4-stage Fazekas scale according to hyperintense lesions seen on individual T2-weighted fluid-attenuated inversion recovery MRI scans. The evaluation of cognitive functioning included seven domains of cognitive performance and five domains of subjective impairment, as proposed by the DSM-5. For the first time, the impact of age-related WMH on Theory of Mind was investigated. Differences between Fazekas groups were analyzed non-parametrically and effect sizes were computed. Effect sizes revealed a slight overall cognitive decline in Fazekas groups 1 and 2 relative to healthy subjects. Fazekas group 3 presented substantial decline in social cognition, attention and memory, although characterized by a high inter-individual variability. WMH groups reported subjective cognitive decline. We demonstrate that extensive WMH are associated with specific impairment in attention, memory, social cognition, and subjective cognitive performance. The detailed neuropsychological characterization of WMH offers new therapeutic possibilities for those affected by vascular cognitive decline.
Cognitive decline in Parkinson disease
Aarsland, Dag; Creese, Byron; Politis, Marios; Chaudhuri, K. Ray; ffytche, Dominic H.; Weintraub, Daniel; Ballard, Clive
2017-01-01
Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results. PMID:28257128
Zahodne, Laura B; Stern, Yaakov; Manly, Jennifer J
2015-07-01
In light of growing debate over whether and how early life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. Older adults (N = 3,435) in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. More years of education were associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. Although having additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., 9 years and beyond) is associated with higher income, which may influence late-life cognitive health through multiple, nonmutually exclusive pathways. (c) 2015 APA, all rights reserved).
Zahodne, Laura B.; Stern, Yaakov; Manly, Jennifer J.
2014-01-01
Objective In light of growing debate over whether and how early-life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. Method 3,435 older adults in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. Results More years of education was associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. While additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. Conclusions Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., beyond 9 years) is associated with higher income, which may influence late-life cognitive health through multiple, non-mutually exclusive pathways. PMID:25222199
Patron, Elisabetta; Messerotti Benvenuti, Simone; Zanatta, Paolo; Polesel, Elvio; Palomba, Daniela
2013-01-01
To examine whether preoperative psychological dysfunctions rather than intraoperative factors may differentially predict short- and long-term postoperative cognitive decline (POCD) in patients after cardiac surgery. Forty-two patients completed a psychological evaluation, including the Trail Making Test Part A and B (TMT-A/B), the memory with 10/30-s interference, the phonemic verbal fluency and the Center for Epidemiological Studies of Depression (CES-D) scale for cognitive functions and depressive symptoms, respectively, before surgery, at discharge and at 18-month follow-up. Ten (24%) and 11 (26%) patients showed POCD at discharge and at 18-month follow-up, respectively. The duration of cardiopulmonary bypass significantly predicted short-term POCD [odds ratio (OR)=1.04, P<.05], whereas preoperative psychological factors were unrelated to cognitive decline at discharge. Conversely, long-term cognitive decline after cardiac surgery was significantly predicted by preoperative scores in the CES-D (OR=1.26, P<.03) but not by intraoperative variables (all Ps >.23). Our findings showed that preexisting depressive symptoms rather than perioperative risk factors are associated with cognitive decline 18 months after cardiac surgery. This study suggests that a preoperative psychological evaluation of depressive symptoms is essential to anticipate which patients are likely to show long-term cognitive decline after cardiac surgery. Copyright © 2013 Elsevier Inc. All rights reserved.
Innes, Kim E; Selfe, Terry Kit; Khalsa, Dharma Singh; Kandati, Sahiti
2017-01-01
While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive, evidence suggests mind-body interventions may hold promise. In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer's disease. Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for 3 months, then at their discretion for the ensuing 3 months. At baseline, 3 months, and 6 months we measured memory and cognitive functioning [Memory Functioning Questionnaire (MFQ), Trail-making Test (TMT-A/B), and Digit-Symbol Substitution Test (DSST)]. The 6-month study was completed by 53 participants (88%). Participants performed an average of 93% (91% KK, 94% ML) of sessions in the first 3 months, and 71% (68% KK, 74% ML) during the 3-month, practice-optional, follow-up period. Both groups showed marked and significant improvements at 3 months in memory and cognitive performance (MFQ, DSST, TMT-A/B; p's≤0.04). At 6 months, overall gains were maintained or improved (p's≤0.006), with effect sizes ranging from medium (DSST, ML group) to large (DSST, KK group; TMT-A/B, MFQ). Changes were unrelated to treatment expectancies and did not differ by age, gender, baseline cognition scores, or other factors. Findings of this preliminary randomized controlled trial suggest practice of meditation or ML can significantly enhance both subjective memory function and objective cognitive performance in adults with SCD, and may offer promise for improving outcomes in this population.
Association of vascular risk factors with cognition in a multiethnic sample.
Schneider, Brooke C; Gross, Alden L; Bangen, Katherine J; Skinner, Jeannine C; Benitez, Andreana; Glymour, M Maria; Sachs, Bonnie C; Shih, Regina A; Sisco, Shannon; Manly, Jennifer J; Luchsinger, José A
2015-07-01
To examine the relationship between cardiovascular risk factors (CVRFs) and cognitive performance in a multiethnic sample of older adults. We used longitudinal data from the Washington Heights-Inwood Columbia Aging Project. A composite score including smoking, stroke, heart disease, diabetes, hypertension, and central obesity represented CVRFs. Multiple group parallel process multivariate random effects regression models were used to model cognitive functioning and examine the contribution of CVRFs to baseline performance and change in general cognitive processing, memory, and executive functioning. Presence of each CVRF was associated with a 0.1 SD lower score in general cognitive processing, memory, and executive functioning in black and Hispanic participants relative to whites. Baseline CVRFs were associated with poorer baseline cognitive performances among black women and Hispanic men. CVRF increase was related to baseline cognitive performance only among Hispanics. CVRFs were not related to cognitive decline. After adjustment for medications, CVRFs were not associated with cognition in Hispanic participants. CVRFs are associated with poorer cognitive functioning, but not cognitive decline, among minority older adults. These relationships vary by gender and medication use. Consideration of unique racial, ethnic, and cultural factors is needed when examining relationships between CVRFs and cognition. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Like cognitive function, decision making across the life span shows profound age-related changes.
Tymula, Agnieszka; Rosenberg Belmaker, Lior A; Ruderman, Lital; Glimcher, Paul W; Levy, Ifat
2013-10-15
It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain.
2012-01-01
Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging. PMID:22537877
Regular use of nonsteroidal anti-inflammatory drugs and cognitive function in aging women.
Kang, Jae Hee; Grodstein, Francine
2003-05-27
To examine the relationship of nonsteroidal anti-inflammatory drug (NSAID) use and cognitive decline in young-old women. The authors prospectively studied 16,128 Nurses' Health Study participants, aged 70 to 81 years at baseline, who provided information on NSAID use and potential confounders in biennial questionnaires from 1976 through 1998. From 1995 through 2001, we administered, by telephone, six tests of cognitive function, including the Telephone Interview of Cognitive Status (TICS). Second interviews were begun 2 years later and completed on 13,255 women to date. The authors used multiple logistic regression to estimate relative risks (RR) of low baseline scores (defined as the bottom 10%) and substantial decline (worst 10%). Compared to never users, the RR was 0.75 (95% CI 0.59, 0.96) for a low baseline TICS score with current aspirin use of 15+ years duration, and 0.79 (95% CI 0.62, 1.02) for current use of NSAID (primarily ibuprofen) lasting 8+ years. Results for aspirin users were weaker on other tests, but long-term ibuprofen users had a RR of 0.75 (95% CI 0.56, 1.00) for a low baseline global score (combination of all six tests). The RR for substantial global cognitive decline was 0.93 (95% CI 0.68, 1.26) with long-term aspirin use, and 0.77 (95% CI 0.57, 1.05) with long-term ibuprofen use. In these young-old women, current, long-term NSAID users, especially of nonaspirin agents, showed reduced odds of low cognitive function and possibly lower rates of substantial cognitive decline over 2 years. Continued follow-up will help determine if associations differ at older ages.
Perceived Social Isolation and Cognition
Cacioppo, John T.; Hawkley, Louise C.
2009-01-01
Social species, from Drosophila melanogaster to Homo sapiens, fare poorly when isolated. Homo sapiens, an irrepressibly meaning-making species, are, in normal circumstances, dramatically affected by perceived social isolation. Research indicates that perceived social isolation (i.e., loneliness) is a risk factor for, and may contribute to, poorer overall cognitive performance, faster cognitive decline, poorer executive functioning, more negativity and depressive cognition, heightened sensitivity to social threats, a confirmatory bias in social cognition that is self-protective and paradoxically self-defeating, heightened anthropomorphism, and contagion that threatens social cohesion. These differences in attention and cognition impact emotions, decisions, behaviors, and interpersonal interactions that may contribute to the association between loneliness and cognitive decline and between loneliness and morbidity more generally. PMID:19726219
Conrad, Cheryl D; Bimonte-Nelson, Heather A
2010-01-01
Life expectancies have increased substantially in the last century, dramatically amplifying the proportion of individuals who will reach old age. As individuals age, cognitive ability declines, although the rate of decline differs amongst the forms of memory domains and for different individuals. Memory domains especially impacted by aging are declarative and spatial memories. The hippocampus facilitates the formation of declarative and spatial memories. Notably, the hippocampus is particularly vulnerable to aging. Genetic predisposition and lifetime experiences and exposures contribute to the aging process, brain changes and subsequent cognitive outcomes. In this review, two factors to which an individual is exposed, the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-gonadal (HPG) axis, will be considered regarding the impact of age on hippocampal-dependent function. Spatial memory can be affected by cumulative exposure to chronic stress via glucocorticoids, released from the HPA axis, and from gonadal steroids (estrogens, progesterone and androgens) and gonadotrophins, released from the HPG axis. Additionally, this review will discuss how these hormones impact age-related hippocampal function. We hypothesize that lifetime experiences and exposure to these hormones contribute to the cognitive makeup of the aged individual, and contribute to the heterogeneous aged population that includes individuals with cognitive abilities as astute as their younger counterparts, as well as individuals with severe cognitive decline or neurodegenerative disease. Copyright 2010 Elsevier B.V. All rights reserved.
Association between late-onset depression and incident dementia in Chinese older persons.
Tam, C W C; Lam, L C W
2013-12-01
OBJECTIVE. Previous studies have shown that depression is a precursor / prodrome or susceptible state for the development of dementia. This study aimed to examine the relationship between late-onset depression and subsequent cognitive and functional decline in a cohort of non-demented older Chinese persons at their 2-year follow-up and investigate for possible predictors of cognitive decline. METHODS. A total of 81 depressed subjects and 468 non-depressed community controls were recruited. RESULTS. Subjects with late-onset depression showed significantly more incident Clinical Dementia Rating (CDR) scale decline (odds ratio = 3.87, 95% confidence interval = 2.23-6.70) and dementia (odds ratio = 3.44, 95% confidence interval = 1.75-6.77) than those without depression. A higher proportion of depressed CDR 0 subjects had CDR and functional decline than their non-depressed counterparts. Depressed CDR 0.5 subjects had significantly higher rates of functional decline and lower rates of improvement in CDR than their non-depressed counterparts. CONCLUSION. Diagnosis of depression was a robust predictor of incident very mild dementia (i.e. CDR of 0.5) and depression severity was a predictor of progression to dementia from CDR of 0.5. The association between depression and the risk of CDR decline and dementia was observed in non-demented Chinese subjects. Depression was also associated with persistent mild cognitive deficits in CDR 0.5 subjects.
Ability of university-level education to prevent age-related decline in emotional intelligence
Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo
2014-01-01
Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging. PMID:24653697
Umegaki, Hiroyuki; Iimuro, Satoshi; Shinozaki, Tomohiro; Araki, Atsushi; Sakurai, Takashi; Iijima, Katsuya; Ohashi, Yasuo; Ito, Hideki
2012-04-01
Considerable attention has been paid to the association between type 2 diabetes mellitus (T2DM) and cognitive dysfunction in the elderly. T2DM is often comorbid with several other metabolic disturbances, including hypertension and dyslipidemia. These comorbid diseases might be associated with cognitive impairment. Many clinical indices should be included as variables for the association with cognitive decline. In the current study, we tried to identify the associated factors with cognitive decline during a 6-year period in elderly T2DM considering the changes in the clinical indices during the follow-up period. The subjects in the present study were 63 Japanese Elderly Interventional Trial participants who were administered the Mini-Mental State Examination at baseline, at the third year, and at the end of the 6-year follow-up period. We applied the pooled logistic analysis method to consider the changes in clinical indices during the observation period and tried to identify the factors associated with cognitive decline during the 6 years in elderly type 2 diabetics using repeated measured data for glycated hemoglobin A1c, blood pressure and serum lipids. In the current study, low high-density lipoprotein-cholesterol and higher diastolic blood pressure were significantly associated with cognitive decline by pooled logistic analysis in the 6-year observation of older diabetic subjects. Higher glycated hemoglobin A1c had a tendency toward association with cognitive decline. The results suggest that comprehensive management of diabetes, including dyslipidemia and hypertension, might contribute to the prevention of declines in cognitive function in older diabetic patients. © 2012 Japan Geriatrics Society.
Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.
Moreira, Afonso; Diógenes, Maria José; de Mendonça, Alexandre; Lunet, Nuno; Barros, Henrique
2016-05-06
Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected. The median follow-up was 48 months. Dietary habits were evaluated at baseline. The MMSE was used to assess global cognitive function at baseline and at follow-up. Cognitive decline was defined by a decrease ≥ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates were adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes. Chocolate intake was associated with a lower risk of cognitive decline (RR = 0.59, 95% CI 0.38-0.92). This protective effect was observed only among subjects with an average daily consumption of caffeine lower than 75 mg (69% of the participants; RR = 0.50, 95% CI 0.31-0.82). To our knowledge, this is the first prospective cohort study to show an inverse association between regular long-term chocolate consumption and cognitive decline in humans.
Mental work demands, retirement, and longitudinal trajectories of cognitive functioning.
Fisher, Gwenith G; Stachowski, Alicia; Infurna, Frank J; Faul, Jessica D; Grosch, James; Tetrick, Lois E
2014-04-01
Age-related changes in cognitive abilities are well-documented, and a very important indicator of health, functioning, and decline in later life. However, less is known about the course of cognitive functioning before and after retirement and specifically whether job characteristics during one's time of employment (i.e., higher vs. lower levels of mental work demands) moderate how cognition changes both before and after the transition to retirement. We used data from n = 4,182 (50% women) individuals in the Health and Retirement Study, a nationally representative panel study in the United States, across an 18 year time span (1992-2010). Data were linked to the O*NET occupation codes to gather information about mental job demands to examine whether job characteristics during one's time of employment moderates level and rate of change in cognitive functioning (episodic memory and mental status) both before and after retirement. Results indicated that working in an occupation characterized by higher levels of mental demands was associated with higher levels of cognitive functioning before retirement, and a slower rate of cognitive decline after retirement. We controlled for a number of important covariates, including socioeconomic (education and income), demographic, and health variables. Our discussion focuses on pathways through which job characteristics may be associated with the course of cognitive functioning in relation to the important transition of retirement. Implications for job design as well as retirement are offered.
Mental Work Demands, Retirement, and Longitudinal Trajectories of Cognitive Functioning
Fisher, Gwenith G.; Stachowski, Alicia; Infurna, Frank J.; Faul, Jessica D.; Grosch, James; Tetrick, Lois E.
2015-01-01
Age-related changes in cognitive abilities are well-documented, and a very important indicator of health, functioning, and decline in later life. However, less is known about the course of cognitive functioning before and after retirement and specifically whether job characteristics during one's time of employment (i.e., higher vs. lower levels of mental work demands) moderate how cognition changes both before and after the transition to retirement. We used data from n = 4,182 (50% women) individuals in the Health and Retirement Study, a nationally representative panel study in the United States, across an 18 year time span (1992–2010). Data were linked to the O'NET occupation codes to gather information about mental job demands to examine whether job characteristics during one's time of employment moderates level and rate of change in cognitive functioning (episodic memory and mental status) both before and after retirement. Results indicated that working in an occupation characterized by higher levels of mental demands was associated with higher levels of cognitive functioning before retirement, and a slower rate of cognitive decline after retirement. We controlled for a number of important covariates, including socioeconomic (education and income), demographic, and health variables. Our discussion focuses on pathways through which job characteristics may be associated with the course of cognitive functioning in relation to the important transition of retirement. Implications for job design as well as retirement are offered. PMID:24635733
Falbo, S.; Condello, G.; Capranica, L.; Forte, R.
2016-01-01
Physical and cognitive training seem to counteract age-related decline in physical and mental function. Recently, the possibility of integrating cognitive demands into physical training has attracted attention. The purpose of this study was to evaluate the effects of twelve weeks of designed physical-cognitive training on executive cognitive function and gait performance in older adults. Thirty-six healthy, active individuals aged 72.30 ± 5.84 years were assigned to two types of physical training with major focus on physical single task (ST) training (n = 16) and physical-cognitive dual task (DT) training (n = 20), respectively. They were tested before and after the intervention for executive function (inhibition, working memory) through Random Number Generation and for gait (walking with/without negotiating hurdles) under both single and dual task (ST, DT) conditions. Gait performance improved in both groups, while inhibitory performance decreased after exercise training with ST focus but tended to increase after training with physical-cognitive DT focus. Changes in inhibition performance were correlated with changes in DT walking performance with group differences as a function of motor task complexity (with/without hurdling). The study supports the effectiveness of group exercise classes for older individuals to improve gait performance, with physical-cognitive DT training selectively counteracting the age-related decline in a core executive function essential for daily living. PMID:28053985
Falbo, S; Condello, G; Capranica, L; Forte, R; Pesce, C
2016-01-01
Physical and cognitive training seem to counteract age-related decline in physical and mental function. Recently, the possibility of integrating cognitive demands into physical training has attracted attention. The purpose of this study was to evaluate the effects of twelve weeks of designed physical-cognitive training on executive cognitive function and gait performance in older adults. Thirty-six healthy, active individuals aged 72.30 ± 5.84 years were assigned to two types of physical training with major focus on physical single task (ST) training ( n = 16) and physical-cognitive dual task (DT) training ( n = 20), respectively. They were tested before and after the intervention for executive function (inhibition, working memory) through Random Number Generation and for gait (walking with/without negotiating hurdles) under both single and dual task (ST, DT) conditions. Gait performance improved in both groups, while inhibitory performance decreased after exercise training with ST focus but tended to increase after training with physical-cognitive DT focus. Changes in inhibition performance were correlated with changes in DT walking performance with group differences as a function of motor task complexity (with/without hurdling). The study supports the effectiveness of group exercise classes for older individuals to improve gait performance, with physical-cognitive DT training selectively counteracting the age-related decline in a core executive function essential for daily living.
Hajek, André; Brettschneider, Christian; Lühmann, Dagmar; Eisele, Marion; Mamone, Silke; Wiese, Birgitt; Weyerer, Siegfried; Werle, Jochen; Pentzek, Michael; Fuchs, Angela; Riedel-Heller, Steffi G; Luck, Tobias; Bickel, Horst; Weeg, Dagmar; Koppara, Alexander; Wagner, Michael; Scherer, Martin; Maier, Wolfgang; König, Hans-Helmut
2016-11-01
To examine how visual impairment affects physical and cognitive function in old age. A longitudinal population-based prospective cohort study. General practitioner offices at six study centers in Germany. They were observed every 1.5 years over four waves. Individuals aged 77-101 at follow-up Wave 2 (N = 2,394). Physical and cognitive function were assessed using an adapted scale that had been previously developed, and visual impairment was rated on a Likert scale (none, mild, severe or profound). Adjusting for sociodemographic factors and comorbidity, linear fixed-effects regression showed that the onset of severe visual impairment was associated with a decline in physical function score in the total sample (β = -0.15, P = .01) and in women (β = -.15, P = .03). Moreover, the onset of severe visual impairment was associated with decline in cognitive function score in the total sample (β = -0.38, P < .001) and in women (β = -0.38, P < .001) and men (β = -0.37, P = .001). Visual impairment affects physical and cognitive function in old age. Interventional strategies to postpone visual impairment may contribute to maintaining physical and cognitive function. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.
The beneficial effects of berry fruit on cognitive and neuronal function in aging
USDA-ARS?s Scientific Manuscript database
Research has demonstrated, in both human and animals, that cognition decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associated changes i...
USDA-ARS?s Scientific Manuscript database
Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...
Hannigan, Caoimhe; Coen, Robert F; Lawlor, Brian A; Robertson, Ian H; Brennan, Sabina
2015-01-01
Population ageing is a global phenomenon that has characterised demographic trends during the 20th and 21st century. The rapid growth in the proportion of older adults in the population, and resultant increase in the incidence of age-related cognitive decline, dementia and Alzheimer's disease, brings significant social, economic and healthcare challenges. Decline in cognitive abilities represents the most profound threat to active and healthy ageing. Current evidence suggests that a significant proportion of cases of age-related cognitive decline and dementia may be preventable through the modification of risk factors including education, depressive symptomology, physical activity, social engagement and participation in cognitively stimulating activities. The NEIL Memory Research Unit cohort study was established to investigate factors related to brain health and the maintenance of cognitive function. A cohort of 1000 normally ageing adults aged 50 years and over are being recruited to participate in comprehensive assessments at baseline, and at follow-up once every 2 years. The assessment protocol comprises a comprehensive neuropsychological battery, some basic physical measures, psychosocial scales, questionnaire measures related to a range of health, lifestyle and behavioural factors, and a measure of resting state activity using electroencephalography (EEG). The NEIL Memory Research Unit cohort study will address key questions about brain health and cognitive ageing in the population aged 50+, with a particular emphasis on the influence of potentially modifiable factors on cognitive outcomes. Analyses will be conducted with a focus on factors involved in the maintenance of cognitive function among older adults, and therefore will have the potential to contribute significant knowledge related to key questions within the field of cognitive ageing, and to inform the development of public health interventions aimed at preventing cognitive decline and promoting active and healthy ageing.
Tucsek, Zsuzsanna; Toth, Peter; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Warrington, Junie P.; Giles, Cory B.; Wren, Jonathan D.; Koller, Akos; Ballabh, Praveen; Sonntag, William E.; Csiszar, Anna
2014-01-01
Epidemiological studies show that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular impairment, we compared young (7 months) and aged (24 months) high-fat diet–fed obese C57BL/6 mice. We found that aging exacerbates the obesity-induced decline in microvascular density both in the hippocampus and in the cortex. The extent of hippocampal microvascular rarefaction and the extent of impairment of hippocampal-dependent cognitive function positively correlate. Aging exacerbates obesity-induced loss of pericyte coverage on cerebral microvessels and alters hippocampal angiogenic gene expression signature, which likely contributes to microvascular rarefaction. Aging also exacerbates obesity-induced oxidative stress and induction of NADPH oxidase and impairs cerebral blood flow responses to whisker stimulation. Collectively, obesity exerts deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular rarefaction and neurovascular uncoupling. The morphological and functional impairment of the cerebral microvasculature in association with increased blood–brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et al. Obesity in aging exacerbates blood–brain barrier disruption, neuroinflammation and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to obesity-induced cognitive decline in aging. PMID:24895269
Hess, Thomas M.
2018-01-01
In this article, I present a framework for understanding the impact of aging-related declines in cognitive resources on functioning. I make the assumption that aging is associated with an increase in the costs of cognitive engagement, as reflected in both the effort required to achieve a specific level of task performance and the associated depletion or fatigue effects. I further argue that these costs result in older adults being increasingly selective in the engagement of cognitive resources in response to these declines. This selectivity is reflected in (a) a reduction in the intrinsic motivation to engage in cognitively demanding activities, which, in part, accounts for general reductions in engagement in such activities, and (b) greater sensitivity to the self-related implications of a given task. Both processes are adaptive if viewed in terms of resource conservation, but the former may also be maladaptive to the extent that it results in older adults restricting participation in cognitively demanding activities that could ultimately benefit cognitive health. I review supportive research and make the general case for the importance of considering motivational factors in understanding aging effects on cognitive functioning. PMID:26173272
Fibrillar amyloid correlates of preclinical cognitive decline.
Stonnington, Cynthia M; Chen, Kewei; Lee, Wendy; Locke, Dona E C; Dueck, Amylou C; Liu, Xiaofen; Roontiva, Auttawut; Fleisher, Adam S; Caselli, Richard J; Reiman, Eric M
2014-01-01
It is not known whether preclinical cognitive decline is associated with fibrillar β-amyloid (Aβ) deposition irrespective of apolipoprotein E (APOE) ε4 status. From a prospective observational study of 623 cognitively normal individuals, we identified all subjects who showed preclinical decline of at least 2 standard deviations beyond the decline of the entire group in memory or executive function. Fourteen decliners were matched by APOE ε4 gene dose, age, sex, and education with 14 nondecliners. Dynamic Pittsburgh compound B (PiB) positron emission tomography (PET) scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest were used to characterize and compare cerebral-to-cerebellar PiB distribution volume ratios (DVRs), reflecting fibrillar Aβ burden. At P < .005 (uncorrected), decliners had significantly greater DVRs in comparison to nondecliners. Asymptomatic longitudinal neuropsychological decline is associated with subsequent increased fibrillar amyloid deposition, even when controlling for APOE ε4 genotype. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Obermeit, Lisa C.; Beltran, Jessica; Casaletto, Kaitlin B.; Franklin, Donald R.; Letendre, Scott; Ellis, Ronald; Fennema-Notestine, Christine; Vaida, Florin; Collier, Ann C.; Marra, Christina M.; Clifford, David; Gelman, Benjamin; Sacktor, Ned; Morgello, Susan; Simpson, David; McCutchan, J. Allen; Grant, Igor
2016-01-01
The criteria for differentiating symptomatic from asymptomatic HIV-associated neurocognitive disorder require evaluation of (1) cognitive impairment, (2) daily functioning declines, and (3) whether the functional declines are attributable to cognitive versus physical problems. Many providers rely only on self-report to evaluate these latter criteria. However, the accuracy of patient-provided information may be limited. This study evaluated the validity of self-assessment for HIV-associated neurocognitive disorder (HAND) diagnoses by comparing objective findings with self-report of criteria 2 and 3 above. Self-reports were used to stratify 277 cognitively impaired HIV+ individuals into functionally dependent (n = 159) and independent (n = 118) groups, followed by group comparisons of objective functional problems. The dependent group was then divided into those who self-attributed their functional dependence to only cognitive (n = 80) versus only physical (n = 79) causes, for further comparisons on objective findings. The functionally dependent group was significantly worse than the independent group on all objective disability characteristics except severity of cognitive impairment, while those who attributed their dependence to physical (versus cognitive) factors were similar on all objective physical, cognitive, and functioning variables. Of note, 28 % of physical attributors showed no physical abnormalities on neuromedical examinations. Results suggest that patient report is consistently associated with objective measures of functional loss; in contrast, patient identification of physical versus cognitive causes is poorly associated with objective criteria. These findings caution against relying solely on patient self-report to determine whether functional disability in cognitively impaired HIV+ individuals can be attributed to strictly physical causes. PMID:27557777
Engeroff, Tobias; Ingmann, Tobias; Banzer, Winfried
2018-06-01
A growing body of literature suggests that physical activity might alleviate the age-related neurodegeneration and decline of cognitive function. However, most of this evidence is based on data investigating the association of exercise interventions or current physical activity behavior with cognitive function in elderly subjects. We performed a systematic review and hypothesize that physical activity during the adult life span is connected with maintained domain-specific cognitive functions during late adulthood defined as age 60+ years. We performed a systematic literature search up to November 2017 in PubMed, Web of Science, and Google Scholar without language limitations for studies analyzing the association of leisure physical activity during the adult life span (age 18+ years) and domain-specific cognitive functions in older adults (age 60+ years). The literature review yielded 14,294 articles and after applying inclusion and exclusion criteria, nine cross-sectional and 14 longitudinal studies were included. Moderate- and vigorous-intensity leisure physical activity was associated with global cognitive function and specific cognitive domains including executive functions and memory but not attention or working memory. Most studies assessed mid- to late-adulthood physical activity, thus information concerning the influence of young adult life-span physical activity is currently lacking. Observational evidence that moderate- and vigorous-intensity leisure physical activity is beneficially associated with maintained cognitive functions during old age is accumulating. Further studies are necessary to confirm a causal link by assessing objective physical activity data and the decline of cognitive functions at multiple time points during old age.
ERIC Educational Resources Information Center
Labelle, Veronique; Bosquet, Laurent; Mekary, Said; Bherer, Louis
2013-01-01
Studies on the effects of acute bouts of cardiovascular exercise on cognitive performances show contradictory findings due to methodological differences (e.g., exercise intensity, cognitive function assessed, participants' aerobic fitness level, etc.). The present study assessed the acute effect of exercise intensity on cognition while controlling…
Cerebroprotective effect of piracetam in patients undergoing open heart surgery.
Holinski, Sebastian; Claus, Benjamin; Alaaraj, Nour; Dohmen, Pascal Maria; Neumann, Konrad; Uebelhack, Ralf; Konertz, Wolfgang
2011-01-01
Reduction of cognitive function is a possible side effect after the use of cardiopulmonary bypass (CPB) during cardiac surgery. Since it has been proven that piracetam is cerebroprotective in patients undergoing coronary bypass surgery, we investigated the effects of piracetam on the cognitive performance of patients undergoing open heart surgery. Patients scheduled for elective open heart surgery were randomized to the piracetam or placebo group in a double-blind study. Patients received 12 g of piracetam or placebo at the beginning of the operation. Six neuropsychological subtests from the Syndrom Kurz Test and the Alzheimer's Disease Assessment Scale were performed preoperatively and on day 3, postoperatively. To assess the overall cognitive function and the degree of cognitive decline across all tests after the surgery, we combined the six test-scores by principal component analysis. A total of 88 patients with a mean age of 67 years were enrolled into the study. The mean duration of CPB was 110 minutes. Preoperative clinical parameters and overall cognitive functions were not significantly different between the groups. The postoperative combined score of the neuropsychological tests showed deterioration of cognitive function in both groups (piracetam: preoperative 0.19 ± 0.97 vs. postoperative -0.97 ± 1.38, p <0.0005 and placebo: preoperative -0.14 ± 0.98 vs. postoperative -1.35 ± 1.23, p <0.0005). Patients taking piracetam did not perform better than those taking placebo, and both groups had the same decline of overall cognitive function (p = 0.955). Piracetam had no cerebroprotective effect in patients undergoing open heart surgery. Unlike the patients who underwent coronary surgery, piracetam did not reduce the early postoperative decline of neuropsychological abilities in heart valve patients.
Tian, Qu; An, Yang; Resnick, Susan M; Studenski, Stephanie
2017-05-01
most older individuals who experience mobility decline, also show cognitive decline, but whether cognitive decline precedes or follows mobility limitation is not well understood. examine the temporal sequence of mobility and cognition among initially unimpaired older adults. mobility and cognition were assessed every 2 years for 6 years in 412 participants aged ≥60 with initially unimpaired cognition and gait speed. Using autoregressive models, accounting for the dependent variable from the prior assessment, baseline age, sex, body mass index and education, we examine the temporal sequence of change in mobility (6 m usual gait speed, 400 m fast walk time) and executive function (visuoperceptual speed: Digit Symbol Substitution Test (DSST); cognitive flexibility: Trail Making Test part B (TMT-B)) or memory (California Verbal Learning Test (CVLT) immediate, short-delay, long-delay). there was a bidirectional relationship over time between slower usual gait speed and both poorer DSST and TMT-B scores (Bonferroni-corrected P < 0.005). In contrast, slower 400 m fast walk time predicted subsequent poorer DSST, TMT-B, CVLT immediate recall and CVLT short-delay scores (P < 0.005), while these measures did not predict subsequent 400 m fast walk time (P > 0.005). among initially unimpaired older adults, the temporal relationship between usual gait speed and executive function is bidirectional, with each predicting change in the other, while poor fast walking performance predicts future executive function and memory changes but not vice versa. Challenging tasks like the 400 m walk appear superior to usual gait speed for predicting executive function and memory change in unimpaired older adults. Published by Oxford University Press on behalf of the British Geriatrics Society 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Real-Time fMRI in Neuroscience Research and Its Use in Studying the Aging Brain
Rana, Mohit; Varan, Andrew Q.; Davoudi, Anis; Cohen, Ronald A.; Sitaram, Ranganatha; Ebner, Natalie C.
2016-01-01
Cognitive decline is a major concern in the aging population. It is normative to experience some deterioration in cognitive abilities with advanced age such as related to memory performance, attention distraction to interference, task switching, and processing speed. However, intact cognitive functioning in old age is important for leading an independent day-to-day life. Thus, studying ways to counteract or delay the onset of cognitive decline in aging is crucial. The literature offers various explanations for the decline in cognitive performance in aging; among those are age-related gray and white matter atrophy, synaptic degeneration, blood flow reduction, neurochemical alterations, and change in connectivity patterns with advanced age. An emerging literature on neurofeedback and Brain Computer Interface (BCI) reports exciting results supporting the benefits of volitional modulation of brain activity on cognition and behavior. Neurofeedback studies based on real-time functional magnetic resonance imaging (rtfMRI) have shown behavioral changes in schizophrenia and behavioral benefits in nicotine addiction. This article integrates research on cognitive and brain aging with evidence of brain and behavioral modification due to rtfMRI neurofeedback. We offer a state-of-the-art description of the rtfMRI technique with an eye towards its application in aging. We present preliminary results of a feasibility study exploring the possibility of using rtfMRI to train older adults to volitionally control brain activity. Based on these first findings, we discuss possible implementations of rtfMRI neurofeedback as a novel technique to study and alleviate cognitive decline in healthy and pathological aging. PMID:27803662
Solfrizzi, Vincenzo; Custodero, Carlo; Lozupone, Madia; Imbimbo, Bruno P; Valiani, Vincenzo; Agosti, Pasquale; Schilardi, Andrea; D'Introno, Alessia; La Montagna, Maddalena; Calvani, Mariapaola; Guerra, Vito; Sardone, Rodolfo; Abbrescia, Daniela I; Bellomo, Antonello; Greco, Antonio; Daniele, Antonio; Seripa, Davide; Logroscino, Giancarlo; Sabbá, Carlo; Panza, Francesco
2017-01-01
In the last decade, the association between diet and cognitive function or dementia has been largely investigated. In the present article, we systematically reviewed observational studies published in the last three years (2014-2016) on the relationship among dietary factors and late-life cognitive disorders at different levels of investigation (i.e., dietary patterns, foods and food-groups, and dietary micro- and macronutrients), and possible underlying mechanisms of the proposed associations. From the reviewed evidence, the National Institute on Aging-Alzheimer's Association guidelines for Alzheimer's disease (AD) and cognitive decline due to AD pathology introduced some evidence suggesting a direct relation between diet and changes in the brain structure and activity. There was also accumulating evidence that combinations of foods and nutrients into certain patterns may act synergistically to provide stronger health effects than those conferred by their individual dietary components. In particular, higher adherence to a Mediterranean-type diet was associated with decreased cognitive decline. Moreover, also other emerging healthy dietary patterns such as the Dietary Approach to Stop Hypertension (DASH) and the Mediterranean-DASH diet Intervention for Neurodegenerative Delay (MIND) diets were associated with slower rates of cognitive decline and significant reduction of AD rate. Furthermore, some foods or food groups traditionally considered harmful such as eggs and red meat have been partially rehabilitated, while there is still a negative correlation of cognitive functions with saturated fatty acids and a protective effect against cognitive decline of elevated fish consumption, high intake of monounsaturated fatty acids and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA.
Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Segawa, Eisuke; Buchman, Aron S.; Bennett, David A.
2013-01-01
Literacy is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory), and b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. 645 community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those assessed in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n=447) persons with repeated cognitive assessments available for up to 14 years, regression analysis supported the association of multiple resources with literacy; moreover, more rapid declines in executive function and episodic memory over an average of 6.4 years prior to the literacy assessment predicted lower literacy scores (p’s<0.02), but rate of decline in word knowledge did not. These findings suggest that diverse individual resources contribute to financial and health literacy and lower literacy in old age is partially due to declines in executive function and episodic memory. PMID:23957225
Boyle, Patricia A; Yu, Lei; Wilson, Robert S; Segawa, Eisuke; Buchman, Aron S; Bennett, David A
2013-09-01
Literacy is an important determinant of health and well-being across the life span but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: (a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory); and (b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. Six-hundred and forty-five community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those used in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n = 447) persons with repeated cognitive assessments available for up to 14 years, regression analysis supported the association of multiple resources with literacy; moreover, more rapid declines in executive function and episodic memory over an average of 6.4 years prior to the literacy assessment predicted lower literacy scores (ps < 0.02), but rate of decline in word knowledge did not. These findings suggest that diverse individual resources contribute to financial and health literacy and lower literacy in old age is partially due to declines in executive function and episodic memory.
Arab, Lenore; Khan, Faraz; Lam, Helen
2013-01-01
A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men. PMID:23319129
Arab, Lenore; Khan, Faraz; Lam, Helen
2013-01-01
A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men.
Beglinger, Leigh J; Duff, Kevin; Allison, Jessica; Theriault, Danielle; O'Rourke, Justin J F; Leserman, Anne; Paulsen, Jane S
2010-07-01
Huntington disease (HD) is a neurodegenerative disease associated with cognitive, motor, and psychiatric deterioration over time. Although there is currently no cure for HD, there has been a surge of clinical trials available to patients with HD over the past 5 years. However, cognitive measures have generally been lacking from these trials. A brief, repeatable neuropsychological battery is needed to assess cognitive endpoints. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may be useful for assessing change in interventional studies or for clinical monitoring. A total of 38 patients with HD were assessed using the RBANS, other cognitive tests, and the standardized HD battery (Unified Huntington's Disease Rating Scale, UHDRS) at two clinic visits approximately 16 months apart. The RBANS Attention Index, as well as individual subtest scores on Coding, Digit Span, List Recognition, Figure Copy, and Figure Recall all declined significantly over this interval. Performance on the UHDRS cognitive tests (Symbol Digit Modalities; Stroop Color, and Stroop Word) also declined, as did functional capacity. Results suggest that cognitive changes were detected both on established cognitive tasks used in HD research and on the RBANS in patients with measurable functional decline. The RBANS provided additional information about other cognitive domains affected (e.g., memory) and may be a useful measure for tracking longitudinal change.
Postoperative cognitive changes after total knee arthroplasty under regional anesthesia
Jeon, Young-Tae; Kim, Byung-Gun; Park, Young Ho; Sohn, Hye-Min; Kim, Jungeun; Kim, Seung Chan; An, Seong Soo; Kim, SangYun
2016-01-01
Abstract Background: The type of postoperative cognitive decline after surgery under spinal anesthesia is unknown. We investigated the type of postoperative cognitive decline after total knee arthroplasty (TKA). Neuropsychological testing was conducted and the changes in cerebrospinal fluid (CSF) biomarkers after surgery were evaluated. Methods: Fifteen patients who required bilateral TKA at a 1-week interval under spinal anesthesia were included. Neuropsychological tests were performed twice, once the day before the first operation and just before the second operation (usually 1 week after the first test) to determine cognitive decline. Validated neuropsychological tests were used to examine 4 types of cognitive decline: memory, frontal-executive, language-semantic, and others. Concentrations of CSF amyloid peptide, tau protein, and S100B were measured twice during spinal anesthesia at a 1-week interval. The patients showed poor performance in frontal-executive function (forward digit span, semantic fluency, letter-phonemic fluency, and Stroop color reading) at the second compared to the first neuropsychological assessment. Results: S100B concentration decreased significantly 1 week after the operation compared to the basal value (638 ± 178 vs 509 ± 167 pg/mL) (P = 0.019). Amyloid protein β1–42, total tau, and phosphorylated tau concentrations tended to decrease but the changes were not significant. Conclusion: Our results suggest that frontal-executive function declined 1 week after TKA under spinal anesthesia. The CSF biomarker analysis indicated that TKA under regional anesthesia might not cause neuronal damage. PMID:28033253
Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta
2017-01-01
Background: This pilot study investigated the effects of partial pulmonary lobectomy lung surgery on cognitive functions of elderly Japanese patients. It is recognized that elderly patients undergoing surgery have increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery is aging. Methods: Cognitive function was measured for all subjects ( n = 12) before and after surgery using three different cognitive tests: Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), and a computerized Cogstate Brief Battery (CBB). Changes in these measures indicate changes in cognitive function. In addition, the 12-item General Health Questionnaire (GHQ-12), the Geriatric Depression Scale (GDS), and the 5-item Quality of Life questionnaire (QOL-5) were administered at each time point to measure mental and emotional state. Changes in outcome measures were analyzed via Wilcoxon signed-rank test. Exploratory correlation analysis was conducted using Spearman's rho. Results: Data show a decline in detection (DET; p = 0.045) and identification (IDN; p = 0.038). Spearman's correlation coefficient show a significant correlation between postoperative DET scores and postoperative IDN scores (ρ = 0.78, p = 0.005), a significant correlation between change in IDN and baseline GHQ-12 scores (ρ = -0.595, p = 0.027), and a significant correlation between change in one-back (OBK) scores and duration of anesthesia (ρ = -0.72, p = 0.012). Discussion: This was the first report to examine cognitive decline after major thoracic surgery in Japanese patients. Previous studies have evidenced that POCD is a common phenomenon after surgery, and that age is a major risk factor. The CCB measured significant change in two cognitive domains: attention and psycomotor function. This study clarified that decline in cognition is detectable in certain measures after thoracic surgery in the elderly Japanese patient population. Additionally, longer anesthetic exposure may negatively impact attention and working memory, and preoperative mental wellbeing is a possible predictor of POCD. These preliminary results have important implications and support the need for future studies.
Mandelblatt, Jeanne S; Clapp, Jonathan D; Luta, Gheorghe; Faul, Leigh Anne; Tallarico, Michelle D; McClendon, Trina D; Whitley, Jessica A; Cai, Ling; Ahles, Tim A; Stern, Robert A; Jacobsen, Paul B; Small, Brent J; Pitcher, Brandelyn N; Dura-Fernandis, Estrella; Muss, Hyman B; Hurria, Arti; Cohen, Harvey J; Isaacs, Claudine
2016-07-22
The number of survivors of breast cancer aged ≥65 years ("older") is growing, but to the authors' knowledge, little is known regarding the cognitive outcomes of these individuals. A cohort of cognitively intact older survivors with nonmetastatic, invasive breast cancer was recruited from 78 sites from 2004 through 2011; approximately 83.7% of the survivors (1280 survivors) completed baseline assessments. Follow-up data were collected at 6 months and annually for up to 7 years (median, 4.1 years). Cognitive function was self-reported using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30); scores ranged from 0 to 100, with a higher score indicating better function. Group-based trajectory modeling determined trajectories; women were assigned to a trajectory group based on the highest predicted probability of membership. Multinomial logistic regression evaluated the association between receipt of chemotherapy (with or without hormonal treatment) and trajectory group. Survivors were aged 65 to 91 years; approximately 41% received chemotherapy. There were 3 cognitive trajectories: "maintained high" (42.3% of survivors); "phase shift" (50.1% of survivors), with scores slightly below but parallel to maintained high; and "accelerated decline" (7.6% of survivors), with the lowest baseline scores and greatest decline (from 71.7 [standard deviation, 19.8] to 58.3 [standard deviation, 21.9]). The adjusted odds of being in the accelerated decline group (vs the maintained high group) were 2.1 times higher (95% confidence interval, 1.3-3.5) for survivors who received chemotherapy (with or without hormonal therapy) versus those treated with hormonal therapy alone. Greater comorbidity and frailty also were found to be associated with accelerated decline. Trajectory group analysis demonstrated that the majority of older survivors maintained good long-term self-reported cognitive function, and that only a small subset who were exposed to chemotherapy manifested accelerated cognitive decline. Future research is needed to determine factors that place some older survivors at risk of experiencing cognitive decline. Cancer 2016. 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Luo, Jia; Wang, Tao; Liang, Shan; Hu, Xu; Li, Wei; Jin, Feng
2014-03-01
Evidence suggests that the hyperammonemia (HA)-induced neuroinflammation and alterations in the serotonin (5-HT) system may contribute to cognitive decline and anxiety disorder during hepatic encephalopathy (HE). Probiotics that maintain immune system homeostasis and regulate the 5-HT system may be potential treatment for HA-mediated neurological disorders in HE. In this study, we tested the efficacy of probiotic Lactobacillus helveticus strain NS8 in preventing cognitive decline and anxiety-like behavior in HA rats. Chronic HA was induced by intraperitoneal injection of ammonium acetate for four weeks in male Sprague-Dawley rats. HA rats were then given Lactobacillus helveticus strain NS8 (10(9) CFU mL(-1)) in drinking water as a daily supplementation. The Morris water maze task assessed cognitive function, and the elevated plus maze test evaluated anxiety-like behavior. Neuroinflammation was assessed by measuring the inflammatory markers: inducible nitric oxide synthase, prostaglandin E2, and interleukin-1 β in the brain. 5-HT system activity was evaluated by measuring 5-HT and its metabolite, 5-HIAA, and the 5-HT precursor, tryptophan. Probiotic treatment of HA rats significantly reduced the level of inflammatory markers, decreased 5-HT metabolism, restored cognitive function and improved anxiety-like behavior. These results indicate that probiotic L. helveticus strain NS8 is beneficial for the treatment of cognitive decline and anxiety-like behavior in HA rats.
Cerebral microbleeds are associated with cognitive decline and dementia: the Rotterdam Study
Akoudad, Saloua; Wolters, Frank J.; Viswanathan, Anand; de Bruijn, Renée F.; van der Lugt, Aad; Hofman, Albert; Koudstaal, Peter J.; Ikram, M. Arfan; Vernooij, Meike W.
2018-01-01
Importance Cerebral microbleeds are hypothesized downstream markers of brain damage caused by both vascular and amyloid pathological mechanisms. To date, it remains unclear whether their presence if associated with cognitive deterioration in the general population. Objective To determine whether microbleeds, and more specifically microbleed count and location, associate with an increased risk of cognitive impairment and dementia in the general population. Design Prospective population-based Rotterdam Study. Setting General community. Participants In the Rotterdam Study, we assessed presence, number, and location of microbleeds at baseline (2005–2011) on brain MRI of 4,841 participants aged ≥45 years. Participants underwent neuropsychological testing at two time points on average 5.9 years (SD 0.6) apart, and were followed for incident dementia throughout the study period until 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed effects modeling, and Cox proportional hazards. Exposure cerebral microbleed presence, location, and number. Main outcomes cognitive decline and dementia. Results Microbleed prevalence was 15.3% (median count 1 [1–88]). Presence of >4 microbleeds associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with decline in executive functions, information processing, and memory function, whereas microbleeds in other brain regions were associated with decline in information processing and motor speed. After mean follow-up of 4.8 years (SD 1.4), 72 people developed dementia, of whom 53 had Alzheimer’s disease. Presence of microbleeds was associated with an increased risk of dementia (age, sex, education adjusted HR 2.02, 95%CI 1.25;3.24), including Alzheimer’s dementia (HR 2.10, 95%CI 1.21;3.64). Conclusions and relevance In the general population, a high microbleed count associated with an increased risk of cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage. PMID:27271785
The level of cognitive function and recognition of emotions in older adults
Singh-Manoux, Archana; Batty, G. David; Ebmeier, Klaus P.; Jokela, Markus; Harmer, Catherine J.; Kivimäki, Mika
2017-01-01
Background The association between cognitive decline and the ability to recognise emotions in interpersonal communication is not well understood. We aimed to investigate the association between cognitive function and the ability to recognise emotions in other people’s facial expressions across the full continuum of cognitive capacity. Methods Cross-sectional analysis of 4039 participants (3016 men, 1023 women aged 59 to 82 years) in the Whitehall II study. Cognitive function was assessed using a 30-item Mini-Mental State Examination (MMSE), further classified into 8 groups: 30, 29, 28, 27, 26, 25, 24, and <24 (possible dementia) MMSE points. The Facial Expression Recognition Task (FERT) was used to examine recognition of anger, fear, disgust, sadness, and happiness. Results The multivariable adjusted difference in the percentage of accurate recognition between the highest and lowest MMSE group was 14.9 (95%CI, 11.1–18.7) for anger, 15.5 (11.9–19.2) for fear, 18.5 (15.2–21.8) for disgust, 11.6 (7.3–16.0) for sadness, and 6.3 (3.1–9.4) for happiness. However, recognition of several emotions was reduced already after 1 to 2-point reduction in MMSE and with further points down in MMSE, the recognition worsened at an accelerated rate. Conclusions The ability to recognize emotion in facial expressions is affected at an early stage of cognitive impairment and might decline at an accelerated rate with the deterioration of cognitive function. Accurate recognition of happiness seems to be less affected by a severe decline in cognitive performance than recognition of negatively valued emotions. PMID:28977015
Feasibility of a cognitive strategy training intervention for people with Parkinson's disease.
Foster, Erin R; Spence, Daniel; Toglia, Joan
2018-05-01
To investigate the feasibility of a novel client-centered cognitive strategy training intervention for people with Parkinson's disease (PD). This was a case series of seven people with PD without dementia but with subjective cognitive decline. The intervention involved ≥5 treatment sessions at the participant's home. Participant acceptance and engagement were assessed by the Credibility/Expectancy Questionnaire (CEQ), Client Satisfaction Questionnaire (CSQ), enjoyment and effort ratings, and homework completion. Logistical information was tracked, and the Canadian Occupational Performance Measure (COPM) was an exploratory outcome measure. Data analysis was descriptive. CEQ scores were positive and increased over time. CSQ scores were high (M = 30.8, SD = 0.75), with all participants rating all items positively. Almost all (95%) effort and enjoyment ratings were ≥3 (Much), and homework completion rates averaged 84% (SD = 18). Intervention duration was 6-15 weeks (M = 9.2, SD = 2.8), with treatment sessions averaging 1.7 h (SD = 0.5). Group and most individual COPM ratings improved ≥2 points. These findings support the feasibility of the intervention for people with PD. It was acceptable, engaging, and promising in terms of its effect on self-identified functional cognitive problems. Implications for Rehabilitation People with Parkinson's disease (PD) without dementia can experience cognitive decline that negatively impacts function and quality of life. Strategy-based interventions that explicitly train for transfer may mitigate the negative functional consequences of cognitive decline in this population. We developed a client-centered cognitive strategy training intervention for people with PD. This small case series supports its feasibility, indicating that it is acceptable and engaging for people with PD and promising in terms of its effect on self-identified functional cognitive problems.
Antioxidant intake and cognitive function of elderly men and women: the Cache County Study.
Wengreen, H J; Munger, R G; Corcoran, C D; Zandi, P; Hayden, K M; Fotuhi, M; Skoog, I; Norton, M C; Tschanz, J; Breitner, J C S; Welsh-Bohmer, K A
2007-01-01
We prospectively examined associations between intakes of antioxidants (vitamins C, vitamin E, and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah. In 1995, 3831 residents 65 years of age or older completed a baseline survey that included a food frequency questionnaire and cognitive assessment. Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and at three subsequent follow-up interviews spanning approximately 7 years. Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time. Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for food sources compared to supplement or food and supplement sources combined. Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake. High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly.
Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline
ERIC Educational Resources Information Center
Pakhomov, Serguei V. S.; Hemmy, Laura S.; Lim, Kelvin O.
2012-01-01
The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer's disease and mild cognitive impairment are…
van der Ploeg, Eva S; Hoorweg, Angela; van der Lee, Jacqueline
2016-04-01
Cognitive impairment associated with dementia is characterized by a continuous decline. Cognitive training is a method to train specific brain functions such as memory and attention to prevent or slow down cognitive decline. A small number of studies has shown that cognitive training on a computer has a positive effect on both cognition and mood in people with cognitive impairment. This pilot study tested if serious games could be integrated in a psychogeriatric rehabilitation center. Fourteen psychogeriatric patients participated twice weekly in cognitive training sessions on a computer. Both the participants and the facilitator reported positive interactions and outcomes. However, after five weeks only half of the sample still participated in the training. This was partly because of patient turn-over as well as incorporating this new task in the facilitators' daily work. Fear of failure, physical limitations and rapidly decreasing cognitive function led to drop out according to the facilitator. The engagement of patients in the games and the role of the facilitator seemed essential for success, especially monitoring (and adjusting) the difficulty level of the program for every individual participant.
Harada, Kazuhiro; Lee, Sangyoon; Park, Hyuntae; Shimada, Hiroyuki; Makizako, Hyuma; Doi, Takehiko; Yoshida, Daisuke; Tsutsumimoto, Kota; Anan, Yuya; Uemura, Kazuki; Suzuki, Takao
2016-01-01
Identifying the risk factors of cognitive impairment is essential for implementing effective prevention strategies for dementia. Previous studies have shown that the frequency of going outdoors is inversely associated with cognitive decline. Little research has examined whether the relationship between going outdoors and cognitive decline varies with physical functioning in older adults. The aim of the present study was to examine the relationship between going outdoors and cognitive function in older adults with and without physical function limitations. The present study analyzed the data of 4450 individuals (aged 65 years or older) who participated in the Obu Study of Health Promotion for the Elderly. The measures were the Mini-Mental State Examination (MMSE), going outdoors (at least once a week or not), self-reported physical function limitations (with or without), and demographic and health-related factors as potential confounders. Analysis of covariance and post-hoc comparisons showed that although going outdoors at least once a week was associated with higher MMSE scores among older adults with limited physical function, it was not significantly associated with the MMSE scores among older adults without limited physical function. Similarly, logistic regression analyses, stratified by physical function, showed a significant association between going outdoors and MMSE (<24 points or not) among older adults with limited physical function. The results show that going outdoors less than once a week is associated with decreased cognitive function among older adults with limited physical function, but it is not associated with cognitive function among older adults without limited physical function. © 2015 Japan Geriatrics Society.
Age as a Predictor of Cognitive Decline in Bipolar Disorder
Lewandowski, Kathryn E.; Sperry, Sarah H.; Malloy, Mary C.; Forester, Brent P.
2013-01-01
Objective Cognitive dysfunction is a core feature of Bipolar Disorder (BD) in both adult and geriatric patients. However, little is known about whether cognitive functioning declines at a faster rate in patients with BD and there are conflicting reports regarding the relationship between age and cognitive functioning in this population. This cross-sectional study examined the relationship between age and cognitive functioning in patients with BD. Methods Patients with BD I (n=113) and healthy adults (n=64) ages 18–87 completed measures of processing speed, attention, executive functioning, verbal fluency, and clinical symptomatology. Groupwise comparisons were used to examine differences between patients and the comparison group and adult and geriatric BD cohorts. A series of linear regressions was conducted to examine the relationship of age and cognitive functioning, and clinical variables and cognition. Results Patients performed significantly worse than the comparison group on all neuropsychological measures. Age was a significant predictor of Trails A scores with older age associated with worse performance. Conclusions Older age was associated with poorer performance on Trails A in patients with BD but not healthy adults. These results are suggestive of greater dysfunction in processing speed with older age in patients with BD compared to a healthy comparison group. As cognitive functioning is associated with community outcomes, these findings suggest a need for treatments targeting cognitive symptoms across the lifespan. Future research exploring neurobiological evidence for neurodegenerative processes in bipolar disorder will pave the way for potential therapeutic interventions. PMID:24262287
APOE epsilon 4 allele predicts faster cognitive decline in mild Alzheimer disease.
Cosentino, S; Scarmeas, N; Helzner, E; Glymour, M M; Brandt, J; Albert, M; Blacker, D; Stern, Y
2008-05-06
To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample. The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.
Scuteri, Angelo; Tesauro, Manfredi; Guglini, Letizia; Lauro, Davide; Fini, Massimo; Di Daniele, Nicola
2013-11-20
Though CV risk factors and markers of arterial aging are recognized risky for cognition, no study has simultaneously investigated the impact of multiple cardiac, arterial (large and small vessels), and hemodynamic parameters on cognitive function in older subjects. Two hundred eighty older subjects with subjective complaints of memory loss and no previous stroke (mean age 78.3 ± 6.3 years) were studied. Global cognitive function was evaluated with the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a MMSE < 21. We measured: traditional CV risk factors; aorta stiffness (Pulse Wave Velocity, PWV); LV mass; presence of WML at neuroimaging; episodes of hypotension (SBP <100 mmHg during 24 h Ambulatory Blood Pressure Monitoring). In both cross-sectional and longitudinal analyses PWV, WML, and episodes of hypotension were significantly associated with poorer cognitive function-controlling for age, sex, education, depression, traditional CV risk factors, and medications. LV mass was no longer associated with cognition in multiple regression. Older subjects with stiffer arteries or episodes of hypotension presented a 4-fold and an 11-fold, respectively, greater odds for progression from normal cognitive function to cognitive impairment. A synergistic effect between PWV, WML, and hypotension was observed: the occurrence of any two of PWV, WML, or hypotension was accompanied by lower MMSE; in the presence of all three factors, a further significant decline in cognitive function was observed. Systemic hemodynamic parameters (higher PWV and hypotension) together with cerebral microvascular damage (WML) are significantly associated with poorer cognitive function and may identify older subjects with subjective complaints of memory loss at higher risk of cognitive decline. © 2013.
Mandelblatt, Jeanne S; Hurria, Arti; McDonald, Brenna C; Saykin, Andrew J; Stern, Robert A; VanMeter, John W; McGuckin, Meghan; Traina, Tiffani; Denduluri, Neelima; Turner, Scott; Howard, Darlene; Jacobsen, Paul B; Ahles, Tim
2013-12-01
There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included subjects aged 65 years and older, it is logical to expect that older patients are at risk of cognitive decline. Here, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There also are similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with "normal" aging and Alzheimer's disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors, and frailty phenotypes to best identify the subgroups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients. © 2013 Elsevier Inc. All rights reserved.
Mandelblatt, Jeanne S.; Hurria, Arti; McDonald, Brenna C.; Saykin, Andrew J.; Stern, Robert A.; VanMeter, John W.; McGuckin, Meghan; Traina, Tiffani; Denduluri, Neelima; Turner, Scott; Howard, Darlene; Jacobsen, Paul B.; Ahles, Tim
2013-01-01
There is a fairly consistent, albeit non-universal body of research documenting cognitive declines after cancer and its treatments. While few of these studies have included those 65 and older, it is logical to expect that older patients are at risk of cognitive decline. In this paper, we use breast cancer as an exemplar disease for inquiry into the intersection of aging and cognitive effects of cancer and its therapies. There are a striking number of common underlying potential biological risks and pathways for the development of cancer, cancer-related cognitive declines, and aging processes, including the development of a frail phenotype. Candidate shared pathways include changes in hormonal milieu, inflammation, oxidative stress, DNA damage and compromised DNA repair, genetic susceptibility, decreased brain blood flow or disruption of the blood-brain barrier, direct neurotoxicity, decreased telomere length, and cell senescence. There are also similar structure and functional changes seen in brain imaging studies of cancer patients and those seen with “normal” aging and Alzheimer’s disease. Disentangling the role of these overlapping processes is difficult since they require aged animal models and large samples of older human subjects. From what we do know, frailty and its low cognitive reserve seem to be a clinically useful marker of risk for cognitive decline after cancer and its treatments. This and other results from this review suggest the value of geriatric assessments to identify older patients at the highest risk of cognitive decline. Further research is needed to understand the interactions between aging, genetic predisposition, lifestyle factors and frailty phenotypes to best identify the sub-groups of older patients at greatest risk for decline and to develop behavioral and pharmacological interventions targeting this group. We recommend that basic science and population trials be developed specifically for older hosts with intermediate endpoints of relevance to this group, including cognitive function and trajectories of frailty. Clinicians and their older patients can advance the field by active encouragement of and participation in research designed to improve the care and outcomes of the growing population of older cancer patients. PMID:24331192
Executive dysfunction, brain aging, and political leadership.
Fisher, Mark; Franklin, David L; Post, Jerrold M
2014-01-01
Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.
Apathy and Reduced Speed of Processing Underlie Decline in Verbal Fluency following DBS
Foltynie, Tom; Zrinzo, Ludvic; Hyam, Jonathan A.; Limousin, Patricia
2017-01-01
Objective. Reduced verbal fluency is a strikingly uniform finding following deep brain stimulation (DBS) for Parkinson's disease (PD). The precise cognitive mechanism underlying this reduction remains unclear, but theories have suggested reduced motivation, linguistic skill, and/or executive function. It is of note, however, that previous reports have failed to consider the potential role of any changes in speed of processing. Thus, the aim of this study was to examine verbal fluency changes with a particular focus on the role of cognitive speed. Method. In this study, 28 patients with PD completed measures of verbal fluency, motivation, language, executive functioning, and speed of processing, before and after DBS. Results. As expected, there was a marked decline in verbal fluency but also in a timed test of executive functions and two measures of speed of processing. Verbal fluency decline was associated with markers of linguistic and executive functioning, but not after speed of processing was statistically controlled for. In contrast, greater decline in verbal fluency was associated with higher levels of apathy at baseline, which was not associated with changes in cognitive speed. Discussion. Reduced generativity and processing speed may account for the marked reduction in verbal fluency commonly observed following DBS. PMID:28408788
Lutsey, Pamela L.; Bengtson, Lindsay G.S.; Punjabi, Naresh M.; Shahar, Eyal; Mosley, Thomas H.; Gottesman, Rebecca F.; Wruck, Lisa M.; MacLehose, Richard F.; Alonso, Alvaro
2016-01-01
Study Objectives: Prospective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns. Methods: ARIC participants (n = 966; mean age 61 y, 55% women) with in-home polysomnography (1996–1998) and repeated cognitive testing were followed for 15 y. Three cognitive tests (Delayed Word Recall, Word Fluency, and Digit Symbol Substitution) were administered at two time points (1996–1998 and 2011–2013). Ten additional cognitive tests were administered at the 2011–2013 neurocognitive examination. OSA was modeled using established clinical OSA severity categories. Multivariable linear regression was used to explore associations of OSA and other sleep indices with change in cognitive tests between the two assessments. Results: A median of 14.9 y (max: 17.3) passed between the two cognitive assessments. OSA category and additional indices of sleep (other measures of hypoxemia and disordered breathing, sleep fragmentation, sleep duration) were not associated with change in any cognitive test. Analyses of OSA severity categories and 10 cognitive tests administered only in 2011–2013 also showed little evidence of an association. Conclusions: Overall, abnormal sleep quality and quantity at midlife was not related to cognitive decline and later-life cognition. The effect of adverse sleep quality and quantity on cognitive decline among the elderly remains to be determined. Citation: Lutsey PL, Bengtson LG, Punjabi NM, Shahar E, Mosley TH, Gottesman RF, Wruck LM, MacLehose RF, Alonso A. Obstructive sleep apnea and 15-year cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study. SLEEP 2016;39(2):309–316. PMID:26446113
Crane, Paul K; Gruhl, Jonathan C; Erosheva, Elena A; Gibbons, Laura E; McCurry, Susan M; Rhoads, Kristoffer; Nguyen, Viet; Arani, Keerthi; Masaki, Kamal; White, Lon
2010-11-01
Spoken bilingualism may be associated with cognitive reserve. Mastering a complicated written language may be associated with additional reserve. We sought to determine if midlife use of spoken and written Japanese was associated with lower rates of late life cognitive decline. Participants were second-generation Japanese-American men from the Hawaiian island of Oahu, born 1900-1919, free of dementia in 1991, and categorized based on midlife self-reported use of spoken and written Japanese (total n included in primary analysis = 2,520). Cognitive functioning was measured with the Cognitive Abilities Screening Instrument scored using item response theory. We used mixed effects models, controlling for age, income, education, smoking status, apolipoprotein E e4 alleles, and number of study visits. Rates of cognitive decline were not related to use of spoken or written Japanese. This finding was consistent across numerous sensitivity analyses. We did not find evidence to support the hypothesis that multilingualism is associated with cognitive reserve.
Gruhl, Jonathan C.; Erosheva, Elena A.; Gibbons, Laura E.; McCurry, Susan M.; Rhoads, Kristoffer; Nguyen, Viet; Arani, Keerthi; Masaki, Kamal; White, Lon
2010-01-01
Objectives. Spoken bilingualism may be associated with cognitive reserve. Mastering a complicated written language may be associated with additional reserve. We sought to determine if midlife use of spoken and written Japanese was associated with lower rates of late life cognitive decline. Methods. Participants were second-generation Japanese-American men from the Hawaiian island of Oahu, born 1900–1919, free of dementia in 1991, and categorized based on midlife self-reported use of spoken and written Japanese (total n included in primary analysis = 2,520). Cognitive functioning was measured with the Cognitive Abilities Screening Instrument scored using item response theory. We used mixed effects models, controlling for age, income, education, smoking status, apolipoprotein E e4 alleles, and number of study visits. Results. Rates of cognitive decline were not related to use of spoken or written Japanese. This finding was consistent across numerous sensitivity analyses. Discussion. We did not find evidence to support the hypothesis that multilingualism is associated with cognitive reserve. PMID:20639282
Kats, Dmitry; Patel, Mehul D; Palta, Priya; Meyer, Michelle L; Gross, Alden L; Whitsel, Eric A; Knopman, David; Alonso, Alvaro; Mosley, Thomas H; Heiss, Gerardo
2016-07-01
social support has demonstrated cross-sectional associations with greater cognitive function and a protective effect against cognitive decline in older adults, but exploration of its temporal role in cognitive ageing from mid-life to older adulthood has been limited. We aimed to quantify the associations of social support, assessed at mid-life, with cognitive function in mid-life and with cognitive decline into late life among African Americans and Caucasians. data from the community-based, prospective Atherosclerosis Risk in Communities (ARIC) cohort of 15,792 biracial participants were examined for baseline and longitudinal associations of mid-life social support with global cognition at mid-life and with 20-year change in global cognition, respectively, stratified by race. Interactions with sociodemographic and cardiometabolic covariates were additionally explored within each race group. Social support was ascertained using two metrics: interpersonal support and social network. interpersonal support was directly associated with greater global cognition at baseline in both race groups. Social network was directly associated with greater global cognition at baseline among Caucasians and African American females, but it was not significantly associated with global cognition in African American males. Neither mid-life social support measure was associated with 20-year change in global cognition. higher levels of social support were moderately associated with greater multi-dimensional cognitive function at mid-life, but mid-life social support was not associated with temporal change in global cognitive function over 20 years into late life. Prospective studies with time-dependent measures of social support and cognition are needed to better understand the role of social engagement in ageing-related cognitive functioning. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Jennings, J Richard; Heim, Alicia F; Sheu, Lei K; Muldoon, Matthew F; Ryan, Christopher; Gach, H Michael; Schirda, Claudiu; Gianaros, Peter J
2017-12-01
Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P =0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P =0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife. © 2017 American Heart Association, Inc.
Petruski-Ivleva, Natalia; Kucharska-Newton, Anna; Palta, Priya; Couper, David; Meyer, Katie; Graff, Misa; Haring, Bernhard; Sharrett, Richey; Heiss, Gerardo
2017-10-17
Background : Faster rates of cognitive decline are likely to result in earlier onset of cognitive impairment and dementia. d-galactose, a derivative of lactose, is used in animal studies to induce neurodegeneration. Milk is the primary source of lactose in the human diet, and its effects on cognitive decline have not been fully evaluated. Objective : Assess the association of milk intake with change in cognitive function over 20 years. Methods : A total of 13,751 participants of the Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency questionnaire and three neurocognitive evaluations from 1990 through 2013. Two single nucleotide polymorphisms (SNPs) were used to determine lactase persistence (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models were used to study the association of milk intake with cognitive change. Multiple imputations by chained equations were used to account for attrition. Results : Milk intake greater than 1 glass/day was associated with greater decline in the global z-score over a 20-year period. The difference in decline was 0.10 (95% CI: 0.16, 0.03) z-scores, or an additional 10% decline, relative to the group reporting "almost never" consuming milk. Conclusions : Replication of these results is warranted in diverse populations with greater milk intake and higher variability of lactase persistence genotype.
Petruski-Ivleva, Natalia; Kucharska-Newton, Anna; Palta, Priya; Meyer, Katie; Graff, Misa; Haring, Bernhard; Sharrett, Richey; Heiss, Gerardo
2017-01-01
Background: Faster rates of cognitive decline are likely to result in earlier onset of cognitive impairment and dementia. d-galactose, a derivative of lactose, is used in animal studies to induce neurodegeneration. Milk is the primary source of lactose in the human diet, and its effects on cognitive decline have not been fully evaluated. Objective: Assess the association of milk intake with change in cognitive function over 20 years. Methods: A total of 13,751 participants of the Atherosclerosis Risk in Communities (ARIC) cohort completed a food frequency questionnaire and three neurocognitive evaluations from 1990 through 2013. Two single nucleotide polymorphisms (SNPs) were used to determine lactase persistence (LCT-13910 C/T for Whites and LCT-14010 G/C for Blacks). Mixed-effects models were used to study the association of milk intake with cognitive change. Multiple imputations by chained equations were used to account for attrition. Results: Milk intake greater than 1 glass/day was associated with greater decline in the global z-score over a 20-year period. The difference in decline was 0.10 (95% CI: 0.16, 0.03) z-scores, or an additional 10% decline, relative to the group reporting “almost never” consuming milk. Conclusions: Replication of these results is warranted in diverse populations with greater milk intake and higher variability of lactase persistence genotype. PMID:29039795
Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.
Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence
2018-06-22
Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n = 118) and healthy controls ( n = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy. © AlphaMed Press 2018.
Cognitive functioning and everyday problem solving in older adults.
Burton, Catherine L; Strauss, Esther; Hultsch, David F; Hunter, Michael A
2006-09-01
The relationship between cognitive functioning and a performance-based measure of everyday problem-solving, the Everyday Problems Test (EPT), thought to index instrumental activities of daily living (IADL), was examined in 291 community-dwelling non-demented older adults. Performance on the EPT was found to vary according to age, cognitive status, and education. Hierarchical regression analyses revealed that, after adjusting for demographic and health variables, measures of cognitive functioning accounted for 23.6% of the variance in EPT performance. In particular, measures of global cognitive status, cognitive decline, speed of processing, executive functioning, episodic memory, and verbal ability were significant predictors of EPT performance. These findings suggest that cognitive functioning along with demographic variables are important determinants of everyday problem-solving.
Is air pollution associated with increased risk of cognitive decline? A systematic review.
Peters, Ruth; Peters, Jean; Booth, Andrew; Mudway, Ian
2015-09-01
exposure to air pollution has been shown to increase risk of inflammatory processes and risk of cardiovascular mortality. Such exposure may therefore also be a risk factor for cognitive impairment/dementia. a systematic review of the literature was conducted with databases searched using keywords for air pollution, cognitive decline and dementia. All identified abstracts and potentially relevant articles were double read. For those papers meeting the inclusion criteria, summary tables were prepared and papers quality assessed. from 1,551 abstracts identified, 10 articles were retrieved of which two were rejected. Of the eight remaining six reported prevalent cognitive assessment with historical pollution exposure and two incident cognitive decline, also with historical pollution exposure. In general, an association was reported between exposure and poorer prevalent measures of cognitive function. Data were mixed for incident cognitive decline with one study finding an association and the other not. Reports were limited by a lack of detailed reporting, use of proxy measures of pollution exposure and a lack of clarity regarding cognitive testing methodology and analysis. this systematic review highlights that there is some evidence of a potential association between air pollution and subsequent cognitive decline. Further work is clearly required and longitudinal analysis of ongoing cohort studies or new research would add much needed clarity to this area. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Papathanasiou, Athanasios; Messinis, Lambros; Zampakis, Petros; Papathanasopoulos, Panagiotis
2017-09-01
Cognitive impairment in Multiple Sclerosis (MS) is more frequent and pronounced in secondary progressive MS (SPMS). Cognitive decline is an important predictor of employment status in patients with MS. Magnetic Resonance Imaging (MRI) markers have been used to associate tissue damage with cognitive dysfunction. The aim of the study was to designate the MRI marker that predicts cognitive decline in SPMS and explore its effect on employment status. 30 SPMS patients and 30 healthy participants underwent neuropsychological assessment using the Trail Making Test (TMT) parts A and B, semantic and phonological verbal fluency task and a computerized cognitive screening battery (Central Nervous System Vital Signs). Employment status was obtained as a quality of life measure. Brain MRI was performed in all participants. We measured total lesion volume, third ventricle width, thalamic and corpus callosum atrophy. The frequency of cognitive decline for our SPMS patients was 80%. SPMS patients differed significantly from controls in all neuropsychological measures. Corpus callosum area was correlated with cognitive flexibility, processing speed, composite memory, executive functions, psychomotor speed, reaction time and phonological verbal fluency task. Processing speed and composite memory were the most sensitive markers for predicting employment status. Corpus callosum area was the most sensitive MRI marker for memory and processing speed. Corpus callosum atrophy predicts a clinically meaningful cognitive decline, affecting employment status in our SPMS patients. Copyright © 2017 Elsevier Ltd. All rights reserved.
Motor, cognitive, and functional declines contribute to a single progressive factor in early HD.
Schobel, Scott A; Palermo, Giuseppe; Auinger, Peggy; Long, Jeffrey D; Ma, Shiyang; Khwaja, Omar S; Trundell, Dylan; Cudkowicz, Merit; Hersch, Steven; Sampaio, Cristina; Dorsey, E Ray; Leavitt, Blair R; Kieburtz, Karl D; Sevigny, Jeffrey J; Langbehn, Douglas R; Tabrizi, Sarah J
2017-12-12
To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials. We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up. The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy. Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures. © 2017 American Academy of Neurology.
Zhong, Bao-Liang; Chen, Shu-Lin; Tu, Xin; Conwell, Yeates
2017-01-01
To examine the relationship between loneliness and cognitive function and to explore the mediating role of physical health on the loneliness-cognition relationship in Chinese older adults (OAs). Data came from a nationally representative sample of 14,199 Chinese OAs (aged 65+) from 2002, 2005, 2008, and 2011 waves of the Chinese Longitudinal Healthy Longevity Survey. A latent variable cross-lagged panel model combined with mediation analysis was used to determine the relationship between loneliness and cognitive function and the mediating effect of increase in the number of chronic conditions (ΔNCCs) on the ascertained loneliness-cognition relationship. Severe loneliness at prior assessment points was significantly associated with poorer cognitive function at subsequent assessments, and vice versa. The ΔNCCs partially mediated this prospective reciprocal relationships, accounting for 2.58% of the total effect of loneliness on cognition and 4.44% of the total effect of cognition on loneliness, respectively. Loneliness may predict subsequent cognitive decline, and vice versa. This loneliness-cognition relationship is partially explained by their impact on physical health. Multidisciplinary interventions aimed at reducing loneliness and cognitive decline per se and their associated risk factors as well as improving chronic illness management would be beneficial for emotional well-being and cognitive health in OAs. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Forli, F.; Guglielmi, V.; De Corso, E.; Paludetti, G.; Berrettini, S.; Fetoni, A.R.
2016-01-01
SUMMARY Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research. PMID:27214827
A decade of changes in brain volume and cognition.
Aljondi, Rowa; Szoeke, Cassandra; Steward, Chris; Yates, Paul; Desmond, Patricia
2018-05-09
Brain atrophy can occur several decades prior to onset of cognitive impairments. However, few longitudinal studies have examined the relationship between brain volume changes and cognition over a long follow-up period in healthy elderly women. In the present study we investigate the relationship between whole brain and hippocampal atrophy rates and longitudinal changes in cognition, including verbal episodic memory and executive function, in older women. We also examine whether baseline brain volume predicts subsequent changes in cognitive performance over a 10-year period. A total of 60 individuals from the population-based Women's Healthy Ageing Project with a mean age at baseline of 59 years underwent 3T MRI. Of these, 40 women completed follow-up cognitive assessments, 23 of whom had follow-up MRI scans. Linear regression analysis was used to examine the relationship between brain atrophy and changes in verbal episodic memory and executive function over a 10-year period. The results show that baseline measurements of frontal and temporal grey matter volumes predict changes in verbal episodic memory performance, whereas hippocampal volume at baseline is associated with changes in executive function performance over a 10-year period of follow-ups. In addition, higher whole brain and hippocampal atrophy rates are correlated with a decline in verbal episodic memory. These findings indicate that in addition to atrophy rate, smaller regional grey matter volumes even 10 years prior is associated with increased rates of cognitive decline. This study suggests useful neuroimaging biomarkers for the prediction of cognitive decline in healthy elderly women.
Effect of Vitamin Intake on Cognitive Decline in Older Adults: Evaluation of the Evidence.
Krause, D; Roupas, P
2015-08-01
The objective of this review was to evaluate the evidence from human studies on the intake of vitamins, either as monotherapies or in combination with other vitamins, as neuroprotective agents that may delay the onset of cognitive decline in older adults. Evidence-based methodologies were used to capture and evaluate the highest levels of evidence. The current evidence available showed no association for cognitive benefits of vitamins B6 or B12 as a monotherapy, and recent systematic reviews provide no clear evidence that supplementation with vitamin B6, B12 and/or folic acid improves dementia outcomes or slows cognitive decline, even though it may normalise homocysteine levels. Meta-analyses from systematic reviews have shown an association between low vitamin D levels and diminished cognitive function, although causality cannot be confirmed from the available evidence. There is no convincing evidence for an association of vitamin A, vitamin C or vitamin E either as a monotherapy or in combination with other antioxidant vitamins such as β-carotene and the prevention of cognitive decline. The appraisal of nineteen systematic reviews and meta-analyses has highlighted the heterogeneity between studies, and the need for better consensus on definitions of cognitive decline, duration of testing and agreement on which specific endpoints are clinically relevant. Evaluation of the totality of the currently available evidence indicates that intake of the above vitamins, either as a monotherapy, or in combination with other vitamins, has no clinically-relevant effect on delaying cognitive decline or delaying the onset of dementia in older adults.
Radiation Effects on Cognitive Function Among Atomic Bomb Survivors Exposed at or After Adolescence.
Yamada, Michiko; Landes, Reid D; Mimori, Yasuyo; Nagano, Yoshito; Sasaki, Hideo
2016-06-01
The objective of this study was to investigate radiation effects on longitudinal pre-dementia cognitive decline among participants who developed dementia as well as on those who did not develop dementia during follow-up. Measuring cognitive function with the Cognitive Abilities Screening Instrument approximately every 2 years, we followed 1844 atomic bomb survivors participating in the Adult Health Study of the Radiation Effects Research Foundation from 1992 to 2011. Participants were adolescents or older when exposed to between 0 and 4 Gy. Approximately 15% and 40% of participants were exposed to ≥1 Gy and <5 mGy, respectively. At study start, participants were dementia-free and between 60 and 80 years old. Three-quarters of the participants returned after baseline, averaging 8.4 years of follow-up. During follow-up, 313 developed dementia. We used cognitive scores before dementia onset for analysis and a mixed-effects model to estimate radiation effects on longitudinal change of cognition, adjusting for dementia occurrence, age, sex, and education. Cognition level was significantly associated with age, education, and dementia occurrence but not with radiation dose or sex. Cognitive decline accelerated with increasing age, especially among participants who developed dementia. Neither radiation nor education was significantly associated with the degree of deterioration with age. Radiation did not modify the different cognitive decline by dementia occurrence. Radiation did not significantly affect cognition among atomic bomb survivors exposed at or after adolescence. Copyright © 2016 Elsevier Inc. All rights reserved.
Olfaction Is Related to Motor Function in Older Adults.
Tian, Qu; Resnick, Susan M; Studenski, Stephanie A
2017-08-01
Among older adults, both olfaction and motor function predict future cognitive decline and dementia, suggesting potential shared causal pathways. However, it is not known whether olfactory and motor function are independently related in late life. We assessed cross-sectional associations of olfaction with motor and cognitive function, using concurrent data on olfactory function, mobility, balance, fine motor function, manual dexterity, and cognition in 163 Baltimore Longitudinal Study of Aging participants aged 60 and older without common neurological diseases (n = 114 with available cognitive data). Using multiple linear regression, we adjusted for age, sex, race, smoking history, height, and weight for mobility and balance, and education for cognition. We used multiple linear regression to test whether olfaction-motor associations were independent of cognition and depressive symptoms. Olfactory scores were significantly associated with mobility (usual gait speed, rapid gait speed, 400-m walk time, and Health ABC Physical Performance Battery score), balance, fine motor function, and manual dexterity (all p < .05). In those with available cognitive data, additional adjustment for depressive symptoms, verbal memory, or visuoperceptual speed demonstrated especially strong independent relationships with challenging motor tasks such as 400-m walk and nondominant hand manual dexterity (p < .005). This study demonstrates for the first time that, in older adults, olfactory function is associated with mobility, balance, fine motor function, and manual dexterity, and independent of cognitive function, with challenging upper and lower extremity motor function tasks. Longitudinal studies are needed to determine if olfactory performance predicts future mobility and functional decline. Published by Oxford University Press on behalf of The Gerontological Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Impact of Education on Memory Deficits in Subclinical Depression
McLaren, Molly E.; Szymkowicz, Sarah M.; Kirton, Joshua W.; Dotson, Vonetta M.
2015-01-01
Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18–81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon. PMID:26109434
BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention
Boots, Elizabeth A.; Schultz, Stephanie A.; Clark, Lindsay R.; Racine, Annie M.; Darst, Burcu F.; Koscik, Rebecca L.; Carlsson, Cynthia M.; Gallagher, Catherine L.; Hogan, Kirk J.; Bendlin, Barbara B.; Asthana, Sanjay; Sager, Mark A.; Hermann, Bruce P.; Christian, Bradley T.; Dubal, Dena B.; Engelman, Corinne D.; Johnson, Sterling C.
2017-01-01
Objective: To examine the influence of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether β-amyloid (Aβ) burden plays a moderating role in this relationship. Methods: One thousand twenty-three adults (baseline age 54.94 ± 6.41 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent BDNF genotyping and cognitive assessment at up to 5 time points (average follow-up 6.92 ± 3.22 years). A subset (n = 140) underwent 11C-Pittsburgh compound B (PiB) scanning. Covariate-adjusted mixed-effects regression models were used to elucidate the effect of BDNF on cognitive trajectories in 4 cognitive domains, including verbal learning and memory, speed and flexibility, working memory, and immediate memory. Secondary mixed-effects regression models were conducted to examine whether Aβ burden, indexed by composite PiB load, modified any observed BDNF-related cognitive trajectories. Results: Compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory (p = 0.002) and speed and flexibility (p = 0.017). In addition, Aβ burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aβ burden showed even steeper cognitive decline (p = 0.033). Conclusions: In a middle-aged cohort with AD risk, carriage of the BDNF Met allele was associated with steeper decline in episodic memory and executive function. This decline was exacerbated by greater Aβ burden. These results suggest that the BDNF Val66Met polymorphism may play an important role in cognitive decline and could be considered as a target for novel AD therapeutics. PMID:28468845
BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention.
Boots, Elizabeth A; Schultz, Stephanie A; Clark, Lindsay R; Racine, Annie M; Darst, Burcu F; Koscik, Rebecca L; Carlsson, Cynthia M; Gallagher, Catherine L; Hogan, Kirk J; Bendlin, Barbara B; Asthana, Sanjay; Sager, Mark A; Hermann, Bruce P; Christian, Bradley T; Dubal, Dena B; Engelman, Corinne D; Johnson, Sterling C; Okonkwo, Ozioma C
2017-05-30
To examine the influence of the brain-derived neurotrophic factor ( BDNF ) Val66Met polymorphism on longitudinal cognitive trajectories in a large, cognitively healthy cohort enriched for Alzheimer disease (AD) risk and to understand whether β-amyloid (Aβ) burden plays a moderating role in this relationship. One thousand twenty-three adults (baseline age 54.94 ± 6.41 years) enrolled in the Wisconsin Registry for Alzheimer's Prevention underwent BDNF genotyping and cognitive assessment at up to 5 time points (average follow-up 6.92 ± 3.22 years). A subset (n = 140) underwent 11 C-Pittsburgh compound B (PiB) scanning. Covariate-adjusted mixed-effects regression models were used to elucidate the effect of BDNF on cognitive trajectories in 4 cognitive domains, including verbal learning and memory, speed and flexibility, working memory, and immediate memory. Secondary mixed-effects regression models were conducted to examine whether Aβ burden, indexed by composite PiB load, modified any observed BDNF -related cognitive trajectories. Compared to BDNF Val/Val homozygotes, Met carriers showed steeper decline in verbal learning and memory ( p = 0.002) and speed and flexibility ( p = 0.017). In addition, Aβ burden moderated the relationship between BDNF and verbal learning and memory such that Met carriers with greater Aβ burden showed even steeper cognitive decline ( p = 0.033). In a middle-aged cohort with AD risk, carriage of the BDNF Met allele was associated with steeper decline in episodic memory and executive function. This decline was exacerbated by greater Aβ burden. These results suggest that the BDNF Val66Met polymorphism may play an important role in cognitive decline and could be considered as a target for novel AD therapeutics. © 2017 American Academy of Neurology.
Association between plasma phenolics and improved cognition in blueberry-supplemented older adults
USDA-ARS?s Scientific Manuscript database
Research in both human and animals has demonstrated that cognitive function decreases during aging. These functional declines may be caused by long-term increases in and susceptibility to oxidative stress and inflammation. A growing body of research shows that dietary supplementation with blueberrie...
Price, Catherine C.; Levy, Shellie-Anne; Tanner, Jared; Garvan, Cyndi; Ward, Jade; Akbar, Farheen; Bowers, Dawn; Rice, Mark; Okun, Michael
2016-01-01
BACKGROUND Post-operative cognitive dysfunction (POCD) demarks cognitive decline after major surgery but has been studied to date in “healthy” adults. Although individuals with neurodegenerative disorders such as Parkinson’s disease (PD) commonly undergo elective surgery, these individuals have yet to be prospectively followed despite hypotheses of increased POCD risk. OBJECTIVE To conduct a pilot study examining cognitive change pre-post elective orthopedic surgery for PD relative to surgery and non-surgery peers. METHODS A prospective one-year longitudinal design. No-dementia idiopathic PD individuals were actively recruited along with non-PD “healthy” controls (HC) undergoing knee replacement surgery. Non-surgical PD and HC controls were also recruited. Attention/processing speed, inhibitory function, memory recall, animal (semantic) fluency, and motor speed were assessed at baseline (pre-surgery), three-weeks, three-months, and one-year post- orthopedic surgery. Reliable change methods examined individual changes for PD individuals relative to control surgery and control non-surgery peers. RESULTS Over two years we screened 152 older adult surgery or non-surgery candidates with 19 of these individuals having a diagnosis of PD. Final participants included 8 PD (5 surgery, 3 non-surgery), 47 Control Surgery, and 21 Control Non-Surgery. Eighty percent (4 of the 5) PD surgery declined greater than 1.645 standard deviations from their baseline performance on measures assessing processing speed and inhibitory function. This was not observed for the non-surgery PD individuals. CONCLUSION This prospective pilot study demonstrated rationale and feasibility for examining cognitive decline in at-risk neurodegenerative populations. We discuss recruitment and design challenges for examining post-operative cognitive decline in neurodegenerative samples. PMID:26683785
Shift work and cognition in the Nurses' Health Study.
Devore, Elizabeth E; Grodstein, Francine; Schernhammer, Eva S
2013-10-15
Rotating night-shift work, which can disrupt circadian rhythm, may adversely affect long-term health. Experimental studies indicate that circadian rhythm disruption might specifically accelerate brain aging; thus, we prospectively examined shift-work history at midlife as associated with cognitive function among older women in the Nurses' Health Study. Women reported their history of rotating night-shift work in 1988 and participated in telephone-based cognitive interviews between 1995 and 2001; interviews included 6 cognitive tests that were subsequently repeated 3 times, at 2-year intervals. We focused on shift work through midlife (here, ages 58-68 years) because cognitive decline is thought to begin during this period. Using multivariable-adjusted linear regression, we evaluated mean differences in both "average cognitive status" at older age (averaging cognitive scores from all 4 interviews) and rates of cognitive decline over time across categories of shift-work duration at midlife (none, 1-9, 10-19, or ≥20 years). There was little association between shift work and average cognition in later life or between shift work and cognitive decline. Overall, this study does not clearly support the hypothesis that shift-work history in midlife has long-term effects on cognition in older adults.
APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline
Wang, Yamin; Barnes, Lisa L.; Tangney, Christine; Bennett, David A.; Morris, Martha Clare
2016-01-01
Objective: To examine the association between consumption of seafood and long-chain n-3 fatty acids with change in 5 cognitive domains over an average of 4.9 years. Methods: From an ongoing longitudinal, community-based epidemiologic study of aging and dementia (the Rush Memory and Aging Project), we included 915 participants (age 81.4 ± 7.2 years, 25% men) who had completed at least one follow-up cognitive assessment and dietary data. Diet was assessed by semiquantitative food frequency questionnaire. Scores for global cognitive function and 5 cognitive domains (episodic, semantic, and working memory, perceptual speed, and visuospatial ability) were assessed using 19 cognitive tests. Mixed models adjusted for multiple risk factors of cognitive change were used to assess the associations. Results: Consumption of seafood was associated with slower decline in semantic memory (β = 0.024; p = 0.03) and perceptual speed (β = 0.020; p = 0.05) in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain n-3 fatty acid intake from food. These associations were not present in APOE ε4 noncarriers. Higher intake levels of α-linolenic acid were associated with slower global cognitive decline, but also only in APOE ε4 carriers. Conclusions: These results suggest protective relations of one meal per week of seafood and long-chain n-3 fatty acids against decline in multiple cognitive domains. The role of APOE ε4 in this association needs further study. PMID:27164694
Rattanabannakit, Chatchawan; Risacher, Shannon L; Gao, Sujuan; Lane, Kathleen A; Brown, Steven A; McDonald, Brenna C; Unverzagt, Frederick W; Apostolova, Liana G; Saykin, Andrew J; Farlow, Martin R
2016-01-01
The perception of cognitive decline by individuals and those who know them well ("informants") has been inconsistently associated with objective cognitive performance, but strongly associated with depressive symptoms. We investigated associations of self-report, informant-report, and discrepancy between self- and informant-report of cognitive decline obtained from the Cognitive Change Index (CCI) with cognitive test performance and self-reported depressive symptoms. 267 participants with normal cognition, mild cognitive impairment (MCI), or mild dementia were included from a cohort study and memory clinic. Association of test performance and self-rated depression (Geriatric Depression Scale, GDS) with CCI scores obtained from subjects (CCI-S), their informants (CCI-I), and discrepancy scores between subjects and informants (CCI-D; CCI-S minus CCI-I) were analyzed using correlation and analysis of covariance (ANCOVA) models. CCI-S and CCI-I scores showed high internal consistency (Cronbach alpha 0.96 and 0.98, respectively). Higher scores on CCI-S and CCI-I, and lower scores on the CCI-D, were associated with lower performance on various cognitive tests in both univariate and in ANCOVA models adjusted for age, gender, and education. Adjustment for GDS slightly weakened the relationships between CCI and test performance but most remained significant. Self- and informant-report of cognitive decline, as measured by the CCI, show moderately strong relationships with objective test performance independent of age, gender, education, and depressive symptoms. The CCI appears to be a valid cross-sectional measure of self and informant perception of cognitive decline across the continuum of functioning. Studies are needed to address the relationship of CCI scores to longitudinal outcome.
Identifying elderly people at risk for cognitive decline by using the 2-step test.
Maruya, Kohei; Fujita, Hiroaki; Arai, Tomoyuki; Hosoi, Toshiki; Ogiwara, Kennichi; Moriyama, Shunnichiro; Ishibashi, Hideaki
2018-01-01
[Purpose] The purpose is to verify the effectiveness of the 2-step test in predicting cognitive decline in elderly individuals. [Subjects and Methods] One hundred eighty-two participants aged over 65 years underwent the 2-step test, cognitive function tests and higher level competence testing. Participants were classified as Robust, <1.3, and <1.1 using criteria regarding the locomotive syndrome risk stage for the 2-step test, variables were compared between groups. In addition, ordered logistic analysis was used to analyze cognitive functions as independent variables in the three groups, using the 2-step test results as the dependent variable, with age, gender, etc. as adjustment factors. [Results] In the crude data, the <1.3 and <1.1 groups were older and displayed lower motor and cognitive functions than did the Robust group. Furthermore, the <1.3 group exhibited significantly lower memory retention than did the Robust group. The 2-step test was related to the Stroop test (β: 0.06, 95% confidence interval: 0.01-0.12). [Conclusion] The finding is that the risk stage of the 2-step test is related to cognitive functions, even at an initial risk stage. The 2-step test may help with earlier detection and implementation of prevention measures for locomotive syndrome and mild cognitive impairment.
A Lifespan Approach to Neuroinflammatory and Cognitive Disorders: A Critical Role for Glia
Bilbo, Staci D.; Smith, Susan H.; Schwarz, Jaclyn M.
2011-01-01
Cognitive decline is a common problem of aging. Whereas multiple neural and glial mechanisms may account for these declines, microglial sensitization and/or dystrophy has emerged as a leading culprit in brain aging and dysfunction. However, glial activation is consistently observed in normal brain aging as well, independent of frank neuroinflammation or functional impairment. Such variability suggests the existence of additional vulnerability factors that can impact neuronal-glial interactions and thus overall brain and cognitive health. The goal of this review is to elucidate our working hypothesis that an individual‘s risk or resilience to neuroinflammatory disorders and poor cognitive aging may critically depend on their early life experience, which can change immune reactivity within the brain for the remainder of the lifespan. For instance, early-life infection in rats can profoundly disrupt memory function in young adulthood, as well as accelerate age-related cognitive decline, both of which are linked to enduring changes in glial function that occur in response to the initial infection. We discuss these findings within the context of the growing literature on the role of immune molecules and neuroimmune crosstalk in normal brain development. We highlight the intrinsic factors (e.g., chemokines, hormones) that regulate microglial development and their colonization of the embryonic and postnatal brain, and the capacity for disruption or “re-programming” of this crucial process by external events (e.g, stress, infection). An impact on glia, which in turn alters neural development, has the capacity to profoundly impact cognitive and mental health function at all stages of life. PMID:21822589
Cognitive changes in people with temporal lobe epilepsy over a 13-year period.
Mameniškienė, Rūta; Rimšienė, Justė; Puronaitė, Roma
2016-10-01
The aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13years and to determine what clinical and treatment characteristics may have been associated with these. Thirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13years earlier. There was no significant change in verbal and verbal-logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal-logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal-logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal-logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression. Over a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study. Copyright © 2016 Elsevier Inc. All rights reserved.
Zhang, Fan; Luo, Jie; Min, Su; Ren, Li; Qin, Peipei
2016-07-01
This study investigated the effects of propofol and electroconvulsive shock (ECS), the analogue of electroconvulsive therapy (ECT) in animals, on tissue plasminogen activator (tPA) and its inhibitor (PAI-1) as well as the precursor of brain-derived neurotrophic factor (proBDNF)/mature BDNF (mBDNF) ratio in depressive rats. ECT is an effective treatment for depression, but can cause cognitive deficit. Some studies have indicated that propofol can ameliorate cognitive decline induced by ECT, but the underlying molecular mechanism is still unclear. Recent evidence has found that mBDNF and its precursor proBDNF are related to depression and cognitive function; they elicit opposite effects on cellular functions. Chronic unpredicted mild stress is widely used to induce depressive behaviors in rodents. This study found that the depression resulted in an increased expression of PAI-1 and upregulation of the proBDNF/mBDNF ratio, together with a decreased level of tPA, long-term potentiation (LTP) impairment, and cognitive decline. The proBDNF/mBDNF ratio was further upregulated after the ECS treatment in depressive rats, resulting in the deterioration of cognitive function and hippocampal LTP. Propofol alone did not reverse the changes in depressive rats, but when co-administered with ECS, it improved the cognitive function, alleviated the impairment of LTP, downregulated the proBDNF/mBDNF ratio, and increased the tPA expression. The results of this study suggest that propofol ameliorates cognitive decline induced by ECT, which was partly by modulating the proBDNF/mBDNF ratio and reversing the excessive changes in hippocampal synaptic plasticity, providing a new evidence for involving the proBDNF/mBDNF system in the progression and treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.
de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel
2016-01-01
Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67–90] years old; n = 20) compared with young controls (median 35 [27–40] years old; n = 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p = .001), IL1-β (p = .001), IL-6 (p = .002), and IL-8 (p = .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID:26286603
Dhillon, Jaapna; Tan, Sze-Yen; Mattes, Richard D
2017-02-01
The post-lunch dip in cognition is a well-established phenomenon of decreased alertness, memory and vigilance after lunch consumption. Lunch composition reportedly influences the post-lunch dip. Moreover, dieting is associated with cognitive function impairments. The negative effects of dieting have been reversed with nut-supplemented diets. The aims of this study were to (1) evaluate the acute effect of an almond-enriched high-fat lunch or high-carbohydrate lunch on the post-lunch decline in cognitive function, and (2) evaluate the effects of chronic almond consumption as part of an energy-restricted diet on the memory and attention domains of cognitive function. In total, eighty-six overweight and obese adults were randomised to consume either an almond-enriched diet (AED) or a nut-free control diet (NFD) over a 12-week weight loss intervention. Participants were also randomised to receive either an almond-enriched high-fat lunch (A-HFL) (>55 % energy from fat, almonds contributing 70-75 % energy) or a high-carbohydrate lunch (HCL) (>85 % energy from carbohydrates) at the beginning and end of the weight loss intervention. Memory and attention performance indices decreased after lunch consumption (P<0·001). The A-HFL group ameliorated the decline in memory scores by 57·7 % compared with the HCL group (P=0·004). Both lunch groups had similar declines in attention. Moreover, memory and attention performance indices increased after the 12-week intervention period (P<0·05) with no difference between the AED and NFD groups. In conclusion, almond consumption at a midday meal can reduce the post-lunch dip in memory. However, long-term almond consumption may not further improve cognitive function outcomes in a weight loss intervention.
Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S; Lyketsos, Constantine G
2012-04-01
We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright © 2011 John Wiley & Sons, Ltd.
Knight, Alissa; Bryan, Janet; Murphy, Karen
2016-01-01
The rise in the ageing population has resulted in increased incident rates of cognitive impairment and dementia. The subsequent financial and societal burden placed on an already strained public health care system is of increasing concern. Evidence from recent studies has revealed modification of lifestyle and dietary behaviours is, at present, the best means of prevention. Some of the most important findings, in relation to the Mediterranean diet (MedDiet) and the contemporary Western diet, and potential molecular mechanisms underlying the effects of these two diets on age-related cognitive function, are discussed in this review. A major aim of this review was to discuss whether or not a MedDiet intervention would be a feasible preventative approach against cognitive decline for older adults living in Western countries. Critical appraisal of the literature does somewhat support this idea. Demonstrated evidence highlights the MedDiet as a potential strategy to reduce cognitive decline in older age, and suggests the Western diet may play a role in the aetiology of cognitive decline. However, strong intrinsic Western socio-cultural values, traditions and norms may impede on the feasibility of this notion. Copyright © 2015 Elsevier B.V. All rights reserved.
Dynamic hub load predicts cognitive decline after resective neurosurgery.
Carbo, Ellen W S; Hillebrand, Arjan; van Dellen, Edwin; Tewarie, Prejaas; de Witt Hamer, Philip C; Baayen, Johannes C; Klein, Martin; Geurts, Jeroen J G; Reijneveld, Jaap C; Stam, Cornelis J; Douw, Linda
2017-02-07
Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of 'hub (over)load', caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning.
Both odor identification and ApoE-ε4 contribute to normative cognitive aging.
Finkel, Deborah; Reynolds, Chandra A; Larsson, Maria; Gatz, Margaret; Pedersen, Nancy L
2011-12-01
Research indicates that apoliprotein E (ApoE) plays a role in the development of Alzheimer's disease (AD) and possibly in the cognitive decline associated with normative aging. More recently, researchers have shown that ApoE is expressed in olfactory brain structures, and a relationship among ApoE, AD, and olfactory function has been proposed. In the current analyses, we investigated the contribution of ApoE and odor identification in decline trajectories associated with normative cognitive aging in various domains, using longitudinal data on cognitive performance available from the Swedish Adoption/Twin Study of Aging. Data on both ApoE status and olfactory functioning were available from 455 individuals ranging in age from 50 to 88 years at the first measurement occasion. Odor identification was measured via a mailed survey. Cognitive performance was assessed in up to 5 waves of in-person testing covering a period of 16 years. Latent growth curve analyses incorporating odor identification and ApoE status indicated a main effect of odor identification on the performance level in three cognitive domains: verbal, memory, and speed. A main effect of ApoE on rates of decline after age 65 was found for verbal, spatial, and speed factors. The consistency of results across cognitive domains provides support for theories that posit central nervous system-wide origins of the olfaction-cognition-ApoE relationship; however, olfactory errors and APOE ε4 show unique and differential effects on cognitive trajectory features.
Xu, F; Delmonico, M J; Lofgren, I E; Uy, K M; Maris, S A; Quintanilla, D; Taetzsch, A G; Letendre, J; Mahler, L
2017-01-01
Cognitive decline in older adults is a major public health problem and can compromise independence and quality of life. Exercise and diet have been studied independently and have shown to be beneficial for cognitive function, however, a combined Tai Chi, resistance training, and diet intervention and its influence on cognitive function has not been undertaken. The current study used a 12-week non-randomized research design with experiment and control groups to examine the effect of a combined Tai Chi, resistance training, and diet intervention on cognitive function in 25 older obese women. Results revealed improvements in domain specific cognitive function in our sample. Baseline cognitive function was correlated with changes in dietary quality. These findings suggest that Tai Chi and resistance training combined with diet intervention might be beneficial for community-based programs aiming to improve cognitive function.
Dementia Risk and Financial Decision Making by Older Households: The Impact of Information
Hsu, Joanne W.; Willis, Robert
2014-01-01
The knowledge and reasoning ability needed to manage one’s finances is a form of human capital. Alzheimer’s disease and other dementias cause progressive declines in cognition that lead to a complete loss of functional capacities. In this paper we analyze the impact of information about cognitive decline on the choice of household financial decision-maker. Using longitudinal data on older married couples in a novel application of survival analysis, we find that as the financial decision maker’s cognition declines, the management of finances is eventually turned over to his cognitively intact spouse, often well after difficulties handling money have already emerged. However, a memory disease diagnosis increases the hazard of switching the financial respondent by over 200 percent for couples who control their retirement accounts, like 401(k) accounts, relative to those who passively receive retirement income. This finding is consistent with a model of the value of information: households with the most to gain financially from preparation are most responsive to information about cognitive decline. PMID:25525476
Lopez-Fontana, Iréné; Castanier, Carole; Le Scanff, Christine; Perrot, Alexandra
2018-06-13
This study aimed to investigate if the impact of both recent and long-term physical activity on age-related cognitive decline would be modified by sex. One-hundred thirty-five men (N = 67) and women (N = 68) aged 18 to 80 years completed the Modifiable Activity Questionnaire and the Historical Leisure Activity Questionnaire. A composite score of cognitive functions was computed from five experimental tasks. Hierarchical regression analyses performed to test the moderating effect of recent physical activity on age-cognition relationship had not revealed significant result regardless of sex. Conversely, past long-term physical activity was found to slow down the age-related cognitive decline among women (β = 0.22, p = .03), but not men. The findings support a lifecourse approach in identifying determinants of cognitive aging and the importance of taking into account the moderating role of sex. This article presented potential explanations for these moderators and future avenues to explore.
Trumble, Benjamin C.; Stieglitz, Jonathan; Blackwell, Aaron D.; Allayee, Hooman; Beheim, Bret; Finch, Caleb E.; Gurven, Michael; Kaplan, Hillard
2017-01-01
The apolipoprotein E4 (E4) allele is present worldwide, despite its associations with higher risk of cardiovascular morbidity, accelerated cognitive decline during aging, and Alzheimer’s disease (AD). The E4 allele is especially prevalent in some tropical regions with a high parasite burden. Equatorial populations also face a potential dual burden of high E4 prevalence combined with parasitic infections that can also reduce cognitive performance. We examined the interactions of E4, parasite burden, and cognitive performance in a traditional, nonindustrialized population of Amazonian forager-horticulturalists (N = 372) to test whether E4 protects against cognitive decline in environments with a heavy pathogen burden. Contrary to observations in industrial populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas non-E4 carriers with a high parasite burden showed reduced cognitive performance. Being an E4 carrier is the strongest risk factor to date of AD and cognitive decline in industrial populations; it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions. The current mismatch between postindustrial hygienic lifestyles and active parasite-rich environs may be critical for understanding genetic risk for cognitive aging.—Trumble, B. C., Stieglitz, J., Blackwell, A. D., Allayee, H., Beheim, B., Finch, C. E., Gurven, M., Kaplan, H. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. PMID:28031319
Trumble, Benjamin C; Stieglitz, Jonathan; Blackwell, Aaron D; Allayee, Hooman; Beheim, Bret; Finch, Caleb E; Gurven, Michael; Kaplan, Hillard
2017-04-01
The apolipoprotein E4 (E4) allele is present worldwide, despite its associations with higher risk of cardiovascular morbidity, accelerated cognitive decline during aging, and Alzheimer 's disease (AD). The E4 allele is especially prevalent in some tropical regions with a high parasite burden. Equatorial populations also face a potential dual burden of high E4 prevalence combined with parasitic infections that can also reduce cognitive performance. We examined the interactions of E4, parasite burden, and cognitive performance in a traditional, nonindustrialized population of Amazonian forager-horticulturalists ( N = 372) to test whether E4 protects against cognitive decline in environments with a heavy pathogen burden. Contrary to observations in industrial populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas non-E4 carriers with a high parasite burden showed reduced cognitive performance. Being an E4 carrier is the strongest risk factor to date of AD and cognitive decline in industrial populations; it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions. The current mismatch between postindustrial hygienic lifestyles and active parasite-rich environs may be critical for understanding genetic risk for cognitive aging.-Trumble, B. C., Stieglitz, J., Blackwell, A. D., Allayee, H., Beheim, B., Finch, C. E., Gurven, M., Kaplan, H. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. © FASEB.
USDA-ARS?s Scientific Manuscript database
Older adults experience a variety of functional changes that decrease their quality of life with age-related cognitive decline and reduced mobility being of particular concern. Pre-clinical research indicates that berry fruit offer a promising dietary approach to preserving nervous system function, ...
Cognitive dysfunction in multiple sclerosis: a review of recent developments.
Bobholz, Julie A; Rao, Stephen M
2003-06-01
Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.
Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline
Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; ...
2017-02-08
The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less
Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.
The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less
Which Neuropsychological Tests Predict Progression to Alzheimer’s Disease in Hispanics?
Weissberger, Gali H.; Salmon, David P.; Bondi, Mark W.; Gollan, Tamar H.
2013-01-01
Objective To investigate which neuropsychological tests predict eventual progression to Alzheimer’s disease (AD) in both Hispanic and non-Hispanic individuals. Although our approach was exploratory, we predicted that tests that underestimate cognitive ability in healthy aging Hispanics might not be sensitive to future cognitive decline in this cultural group. Method We compared first-year data of 22 older adults (11 Hispanic) who were diagnosed as cognitively normal but eventually developed AD (decliners), to 60 age- and education-matched controls (27 Hispanic) who remained cognitively normal. To identify tests that may be culturally biased in our sample, we compared Hispanic with non-Hispanic controls on all tests and asked which tests were sensitive to future decline in each cultural group. Results Compared to age-, education-, and gender-matched non-Hispanic controls, Hispanic controls obtained lower scores on tests of language, executive function, and some measures of global cognition. Consistent with our predictions, some tests identified non-Hispanic, but not Hispanic, decliners (vocabulary, semantic fluency). Contrary to our predictions, a number of tests on which Hispanics obtained lower scores than non-Hispanics nevertheless predicted eventual progression to AD in both cultural groups (e.g., Boston Naming Test [BNT], Trails A and B). Conclusions Cross-cultural variation in test sensitivity to decline may reflect greater resistance of medium difficulty items to decline and bilingual advantages that initially protect Hispanics against some aspects of cognitive decline commonly observed in non-Hispanics with preclinical AD. These findings highlight a need for further consideration of cross-cultural differences in neuropsychological test performance and development of culturally unbiased measures. PMID:23688216
Gates, Nicola J; Valenzuela, Michael; Sachdev, Perminder S; Singh, Nalin A; Baune, Bernhard T; Brodaty, Henry; Suo, Chao; Jain, Nidhi; Wilson, Guy C; Wang, Yi; Baker, Michael K; Williamson, Dominique; Foroughi, Nasim; Fiatarone Singh, Maria A
2011-04-21
The extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown. This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training (CT) and progressive resistance training (PRT) on general cognitive function and functional independence in older adults with early cognitive impairment: Study of Mental and Regular Training (SMART). Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function, cardiovascular and metabolic function, exercise capacity, psychological state and body composition, to identify the potential mechanisms of benefit and broader health status effects. SMART is a double-blind randomized, double sham-controlled trial. One hundred and thirty-two community-dwelling volunteers will be recruited. Primary inclusion criteria are: at risk for cognitive decline as defined by neuropsychology assessment, low physical activity levels, stable disease, and age over 55 years. The two active interventions are computerized CT and whole body, high intensity PRT. The two sham interventions are educational videos and seated calisthenics. Participants are randomized into 1 of 4 supervised training groups (2 d/wk×6 mo) in a fully factorial design. Primary outcomes measured at baseline, 6, and 18 months are the Alzheimer's Disease Assessment Scale (ADAS-Cog), neuropsychological test scores, and Bayer Informant Instrumental Activities of Daily Living (B-IADLs). Secondary outcomes are psychological well-being, quality of life, cardiovascular and musculoskeletal function, body composition, insulin resistance, systemic inflammation and anabolic/neurotrophic hormones, and brain morphology and function via Magnetic Resonance Imaging (MRI) and Spectroscopy (fMRS). SMART will provide a novel evaluation of the immediate and long term benefits of CT, PRT, and combined CT and PRT on global cognitive function and brain morphology, as well as potential underlying mechanisms of adaptation in older adults at risk of further cognitive decline. Australia and New Zealand Clinical Trials Register (ANZCTR): ANZCTRN12608000489392.
2011-01-01
Background The extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown. This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training (CT) and progressive resistance training (PRT) on general cognitive function and functional independence in older adults with early cognitive impairment: Study of Mental and Regular Training (SMART). Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function, cardiovascular and metabolic function, exercise capacity, psychological state and body composition, to identify the potential mechanisms of benefit and broader health status effects. Methods SMART is a double-blind randomized, double sham-controlled trial. One hundred and thirty-two community-dwelling volunteers will be recruited. Primary inclusion criteria are: at risk for cognitive decline as defined by neuropsychology assessment, low physical activity levels, stable disease, and age over 55 years. The two active interventions are computerized CT and whole body, high intensity PRT. The two sham interventions are educational videos and seated calisthenics. Participants are randomized into 1 of 4 supervised training groups (2 d/wk × 6 mo) in a fully factorial design. Primary outcomes measured at baseline, 6, and 18 months are the Alzheimer's Disease Assessment Scale (ADAS-Cog), neuropsychological test scores, and Bayer Informant Instrumental Activities of Daily Living (B-IADLs). Secondary outcomes are psychological well-being, quality of life, cardiovascular and musculoskeletal function, body composition, insulin resistance, systemic inflammation and anabolic/neurotrophic hormones, and brain morphology and function via Magnetic Resonance Imaging (MRI) and Spectroscopy (fMRS). Discussion SMART will provide a novel evaluation of the immediate and long term benefits of CT, PRT, and combined CT and PRT on global cognitive function and brain morphology, as well as potential underlying mechanisms of adaptation in older adults at risk of further cognitive decline. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR): ANZCTRN12608000489392 PMID:21510896
Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta
2018-01-01
Background: There has been little research conducted regarding cognitive treatments for the elderly postsurgical population. Patients aged ≥60 years have an increased risk of postoperative cognitive decline, a condition in which cognitive functions are negatively affected. This cognitive decline can lead to a decline in quality of life. In order to maintain a high quality of life, the elderly postsurgical population may benefit from treatment to maintain and/or improve their cognitive functions. This pilot study investigates the effect of simple calculation and reading aloud (SCRA) cognitive training in elderly Japanese postsurgical patients. Methods: Elderly patients undergoing non-cardiovascular thoracic surgery under general anesthesia were recruited ( n = 12). Subjects were randomly divided into two groups-one that receives 12 weeks of SCRA intervention, and a waitlisted control group. Before and after the intervention, we measured cognitive function [Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), computerized Cogstate Brief Battery (CBB)] and emotional state [General Health Questionnaire-12 (GHQ-12), Geriatric Depression Scale (GDS), Quality of Life Scale-5 (QOL-5)]. Results: Group difference analyses using ANCOVA with permutation test showed that the intervention SCRA group had a significant improvement in FAB motor programming sub-score, GDS, and QOL-5 compared to the control group. Within-group analyses using Wilcoxon signed-rank test to compare baseline and follow-up showed that the SCRA intervention group total FAB scores, FAB motor programming sub-scores, and QOL-5 scores were significantly improved. Discussion: This pilot study showed that there are important implications for the beneficial effects of SCRA intervention on cognitive function and emotional state in the postoperative elderly population; however, further investigations are necessary to reach any conclusions. Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000019832).
Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta
2018-01-01
Background: There has been little research conducted regarding cognitive treatments for the elderly postsurgical population. Patients aged ≥60 years have an increased risk of postoperative cognitive decline, a condition in which cognitive functions are negatively affected. This cognitive decline can lead to a decline in quality of life. In order to maintain a high quality of life, the elderly postsurgical population may benefit from treatment to maintain and/or improve their cognitive functions. This pilot study investigates the effect of simple calculation and reading aloud (SCRA) cognitive training in elderly Japanese postsurgical patients. Methods: Elderly patients undergoing non-cardiovascular thoracic surgery under general anesthesia were recruited (n = 12). Subjects were randomly divided into two groups—one that receives 12 weeks of SCRA intervention, and a waitlisted control group. Before and after the intervention, we measured cognitive function [Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), computerized Cogstate Brief Battery (CBB)] and emotional state [General Health Questionnaire-12 (GHQ-12), Geriatric Depression Scale (GDS), Quality of Life Scale-5 (QOL-5)]. Results: Group difference analyses using ANCOVA with permutation test showed that the intervention SCRA group had a significant improvement in FAB motor programming sub-score, GDS, and QOL-5 compared to the control group. Within-group analyses using Wilcoxon signed-rank test to compare baseline and follow-up showed that the SCRA intervention group total FAB scores, FAB motor programming sub-scores, and QOL-5 scores were significantly improved. Discussion: This pilot study showed that there are important implications for the beneficial effects of SCRA intervention on cognitive function and emotional state in the postoperative elderly population; however, further investigations are necessary to reach any conclusions. Trial registration: This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000019832). PMID:29643802
Physical Activity as a Moderator of the Relationship between Aging and Inductive Reasoning
ERIC Educational Resources Information Center
Perrot, Alexandra; Gagnon, Christine; Bertsch, Jean
2009-01-01
A relatively universal observation in aging studies is that cognitive functions inevitably decline across the adult life span. More specifically, executive functions decline substantially with age, as do the frontal and prefrontal brain regions that support them. Indeed, these regions are subject to important neurological modifications with…
Ginkgo biloba for Preventing Cognitive Decline in Older Adults
Snitz, Beth E.; O'Meara, Ellen S.; Carlson, Michelle C.; Arnold, Alice M.; Ives, Diane G.; Rapp, Stephen R.; Saxton, Judith; Lopez, Oscar L.; Dunn, Leslie O.; Sink, Kaycee M.; DeKosky, Steven T.
2010-01-01
Context The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning. Objective To determine whether G biloba slows the rates of global or domain-specific cognitive decline in older adults. Design, Setting, and Participants The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years. Intervention Twice-daily dose of 120-mg extract of G biloba (n=1545) or identical-appearing placebo (n=1524). Main Outcome Measures Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests. Results Annual rates of decline in z scores did not differ between G biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P=.71; for ADAS-Cog, P=.97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P>.05). Conclusion Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment. Trial Registration clinicaltrials.gov Identifier: NCT00010803 PMID:20040554
Fujiwara, Esther; Brand, Matthias; Borsutzky, Sabine; Steingass, Hans-P; Markowitsch, Hans J
2008-07-01
Excessive alcohol consumption is assumed to promote cognitive decline, eventually increasing the risk of dementia. However, little is known about the time course of cognitive functions in patients with chronic alcoholic Korsakoff syndrome (KS). Therefore, we assessed neuropsychological performance in 20 detoxified chronic KS inpatients at time 1 (T1) with a follow-up after two years (T2). The neuropsychological tests assessed verbal and visual short- and long-term memory, working memory, basic executive functions, language, general knowledge, and visual-spatial abilities. Surveys with caregivers and medical records provided information about current and previous disease-related parameters, drinking history, additional pathologies, as well as psychosocial and cognitive therapy within the two-year period. At both sessions, the majority of the KS patients' results were inferior to those of normal subjects. Comparing T1 and T2 revealed no significant decline in any of the investigated functions. Instead, general knowledge, visual long-term memory, and verbal fluency improved slightly after two years, though they still remained within pathological range. Comparing most improved and most deteriorated patients, better outcome occurred more frequently in men than women and was associated with higher premorbid education and fewer detoxifications in the past. In this sample of detoxified KS patients there was no indication of accelerated cognitive decline or onset of dementia-like symptoms over two years.
Can Training in a Real-Time Strategy Videogame Attenuate Cognitive Decline in Older Adults?
Basak, Chandramallika; Boot, Walter R.; Voss, Michelle W.; Kramer, Arthur F.
2014-01-01
Declines in various cognitive abilities, particularly executive control functions, are observed in older adults. An important goal of cognitive training is to slow or reverse these age-related declines. However, opinion is divided in the literature regarding whether cognitive training can engender transfer to a variety of cognitive skills in older adults. Yet, recent research indicates that videogame training of young adults may engender broad transfer to skills of visual attention. In the current study, we used a real-time strategy videogame to attempt to train executive functions in older adults, such as working memory, task switching, short-term memory, inhibition, and reasoning. Older adults were either trained in a real-time strategy videogame for 23.5 hours (RON, n=20) or not (CONTROLS, n=20). A battery of cognitive tasks, including tasks of executive control and visuo-spatial skills, were assessed before, during, and after video game training. The trainees improved significantly in the measures of game performance. They also improved significantly more than the controls in a subset of the cognitive tasks, such as task switching, working memory, visual short term memory, and mental rotation. Trends in improvement were also observed, for the video game trainees, in inhibition and reasoning. Individual differences in changes in game performance were correlated with improvements in task-switching. The study has implications for the enhancement of executive control processes of older adults. PMID:19140648
Steiber, Nadia
2015-01-01
This paper uses individual-level data from the German Socio-Economic Panel to model trends in population health in terms of cognition, physical fitness, and mental health between 2006 and 2012. The focus is on the population aged 50–90. We use a repeated population-based cross-sectional design. As outcome measures, we use SF-12 measures of physical and mental health and the Symbol-Digit Test (SDT) that captures cognitive processing speed. In line with previous research we find a highly significant Flynn effect on cognition; i.e., SDT scores are higher among those who were tested more recently (at the same age). This result holds for men and women, all age groups, and across all levels of education. While we observe a secular improvement in terms of cognitive functioning, at the same time, average physical and mental health has declined. The decline in average physical health is shown to be stronger for men than for women and found to be strongest for low-educated, young-old men aged 50–64: the decline over the 6-year interval in average physical health is estimated to amount to about 0.37 SD, whereas average fluid cognition improved by about 0.29 SD. This pattern of results at the population-level (trends in average population health) stands in interesting contrast to the positive association of physical health and cognitive functioning at the individual-level. The findings underscore the multi-dimensionality of health and the aging process. PMID:26323093
Leung, Grace Tak Yu; Fung, Ada Wai Tung; Tam, Cindy Woon Chi; Lui, Victor Wing Cheong; Chiu, Helen Fung Kum; Chan, Wai Man; Lam, Linda Chiu Wa
2011-01-01
This study examines the association between late-life leisure activity participation and global cognitive decline in community-dwelling elderly Chinese in Hong Kong. Five hundred and five participants, not clinically demented at the baseline, were analysed in the follow-up study of a population-based community survey among Hong Kong Chinese aged 60 and over. Information regarding leisure activity participation, global cognitive function and important sociodemographic variables was collected. Late life leisure activity profiles were classified into intellectual, social, physical and recreational categories, and were measured by total hours per week, total frequency and total number of subtypes. Multivariate logistic regression analyses were used to evaluate the association between leisure activity participation at the baseline and the incidence of global cognitive decline at the 22-month follow-up. The incidence of global cognitive decline was defined as a one-point drop in z-score of the Cantonese version of the mini-mental state examination (CMMSE). At the follow-up, a higher level of participation in intellectual activities was significantly associated with a lower incidence of global cognitive decline as measured by both the total hours per week (multivariate-adjusted OR 0.97 (95% CI 0.94-0.99, p=0.003)), and the total number of subtypes (multivariate-adjusted OR 0.74 (95% CI 0.58-0.95, p=0.018)). A higher level of late-life intellectual activity participation was associated with less global cognitive decline among community-dwelling elderly Chinese in Hong Kong. Copyright © 2010 John Wiley & Sons, Ltd.
Feng, Xiaomei; Degos, Vincent; Koch, Lauren G; Britton, Steven L; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn
2013-05-01
Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.
Cognitive function and advanced kidney disease: longitudinal trends and impact on decision-making.
Iyasere, Osasuyi; Okai, David; Brown, Edwina
2017-02-01
Background: Cognitive impairment commonly affects renal patients. But little is known about the influence of dialysis modality on cognitive trends or the influence of cognitive impairment on decision-making in renal patients. This study evaluated cognitive trends amongst chronic kidney disease (CKD), haemodialysis (HD) and peritoneal dialysis (PD) patients. The relationship between cognitive impairment and decision-making capacity (DMC) was also assessed. Methods: Patients were recruited from three outpatient clinics. Cognitive function was assessed 4-monthly for up to 2 years, using the Montreal Cognitive Assessment (MoCA) tool. Cognitive trends were assessed using mixed model analysis. DMC was assessed using the Macarthur Competency Assessment tool (MacCAT-T). MacCAT-T scores were compared between patients with cognitive impairment (MoCA <26) and those without. Results: In total, 102 (41 HD, 25 PD and 36 CKD) patients were recruited into the prospective study. After multivariate analysis, the total MoCA scores declined faster in dialysis compared with CKD patients [coefficient = -0.03, 95% confidence interval (95% CI) = -0.056 to - 0.004; P = 0.025]. The MoCA executive scores declined faster in the HD compared with PD patients (coefficient = -0.12, 95% CI = -0.233 to - 0.007; P = 0.037). DMC was assessed in 10 patients. Those with cognitive impairment had lower MacCAT-T compared with those without [median (interquartile range) 19 (17.9-19.6) versus 17.4 (16.3-18.4); P = 0.049]. Conclusions: Cognition declines faster in dialysis patients compared with CKD patients and in HD patients compared with PD patients. Cognitive impairment affects DMC in patients with advanced kidney disease.
Carrière, Isabelle; Norton, Joanna; Farré, Amandine; Wyart, Marilyn; Tzourio, Christophe; Noize, Pernelle; Pérès, Karine; Fourrier-Réglat, Annie; Ritchie, Karen; Ancelin, Marie Laure
2017-04-19
Cognitive impairment is very common in late-life depression, principally affecting executive skills and information processing speed. The aim of the study was to examine the effect of antidepressant treatment on cognitive performances over a 10-year period. The community-based cohort included 7381 participants aged 65 years and above. Five cognitive domains (verbal fluency, psychomotor speed, executive function, visuospatial skills and global cognition) were assessed up to five times over 10 years of follow-up. Treatment groups included participants under a specific antidepressant class at both baseline and the first follow-up and their follow-up cognitive data were considered until the last consecutive follow-up with a report of antidepressant use of the same class. Linear mixed models were used to compare baseline cognitive performance and cognitive decline over time according to antidepressant treatment. The models were adjusted for multiple confounders including residual depressive symptoms assessed by the Center for Epidemiologic Studies-Depression scale. At baseline, 4.0% of participants were taking antidepressants. Compared to non-users, tricyclic antidepressant users had lower baseline performances in verbal fluency, visual memory and psychomotor speed, and selective serotonin reuptake inhibitor users in verbal fluency and psychomotor speed. For the two other cognitive abilities, executive function and global cognition, no significant differences were found at baseline irrespective of the antidepressant class. Regarding changes over time, no significant differences were observed in comparison with non-users whatever the cognitive domain, except for a slight additional improvement over the follow-up in verbal fluency skills for tricyclic antidepressant users. In this large elderly general population cohort, we found no evidence for an association between antidepressant use and post-treatment cognitive decline over 10 years of follow-up in various cognitive domains.
Loneliness, depression and cognitive function in older U.S. adults.
Donovan, Nancy J; Wu, Qiong; Rentz, Dorene M; Sperling, Reisa A; Marshall, Gad A; Glymour, M Maria
2017-05-01
To examine reciprocal relations of loneliness and cognitive function in older adults. Data were analyzed from 8382 men and women, age 65 and older, participating in the US Health and Retirement Study from 1998 to 2010. Participants underwent biennial assessments of loneliness and depression (classified as no, low or high depression) determined by the Center for Epidemiologic Studies Depression scale (8-item version), cognition (a derived memory score based on a word list memory task and proxy-rated memory and global cognitive function), health status and social and demographic characteristics from 1998 to 2010. We used repeated measures analysis to examine the reciprocal relations of loneliness and cognitive function in separate models controlling sequentially and cumulatively for socio-demographic factors, social network, health conditions and depression. Loneliness at baseline predicted accelerated cognitive decline over 12 years independent of baseline socio-demographic factors, social network, health conditions and depression (β = -0.2, p = 0.002). After adjustment for depression interacting with time, both low and high depression categories were related to faster cognitive decline and the estimated effect of loneliness became marginally significant. Reciprocally, poorer cognition at baseline was associated with greater odds of loneliness over time in adjusted analyses (OR 1.3, 95% CI (1.1-1.5) p = 0.005), but not when controlling for baseline depression. Furthermore, cognition did not predict change in loneliness over time. Examining longitudinal data across a broad range of cognitive abilities, loneliness and depressive symptoms appear to be related risk factors for worsening cognition but low cognitive function does not lead to worsening loneliness over time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Zhang, Xiuming; Mormino, Elizabeth C; Sun, Nanbo; Sperling, Reisa A; Sabuncu, Mert R; Yeo, B T Thomas
2016-10-18
We used a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural MRIs of late-onset Alzheimer's disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus, and amygdala), a subcortical atrophy factor (striatum, thalamus, and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal, and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, whereas the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared with temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Factor compositions of participants and code used in this article are publicly available for future research.
The Aging Mind: Potential and Limits.
ERIC Educational Resources Information Center
Baltes, Paul B.
1993-01-01
Notes that research on aging mind has moved from simple growth versus decline view to conception of joint consideration of potential and limits. Sees this development illustrated by research on two categories of cognitive functioning: the cognitive mechanics (comparable to fluid intelligence) and cognitive pragmatics (comparable to crystallized…
Effects of strawberry supplementation on mobility and cognition in older adults
USDA-ARS?s Scientific Manuscript database
During aging, functional changes in the central and peripheral nervous system can alter mobility and cognition - in some cases leading to early cognitive decline, disability, or injurious falls among older adults. Previously, we have shown that two months of dietary supplementation with berry fruit...
Mobility and cognition: End points for dietary interventions in aging
USDA-ARS?s Scientific Manuscript database
BACKGROUND: Healthy aging is associated with functional declines in mobility and cognition among both humans and non-human animals. OBJECTIVE: This study combines human measures of mobility and cognition to develop a test battery for evaluating the effects of dietary supplements among older adults....
Frick, Karyn M.
2012-01-01
A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women. PMID:22289043
Zammit, Andrea R; Robitaille, Annie; Piccinin, Andrea; Muniz-Terrera, Graciela; Hofer, Scott M
2018-03-08
Grip strength and cognitive function reflect upper body muscle strength and mental capacities. Cross-sectional research has suggested that in old age these two processes are moderately to highly associated, and that an underlying common cause drives this association. Our aim was to synthesize and evaluate longitudinal research addressing whether changes in grip strength are associated with changes in cognitive function in healthy older adults. We systematically reviewed English-language research investigating the longitudinal association between repeated measures of grip strength and of cognitive function in community-dwelling older adults to evaluate the extent to which the two indices decline concurrently. We used four search engines: Embase, PsychINFO, PubMed, and Web of Science. Of 459 unique citations, 6 met our full criteria: 4 studies reported a longitudinal association between rates of change in grip strength and cognitive function in older adults, 2 of which reported the magnitudes of these associations as ranging from low to moderate; 2 studies reported significant cross-sectional but not longitudinal associations among rates of change. All studies concluded that cognitive function and grip strength declined, on average, with increasing age, although with little to no evidence for longitudinal associations among rates of change. Future research is urged to expand the study of physical and cognitive associations in old age using a within-person and multi-study integrative approach to evaluate the reliability of longitudinal results with greater emphasis on the magnitude of this association.
Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome.
Shapiro, Elsa G; Whitley, Chester B; Eisengart, Julie B
2018-05-11
Hurler syndrome (MPS IH), the severe, neurodegenerative form of type one mucopolysaccharidosis, is associated with rapid neurocognitive decline during toddlerhood and multi-system dysfunction. It is now standardly treated with hematopoietic cell transplantation (HCT), which halts accumulating disease pathology and prevents early death. While norm-based data on developmental functioning in untreated children have previously demonstrated neurocognitive decline, advances in methodology for understanding the cognitive functioning of children with neurodegenerative diseases have highlighted that the previous choice of scores to report results was not ideal. Specifically, the lowest possible norm-based score is 50, which obscures the complete range of cognitive functioning at more advanced stages of neurodeterioration. To a set of cognitive data collected on a sample of untreated children, we applied a modern method of score analysis, calculating a developmental quotient based on age equivalent scores, to reveal the full range of cognitive functioning beneath this cutoff of 50, uncovering new information about the rapidity of decline and the profound impairment in these children. Among 39 observations for 32 patients with untreated Hurler syndrome, the full array of cognitive functioning below 50 includes many children in the severely to profoundly impaired range. The loss of skills per time unit was 14 points between age 1 and 2. There was a very large range of developmental quotients corresponding to the norm-based cutoff of 50. This report enables clarification of functioning at levels that extend beneath the floor of 50 in previous work. At the dawn of newborn screening and amidst a proliferation of new therapies for MPS I, these data can provide crucial benchmark information for developing treatments, particularly for areas of the world where transplant may not be available.
Cognitive Decline and Older Driver Crash Risk.
Fraade-Blanar, Laura A; Ebel, Beth E; Larson, Eric B; Sears, Jeanne M; Thompson, Hilaire J; Chan, Kwun Chuen G; Crane, Paul K
2018-04-17
To examine automobile crash risk associated with cognition in older drivers without dementia. Retrospective secondary analysis of longitudinal cohort study. Our study used data from the Adult Changes in Thought (ACT) Study merged with Washington State crash reports and licensure records. Data were available from 2002 to 2015. Group Health enrollees from Washington State aged 65 and older with active driver's licenses (N=2,615). Cognitive function was assessed using the Cognitive Abilities Screening Instrument scored using item response theory (CASI-IRT). The study outcome was police-reported motor vehicle crash. We used a negative binomial mixed-effects model with robust standard errors clustered on the individual and considered associations between crash risk, level of cognition, and amount of decline since the previous study visit. Covariates included age, sex, education, alcohol, depression, medical comorbidities, eyesight, hearing, and physical function. Individuals were censored at dementia diagnosis, death, or failure to renew their license. Over an average of 7 years of follow-up, 350 (13%) people had at least one crash. A 1-unit lower CASI-IRT score was associated with a higher adjusted incidence rate ratio of crash of 1.26 (95% confidence interval=1.08-1.51). Beyond level of cognition, amount of cognitive decline between study visits was not associated with crash risk. This study suggests that, in older drivers, poorer performance on the CASI-IRT may be a risk factor for motor vehicle crashes, even in individuals without diagnosed dementia. Further research is needed to understand driving behavior and inform driving decisions for older adults with poor cognitive function. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.
Leach, Julia M.; Mancini, Martina; Kaye, Jeffrey A.; Hayes, Tamara L.; Horak, Fay B.
2018-01-01
Introduction: Increased variability in motor function has been observed during the initial stages of cognitive decline. However, the natural variability of postural control, as well as its association with cognitive status and decline, remains unknown. The objective of this pilot study was to characterize the day-to-day variability in postural sway in non-demented older adults. We hypothesized that older adults with a lower cognitive status would have higher day-to-day variability in postural sway. Materials and Methods: A Nintendo Wii balance board (WBB) was used to quantify postural sway in the home twice daily for 30 days in 20 non-demented, community-dwelling older adults: once under a single-task condition and once under a dual-task condition (using a daily word search task administered via a Nook tablet). Mean sway distance, velocity, area, centroidal frequency and frequency dispersion were derived from the center of pressure data acquired from the WBB. Results: Linear relationships were observed between the day-to-day variability in postural sway and cognitive status (indexed by cognitive global z-scores). More variability in time-domain postural sway (sway distance and area) and less variability in frequency-domain postural sway (centroidal sway frequency) were associated with a lower cognitive status under both the single- and dual-task conditions. Additionally, lower cognitive performance rates on the daily word search task were related to a lower cognitive status. Discussion: This small pilot study conducted on a short time scale motivates large-scale implementations over more extended time periods. Tracking longitudinal changes in postural sway may further our understanding of early-stage postural decline and its association with cognitive decline and, in turn, may aid in the early detection of dementia during preclinical stages when the utility of disease-modifying therapies would be greatest. PMID:29780319
Leach, Julia M; Mancini, Martina; Kaye, Jeffrey A; Hayes, Tamara L; Horak, Fay B
2018-01-01
Introduction : Increased variability in motor function has been observed during the initial stages of cognitive decline. However, the natural variability of postural control, as well as its association with cognitive status and decline, remains unknown. The objective of this pilot study was to characterize the day-to-day variability in postural sway in non-demented older adults. We hypothesized that older adults with a lower cognitive status would have higher day-to-day variability in postural sway. Materials and Methods : A Nintendo Wii balance board (WBB) was used to quantify postural sway in the home twice daily for 30 days in 20 non-demented, community-dwelling older adults: once under a single-task condition and once under a dual-task condition (using a daily word search task administered via a Nook tablet). Mean sway distance, velocity, area, centroidal frequency and frequency dispersion were derived from the center of pressure data acquired from the WBB. Results : Linear relationships were observed between the day-to-day variability in postural sway and cognitive status (indexed by cognitive global z-scores). More variability in time-domain postural sway (sway distance and area) and less variability in frequency-domain postural sway (centroidal sway frequency) were associated with a lower cognitive status under both the single- and dual-task conditions. Additionally, lower cognitive performance rates on the daily word search task were related to a lower cognitive status. Discussion : This small pilot study conducted on a short time scale motivates large-scale implementations over more extended time periods. Tracking longitudinal changes in postural sway may further our understanding of early-stage postural decline and its association with cognitive decline and, in turn, may aid in the early detection of dementia during preclinical stages when the utility of disease-modifying therapies would be greatest.
Terminal-decline effects for select cognitive tasks after controlling for preclinical dementia.
Laukka, Erika J; MacDonald, Stuart W S; Bäckman, Lars
2008-05-01
In a previous study, the authors found no accelerated decline in close proximity to death for a measure of global cognitive functioning, after excluding persons in a preclinical phase of dementia. However, specific cognitive tasks might be more sensitive to terminal-decline effects. The purpose of this study was to explore possible terminal-decline effects for a range of cognitive tasks after controlling for preclinical dementia. Community-based cohort study. The Kungsholmen district of Stockholm. A total of 585 persons (75+ years) were repeatedly assessed over an 11-year period. Level and change in cognitive performance were compared for three groups: persons in close proximity to death, persons in a preclinical phase of dementia, and persons who remained alive and nondemented throughout the study. Tasks assessing primary and episodic memory, verbal ability, and visuospatial skill. Compared with an analysis where all dead subjects were included in the impending-death group, removing the preclinical dementia cases resulted in markedly attenuated mortality-related effects. However, the impending-death group still declined at a faster rate relative to the comparison group on Digit Span-forward, word recognition, and category fluency. Notably, these were tasks for which the comparison group showed no significant decline. A considerable proportion of the terminal-decline effect is accounted for by the impact of preclinical dementia. However, for tasks that are relatively resistant to age-related change, such effects might be detected independently of preclinical dementia.
Brain volume change and cognitive trajectories in aging.
Fletcher, Evan; Gavett, Brandon; Harvey, Danielle; Farias, Sarah Tomaszewski; Olichney, John; Beckett, Laurel; DeCarli, Charles; Mungas, Dan
2018-05-01
Examine how longitudinal cognitive trajectories relate to brain baseline measures and change in lobar volumes in a racially/ethnically and cognitively diverse sample of older adults. Participants were 460 older adults enrolled in a longitudinal aging study. Cognitive outcomes were measures of episodic memory, semantic memory, executive function, and spatial ability derived from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent variable multilevel modeling of the four cognitive outcomes as parallel longitudinal processes identified intercepts for each outcome and a second order global change factor explaining covariance among the highly correlated slopes. We examined how baseline brain volumes (lobar gray matter, hippocampus, and white matter hyperintensity) and change in brain volumes (lobar gray matter) were associated with cognitive intercepts and global cognitive change. Lobar volumes were dissociated into global and specific components using latent variable methods. Cognitive change was most strongly associated with brain gray matter volume change, with strong independent effects of global gray matter change and specific temporal lobe gray matter change. Baseline white matter hyperintensity and hippocampal volumes had significant incremental effects on cognitive decline beyond gray matter change. Baseline lobar gray matter was related to cognitive decline, but did not contribute beyond gray matter change. Cognitive decline was strongly influenced by gray matter volume change and, especially, temporal lobe change. The strong influence of temporal lobe gray matter change on cognitive decline may reflect involvement of temporal lobe structures that are critical for late life cognitive health but also are vulnerable to diseases of aging. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Chen, L-Y; Liu, L-K; Hwang, A-C; Lin, M-H; Peng, L-N; Chen, L-K; Lan, C-F; Chang, P-L
2016-01-01
To evaluate the prevalence of malnutrition and its impact on mortality, functional decline and cognitive impairment among elder residents in long-term care settings. A prospective cohort study. Two veteran homes in Taiwan. A total of 1,248 male residents aged equal or more than 65 years. Charlson's comorbidity index (CCI), Minimum data set (MDS), resident assessment protocols (RAP), Activity of daily living-Hierarchy scale, Cognitive Performance Scale, MDS Social engagement scale. The mean age of participants is 83.1 ± 5.1 years, and the prevalence of malnutrition was 6.1%. Inadequate dietary content (57.9%) and unintentional weight loss (31.6%) account for the majority of malnutrition identified by MDS tool. Higher 18-month mortality rate (25% vs. 14.2%), higher baseline CCI (median 1 vs. 0), and higher baseline sum of RAP triggers (median 8.5 vs. 5) were noted among residents with malnutrition. Furthermore, malnutrition was shown predictive for functional decline (OR: 3.096, 95% CI: 1.715-5.587) and potential cognitive improvement (OR: 2.469, 95% CI: 1.188-5.128) among survivors after adjustment for age, body mass index and CCI. Malnutrition among elder men residing in veteran homes was associated with multimorbidities and higher care complexity, and was predictive for mortality and functional decline.
Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta
2017-01-01
Background: This pilot study investigated the effects of partial pulmonary lobectomy lung surgery on cognitive functions of elderly Japanese patients. It is recognized that elderly patients undergoing surgery have increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery is aging. Methods: Cognitive function was measured for all subjects (n = 12) before and after surgery using three different cognitive tests: Mini-Mental Status Exam-Japanese (MMSE-J), Frontal Assessment Battery (FAB), and a computerized Cogstate Brief Battery (CBB). Changes in these measures indicate changes in cognitive function. In addition, the 12-item General Health Questionnaire (GHQ-12), the Geriatric Depression Scale (GDS), and the 5-item Quality of Life questionnaire (QOL-5) were administered at each time point to measure mental and emotional state. Changes in outcome measures were analyzed via Wilcoxon signed-rank test. Exploratory correlation analysis was conducted using Spearman’s rho. Results: Data show a decline in detection (DET; p = 0.045) and identification (IDN; p = 0.038). Spearman’s correlation coefficient show a significant correlation between postoperative DET scores and postoperative IDN scores (ρ = 0.78, p = 0.005), a significant correlation between change in IDN and baseline GHQ-12 scores (ρ = -0.595, p = 0.027), and a significant correlation between change in one-back (OBK) scores and duration of anesthesia (ρ = -0.72, p = 0.012). Discussion: This was the first report to examine cognitive decline after major thoracic surgery in Japanese patients. Previous studies have evidenced that POCD is a common phenomenon after surgery, and that age is a major risk factor. The CCB measured significant change in two cognitive domains: attention and psycomotor function. This study clarified that decline in cognition is detectable in certain measures after thoracic surgery in the elderly Japanese patient population. Additionally, longer anesthetic exposure may negatively impact attention and working memory, and preoperative mental wellbeing is a possible predictor of POCD. These preliminary results have important implications and support the need for future studies. PMID:29259553
Bilello, Michel; Doshi, Jimit; Nabavizadeh, S. Ali; Toledo, Jon B.; Erus, Guray; Xie, Sharon X.; Trojanowski, John Q.; Han, Xiaoyan; Davatzikos, Christos
2015-01-01
Background Vascular risk factors are increasingly recognized as risks factors for Alzheimer’s disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. Objective To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Methods Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. Results CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Conclusion Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly. PMID:26402108
Bilello, Michel; Doshi, Jimit; Nabavizadeh, S Ali; Toledo, Jon B; Erus, Guray; Xie, Sharon X; Trojanowski, John Q; Han, Xiaoyan; Davatzikos, Christos
2015-01-01
Vascular risk factors are increasingly recognized as risks factors for Alzheimer's disease (AD) and early conversion from mild cognitive impairment (MCI) to dementia. While neuroimaging research in AD has focused on brain atrophy, metabolic function, or amyloid deposition, little attention has been paid to the effect of cerebrovascular disease to cognitive decline. To investigate the correlation of brain atrophy and white matter lesions with cognitive decline in AD, MCI, and control subjects. Patients with AD and MCI, and healthy subjects were included in this study. Subjects had a baseline MRI scan, and baseline and follow-up neuropsychological battery (CERAD). Regional volumes were measured, and white matter lesion segmentation was performed. Correlations between rate of CERAD score decline and white matter lesion load and brain structure volume were evaluated. In addition, voxel-based correlations between baseline CERAD scores and atrophy and white matter lesion measures were computed. CERAD rate of decline was most significantly associated with lesion loads located in the fornices. Several temporal lobe ROI volumes were significantly associated with CERAD decline. Voxel-based analysis demonstrated strong correlation between baseline CERAD scores and atrophy measures in the anterior temporal lobes. Correlation of baseline CERAD scores with white matter lesion volumes achieved significance in multilobar subcortical white matter. Both baseline and declines in CERAD scores correlate with white matter lesion load and gray matter atrophy. Results of this study highlight the dominant effect of volume loss, and underscore the importance of small vessel disease as a contributor to cognitive decline in the elderly.
ERIC Educational Resources Information Center
Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.
2014-01-01
Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…
Bilingualism does not alter cognitive decline or dementia risk among Spanish-speaking immigrants.
Zahodne, Laura B; Schofield, Peter W; Farrell, Meagan T; Stern, Yaakov; Manly, Jennifer J
2014-03-01
Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared with monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially nondemented Hispanic immigrants living in a Spanish-speaking enclave of northern Manhattan. Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18-24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in 4 domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However, bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve. PsycINFO Database Record (c) 2014 APA, all rights reserved.
Bilingualism Does Not Alter Cognitive Decline or Dementia Risk among Spanish-Speaking Immigrants
Zahodne, Laura B.; Schofield, Peter W.; Farrell, Meagan T.; Stern, Yaakov; Manly, Jennifer J.
2013-01-01
Objective Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared to monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially non-demented Hispanic immigrants living in a Spanish-speaking enclave of Northern Manhattan. Method Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18–24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in four domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. Results Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. Conclusions This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve. PMID:24188113
Leisure-time physical activity associates with cognitive decline
Willey, Joshua Z.; Gardener, Hannah; Caunca, Michelle R.; Moon, Yeseon Park; Dong, Chuanhui; Cheung, Yuen K.; Sacco, Ralph L.; Elkind, Mitchell S.V.
2016-01-01
Objective: Because leisure-time physical activity (LTPA) is protective against incident dementia, we hypothesized that LTPA is protective against decline in domain-specific cognitive performance. Methods: As part of the Northern Manhattan Study, LTPA was ascertained at enrollment using a validated in-person questionnaire. We assessed cognition in participants in the Northern Manhattan Study MRI substudy using a standard neuropsychological examination (NPE) (n = 1,228), and a repeat examination was performed 5 years later (n = 876). LTPA was summarized as the maximum intensity of any activity performed, classified as none to light intensity (physical inactivity) (90%) vs moderate to heavy intensity (10%). The NPE was subcategorized using standardized z scores over validated domains: processing speed, semantic memory, episodic memory, and executive function. We used multivariable linear regression models to examine the association of LTPA with initial and change in cognitive performance. Analyses were adjusted for sociodemographics, cardiovascular disease risk factors, and MRI findings (white matter hyperintensity volume, silent brain infarcts, cerebral volume). Results: No/low levels of LTPA were associated with worse executive function, semantic memory, and processing speed scores on the first NPE. The associations were slightly attenuated and no longer significant after adjusting for vascular risk factors. Cognitively unimpaired participants reporting no/low LTPA vs moderate/high levels declined more over time in processing speed (β = −0.231 ± 0.112, p = 0.040) and episodic memory (β = −0.223 ± 0.117, p = 0.057) adjusting for sociodemographic and vascular risk factors. Conclusions: A low level of LTPA is independently associated with greater decline in cognitive performance over time across domains. PMID:27009261
Schweizer, Tom A; Vogel-Sprott, Muriel
2008-06-01
Much research on the effects of a dose of alcohol has shown that motor skills recover from impairment as blood alcohol concentrations (BACs) decline and that acute tolerance to alcohol impairment can develop during the course of the dose. Comparable alcohol research on cognitive performance is sparse but has increased with the development of computerized cognitive tasks. This article reviews the results of recent research using these tasks to test the development of acute tolerance in cognitive performance and recovery from impairment during declining BACs. Results show that speed and accuracy do not necessarily agree in detecting cognitive impairment, and this mismatch most frequently occurs during declining BACs. Speed of cognitive performance usually recovers from impairment to drug-free levels during declining BACs, whereas alcohol-increased errors fail to diminish. As a consequence, speed of cognitive processing tends to develop acute tolerance, but no such tendency is shown in accuracy. This "acute protracted error" phenomenon has not previously been documented. The findings pose a challenge to the theory of alcohol tolerance on the basis of physiological adaptation and raise new research questions concerning the independence of speed and accuracy of cognitive processes, as well as hemispheric lateralization of alcohol effects. The occurrence of alcohol-induced protracted cognitive errors long after speed returned to normal is identified as a potential threat to the safety of social drinkers that requires urgent investigation.
Cognitive decline and survival in Alzheimer's disease according to education level.
Bruandet, A; Richard, F; Bombois, S; Maurage, C A; Masse, I; Amouyel, P; Pasquier, F
2008-01-01
We tested the hypothesis that a higher education level is associated with faster cognitive decline and lower survival in a cohort of 670 Alzheimer's disease patients, followed for 3.5 years at the Lille-Bailleul memory centre. The patients were categorized in 3 groups according to educational levels: low (
Brain Morphology Links Systemic Inflammation to Cognitive Function in Midlife Adults
Marsland, Anna L.; Gianaros, Peter J.; Kuan, Dora C-H.; Sheu, Lei K.; Krajina, Katarina; Manuck, Stephen B.
2015-01-01
Background Inflammation is linked to cognitive decline in midlife, but the neural basis for this link is unclear. One possibility is that inflammation associates with adverse changes in brain morphology, which accelerates cognitive aging and later dementia risk. Clear evidence is lacking, however, regarding whether inflammation relates to cognition in midlife via changes in brain morphology. Accordingly, the current study examines whether associations of inflammation with cognitive function are mediated by variation in cortical gray matter volume among midlife adults. Methods Plasma levels of interleukin (IL)-6 and C-reactive protein (CRP), relatively stable markers of peripheral systemic inflammation, were assessed in 408 community volunteers aged 30–54 years. All participants underwent structural neuroimaging to assess global and regional brain morphology and completed neuropsychological tests sensitive to early changes in cognitive function. Measurements of brain morphology (regional tissue volumes and cortical thickness and surface area) were derived using Freesurfer. Results Higher peripheral inflammation was associated with poorer spatial reasoning, short term memory, verbal proficiency, learning and memory, and executive function, as well as lower cortical gray and white matter volumes, hippocampal volume and cortical surface area. Mediation models with age, sex and intracranial volume as covariates showed cortical gray matter volume to partially mediate the association of inflammation with cognitive performance. Exploratory analyses of body mass suggested that adiposity may be a source of the inflammation linking brain morphology to cognition. Conclusions Inflammation and adiposity might relate to cognitive decline via influences on brain morphology. PMID:25882911
Wu, Yu-Tzu
2017-01-01
Background Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people. Methods and findings We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011–2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors—cognitive and social activity, physical activity, diet, alcohol consumption, and smoking—and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%–23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%–27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve. Conclusions Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health may be supported by a healthy and active lifestyle, in later life. PMID:28323829
Linking Biological and Cognitive Aging: Toward Improving Characterizations of Developmental Time
DeCarlo, Correne A.; Dixon, Roger A.
2011-01-01
Objectives. Chronological age is the most frequently employed predictor in life-span developmental research, despite repeated assertions that it is best conceived as a proxy for true mechanistic changes that influence cognition across time. The present investigation explores the potential that selected functional biomarkers may contribute to the more effective conceptual and operational definitions of developmental time. Methods. We used data from the Victoria Longitudinal Study to explore both static and dynamic biological or physiological markers that arguably influence process-specific mechanisms underlying cognitive changes in late life. Multilevel models were fit to test the dynamic coupling between change in theoretically relevant biomarkers (e.g., grip strength, pulmonary function) and change in select cognitive measures (e.g., executive function, episodic and semantic memory). Results. Results showed that, independent of the passage of developmental time (indexed as years in study), significant time-varying covariation was observed linking corresponding declines for select cognitive outcomes and biological markers. Discussion. Our findings support the interpretation that cognitive decline is not due to chronological aging per se but rather reflects multiple causal factors from a broad range of biological and physical health domains that operate along the age continuum. PMID:21743053
Optimizing Functional Network Representation of Multivariate Time Series
NASA Astrophysics Data System (ADS)
Zanin, Massimiliano; Sousa, Pedro; Papo, David; Bajo, Ricardo; García-Prieto, Juan; Pozo, Francisco Del; Menasalvas, Ernestina; Boccaletti, Stefano
2012-09-01
By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks.
Optimizing Functional Network Representation of Multivariate Time Series
Zanin, Massimiliano; Sousa, Pedro; Papo, David; Bajo, Ricardo; García-Prieto, Juan; Pozo, Francisco del; Menasalvas, Ernestina; Boccaletti, Stefano
2012-01-01
By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks. PMID:22953051
Erickson, Kirk I.; Kim, Jennifer S.; Suever, Barbara L.; Voss, Michelle W.; Francis, B. Magnus; Kramer, Arthur F.
2008-01-01
Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age. PMID:18958211
Cognitively Stimulating Leisure Activity and Subsequent Cognitive Function: A SHARE-based Analysis.
Litwin, Howard; Schwartz, Ella; Damri, Noam
2017-10-01
The aim of the inquiry was to examine whether cognitively stimulating leisure activity (CSLA) can delay or reduce cognitive decline in late life and whether its effect is moderated by education, age, or activity pattern. Employing secondary analysis of data on respondents aged 65 and older from the 4th and 5th waves of the Survey of Health, Ageing and Retirement in Europe (N = 16,572), the inquiry regressed cognitive function (memory, numeracy, and fluency) at Time 2 on frequency of engagement in CSLA at baseline, controlling for cognitive function scores at baseline and a range of confounders. The study also considered education by CSLA and age by CSLA interactions, as well as the effect of CSLA patterns. CSLA frequency was found to be positively related to subsequent cognitive functioning on all measures, 2 years later. The effect of CSLA on memory and fluency was stronger among those with lower education, whereas the age by CSLA interaction was not significant. Respondents who started CSLA after baseline showed better cognitive functioning at Time 2 than those who did not engage in CSLA at all and those who had engaged in such activity at baseline but stopped. The study documents that CSLAs constitute a potential source for the delay or reduction of cognitive decline, regardless of one's age. As such, practitioners should recognize the value of this medium and encourage its greater use in appropriate settings. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Ullmann, Gerhild; Williams, Harriet G
2016-07-01
Poor cognitive health a major concern of aging individuals, can compromise independent living. More than 16 million people in the United States are affected by cognitive impairment. We have studied the effects of the Feldenkrais Method(®) on cognitive function. In this case series with three participants cognitive function was assessed with the Trail Making Test A and B at baseline and after the Feldenkrais intervention. All participants improved performance on Trail Making Test A and B after completing the Feldenkrais intervention indicating that Feldenkrais lessons may offset age-related decline in cognitive function. The results of this case series warrant larger scale studies on cognitive outcomes of Feldenkrais interventions in clinical and non-clinical populations. Copyright © 2015 Elsevier Ltd. All rights reserved.
Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline.
Yurko-Mauro, Karin; McCarthy, Deanna; Rom, Dror; Nelson, Edward B; Ryan, Alan S; Blackwell, Andrew; Salem, Norman; Stedman, Mary
2010-11-01
Docosahexaenoic acid (DHA) plays an important role in neural function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly adults and in patients with Alzheimer's disease. Higher DHA intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in age-related cognitive decline (ARCD) have not been fully examined. Determine effects of DHA administration on improving cognitive functions in healthy older adults with ARCD. Randomized, double-blind, placebo-controlled, clinical study was conducted at 19 U.S. clinical sites. A total of 485 healthy subjects, aged ≥55 with Mini-Mental State Examination >26 and a Logical Memory (Wechsler Memory Scale III) baseline score ≥1 standard deviation below younger adults, were randomly assigned to 900 mg/d of DHA orally or matching placebo for 24 weeks. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Intention-to-treat analysis demonstrated significantly fewer PAL six pattern errors with DHA versus placebo at 24 weeks (difference score, -1.63 ± 0.76 [-3.1, -0.14, 95% CI], P = .03). DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests. Plasma DHA levels doubled and correlated with improved PAL scores (P < .02) in the DHA group. DHA was well tolerated with no reported treatment-related serious adverse events. Twenty-four week supplementation with 900 mg/d DHA improved learning and memory function in ARCD and is a beneficial supplement that supports cognitive health with aging. Clinicaltrials.gov, Identifier: NCT0027813. Copyright © 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Avidan, Michael S; FCASA; Searleman, Adam C; Storandt, Martha; Barnett, Kara; Vannucci, Andrea; Saager, Leif; Xiong, Chengjie; Grant, Elizabeth A; Kaiser, Dagmar; Morris, John C; Evers, Alex S
2009-01-01
Background Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer's disease to overcome some limitations. Methods In this retrospective cohort study, three groups were identified from participants tested annually at Washington University's Alzheimer Disease Research Center in St. Louis: those with non-cardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Results Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common following surgery or illness. Conclusions The study did not detect long-term cognitive decline independently attributable to surgery or illness nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer's disease, may presently be made without factoring in the specter of persistent cognitive deterioration. PMID:19786858
Avidan, Michael S; Searleman, Adam C; Storandt, Martha; Barnett, Kara; Vannucci, Andrea; Saager, Leif; Xiong, Chengjie; Grant, Elizabeth A; Kaiser, Dagmar; Morris, John C; Evers, Alex S
2009-11-01
Persistent postoperative cognitive decline is thought to be a public health problem, but its severity may have been overestimated because of limitations in statistical methodology. This study assessed whether long-term cognitive decline occurred after surgery or illness by using an innovative approach and including participants with early Alzheimer disease to overcome some limitations. In this retrospective cohort study, three groups were identified from participants tested annually at the Washington University Alzheimer's Disease Research Center in St. Louis, Missouri: those with noncardiac surgery, illness, or neither. This enabled long-term tracking of cognitive function before and after surgery and illness. The effect of surgery and illness on longitudinal cognitive course was analyzed using a general linear mixed effects model. For participants without initial dementia, time to dementia onset was analyzed using sequential Cox proportional hazards regression. Of the 575 participants, 214 were nondemented and 361 had very mild or mild dementia at enrollment. Cognitive trajectories did not differ among the three groups (surgery, illness, control), although demented participants declined more markedly than nondemented participants. Of the initially nondemented participants, 23% progressed to a clinical dementia rating greater than zero, but this was not more common after surgery or illness. The study did not detect long-term cognitive decline independently attributable to surgery or illness, nor were these events associated with accelerated progression to dementia. The decision to proceed with surgery in elderly people, including those with early Alzheimer disease, may be made without factoring in the specter of persistent cognitive deterioration.
Henneges, Carsten; Reed, Catherine; Chen, Yun-Fei; Dell'Agnello, Grazia; Lebrec, Jeremie
2016-01-01
Improved understanding of the pattern of cognitive decline in Alzheimer's disease (AD) would be useful to assist primary care physicians in explaining AD progression to patients and caregivers. To identify the sequence in which cognitive abilities decline in community-dwelling patients with AD. Baseline data were analyzed from 1,495 patients diagnosed with probable AD and a Mini-Mental State Examination (MMSE) score ≤ 26 enrolled in the 18-month observational GERAS study. Proportional odds logistic regression models were applied to model MMSE subscores (orientation, registration, attention and concentration, recall, language, and drawing) and the corresponding subscores of the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), using MMSE total score as the index of disease progression. Probabilities of impairment start and full impairment were estimated at each MMSE total score level. From the estimated probabilities for each MMSE subscore as a function of the MMSE total score, the first aspect of cognition to start being impaired was recall, followed by orientation in time, attention and concentration, orientation in place, language, drawing, and registration. For full impairment in subscores, the sequence was recall, drawing, attention and concentration, orientation in time, orientation in place, registration, and language. The sequence of cognitive decline for the corresponding ADAS-cog subscores was remarkably consistent with this pattern. The sequence of cognitive decline in AD can be visualized in an animation using probability estimates for key aspects of cognition. This might be useful for clinicians to set expectations on disease progression for patients and caregivers.
The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain
Mather, Mara; Harley, Carolyn W.
2016-01-01
Research on cognitive aging has focused on how decline in various cortical and hippocampal regions influence cognition. However, brainstem regions play essential modulatory roles, and new evidence suggests that among these, the integrity of the locus coeruleus-norepinephrine system plays a key role in determining late life cognitive abilities. The locus coeruleus is especially vulnerable to toxins and infection and is often the first place Alzheimer’s related pathology appears, with most people showing at least some tau pathology by their mid-twenties. On the other hand, norepinephrine released from the locus coeruleus during arousing, mentally challenging or novel situations helps protect neurons from damage, which may help explain how education and engaging careers prevent cognitive decline in later years. PMID:26895736
Electrophysiologic Assessment of Auditory Training Benefits in Older Adults
Anderson, Samira; Jenkins, Kimberly
2015-01-01
Older adults often exhibit speech perception deficits in difficult listening environments. At present, hearing aids or cochlear implants are the main options for therapeutic remediation; however, they only address audibility and do not compensate for central processing changes that may accompany aging and hearing loss or declines in cognitive function. It is unknown whether long-term hearing aid or cochlear implant use can restore changes in central encoding of temporal and spectral components of speech or improve cognitive function. Therefore, consideration should be given to auditory/cognitive training that targets auditory processing and cognitive declines, taking advantage of the plastic nature of the central auditory system. The demonstration of treatment efficacy is an important component of any training strategy. Electrophysiologic measures can be used to assess training-related benefits. This article will review the evidence for neuroplasticity in the auditory system and the use of evoked potentials to document treatment efficacy. PMID:27587912
Aging effects on functional auditory and visual processing using fMRI with variable sensory loading.
Cliff, Michael; Joyce, Dan W; Lamar, Melissa; Dannhauser, Thomas; Tracy, Derek K; Shergill, Sukhwinder S
2013-05-01
Traditionally, studies investigating the functional implications of age-related structural brain alterations have focused on higher cognitive processes; by increasing stimulus load, these studies assess behavioral and neurophysiological performance. In order to understand age-related changes in these higher cognitive processes, it is crucial to examine changes in visual and auditory processes that are the gateways to higher cognitive functions. This study provides evidence for age-related functional decline in visual and auditory processing, and regional alterations in functional brain processing, using non-invasive neuroimaging. Using functional magnetic resonance imaging (fMRI), younger (n=11; mean age=31) and older (n=10; mean age=68) adults were imaged while observing flashing checkerboard images (passive visual stimuli) and hearing word lists (passive auditory stimuli) across varying stimuli presentation rates. Younger adults showed greater overall levels of temporal and occipital cortical activation than older adults for both auditory and visual stimuli. The relative change in activity as a function of stimulus presentation rate showed differences between young and older participants. In visual cortex, the older group showed a decrease in fMRI blood oxygen level dependent (BOLD) signal magnitude as stimulus frequency increased, whereas the younger group showed a linear increase. In auditory cortex, the younger group showed a relative increase as a function of word presentation rate, while older participants showed a relatively stable magnitude of fMRI BOLD response across all rates. When analyzing participants across all ages, only the auditory cortical activation showed a continuous, monotonically decreasing BOLD signal magnitude as a function of age. Our preliminary findings show an age-related decline in demand-related, passive early sensory processing. As stimulus demand increases, visual and auditory cortex do not show increases in activity in older compared to younger people. This may negatively impact on the fidelity of information available to higher cognitive processing. Such evidence may inform future studies focused on cognitive decline in aging. Copyright © 2012 Elsevier Ltd. All rights reserved.
Buchman, Aron S.; Boyle, Patricia A.; Leurgans, Sue E.; Barnes, Lisa L.; Bennett, David A.
2010-01-01
Objective To examine the association of cognitive function with the risk of incident mobility impairments and the rate of declining mobility in older adults. Design Prospective, observational cohort study. Setting Retirement communities across metropolitan Chicago. Participants 1154 ambulatory elders from two longitudinal studies without baseline clinical dementia or history of stroke or Parkinson’s disease. Measurements All participants underwent baseline cognitive testing and annual mobility exams. Mobility impairments were based on annual timed walking performance. A composite mobility measure which summarized gait and balance measures was used to examine the annual rate of mobility change. Results During follow-up of 4.5 years, 423 of 836 (50.6%) participants developed impaired mobility. In a proportional hazards model controlled for age, sex, education and race, each 1-unit higher level of baseline global cognition was associated with a reduction to about half in the risk of mobility impairments (HR=0.51, 95% CI 0.40, 0.66) and was similar to a participant being about 13 years younger at baseline. These results did not vary by sex or race and were unchanged in analyses controlling for BMI, physical activity, vascular diseases and risk factors. The level of cognition in 5 different cognitive abilities was also related to incident mobility impairment. Cognition showed similar associations with incident loss of the ability to ambulate. Linear mixed-effects models showed that global cognition at baseline was associated with the rate of declining mobility. Conclusions Among ambulatory elders, cognition is associated with incident mobility impairment and mobility decline. PMID:21606900
Brodaty, Henry; Aerts, Liesbeth; Crawford, John D; Heffernan, Megan; Kochan, Nicole A; Reppermund, Simone; Kang, Kristan; Maston, Kate; Draper, Brian; Trollor, Julian N; Sachdev, Perminder S
2017-05-01
Mild cognitive impairment (MCI) is considered an intermediate stage between normal aging and dementia. It is diagnosed in the presence of subjective cognitive decline and objective cognitive impairment without significant functional impairment, although there are no standard operationalizations for each of these criteria. The objective of this study is to determine which operationalization of the MCI criteria is most accurate at predicting dementia. Six-year longitudinal study, part of the Sydney Memory and Ageing Study. Community-based. 873 community-dwelling dementia-free adults between 70 and 90 years of age. Persons from a non-English speaking background were excluded. Seven different operationalizations for subjective cognitive decline and eight measures of objective cognitive impairment (resulting in 56 different MCI operational algorithms) were applied. The accuracy of each algorithm to predict progression to dementia over 6 years was examined for 618 individuals. Baseline MCI prevalence varied between 0.4% and 30.2% and dementia conversion between 15.9% and 61.9% across different algorithms. The predictive accuracy for progression to dementia was poor. The highest accuracy was achieved based on objective cognitive impairment alone. Inclusion of subjective cognitive decline or mild functional impairment did not improve dementia prediction accuracy. Not MCI, but objective cognitive impairment alone, is the best predictor for progression to dementia in a community sample. Nevertheless, clinical assessment procedures need to be refined to improve the identification of pre-dementia individuals. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
Eguchi, Yoko; Tasato, Kumiko; Nakajima, Shinichiro; Noda, Yoshihiro; Tsugawa, Sakiko; Shinagawa, Shunichiro; Niimura, Hidehito; Hirose, Nobuyoshi; Arai, Yasumichi; Mimura, Masaru
2018-03-07
Despite a steady increase in life expectancy, a few studies have investigated cross-sectional correlates and longitudinal predictors of cognitive function, a core domain of the successful aging, among socio-clinico-demographic factors in the oldest-old exclusively. The aims of this study were to examine socio-clinico-demographic characteristics associated with global cognition and its changes in the oldest-old. We reanalyzed a dataset of cognitively preserved community-dwelling subjects aged 85 years and older in the Tokyo Oldest Old Survey on Total Health, a 6-year longitudinal observational study. This study consisted of (1) baseline cross-sectional analyses examining correlates of global cognition (n = 248) among socio-clinico-demographic factors and (2) longitudinal analyses examining baseline predictors for changes of global cognition in 3-year follow-up (n = 195). The Mini-Mental State Examination was used as a screening test to assess global cognition. At baseline, higher weights were related to higher cognitive function in the oldest-old. The baseline predictors of global cognitive decline in 3-year follow-up were higher global cognition, shorter education period, and lower sociocultural activities and lower instrumental activity of daily living, in this order. The present study suggests that it is crucial to attain higher education during early life and avoid leanness or obesity, participate in sociocultural cognitive activities during late life, and maintain instrumental activity of daily living to preserve optimal cognitive function in the oldest-old, which will facilitate developing prevention strategies for cognitive decline and promoting successful aging in this increasing population. Copyright © 2018 John Wiley & Sons, Ltd.
Cognitive decline and slower reaction time in elderly individuals with mild cognitive impairment.
Chen, Ko-Chia; Weng, Chia-Ying; Hsiao, Sigmund; Tsao, Wen-Long; Koo, Malcolm
2017-11-01
The relationship between declining performance, as measured by changes in reaction time, and declining cognitive function has not been critically studied. The aim of the present study was to investigate the association between reaction time during a task and cognitive ability in elderly Taiwanese individuals. Patients aged 65 years or older with mild cognitive impairment (MCI) (n = 33) and Alzheimer's disease (n = 26) were recruited from the neurology clinic of a regional hospital in southern Taiwan. In addition, 28 healthy controls aged 65 years or older were recruited from the community. The cognitive performance of the study participants was assessed using the Cognitive Abilities Screening Instrument (CASI). A computer-administered simple reaction time (SRT) task and a flanker reaction time (FRT) task were administered to assess participants' cognitive function. A non-parametric Kruskal-Wallis test was performed to compare CASI scores, SRT, and FRT among the three groups. anova was also used to compare CASI scores, inverse-transformed SRT, and inverse-transformed FRT among the three groups, with adjustment for age and years of education. Additionally, Pearson's partial correlation coefficients were used to assess the association of CASI scores with inverse-transformed SRT, and inverse-transformed FRT within each of the three groups. Significant differences in CASI scores, SRT, and FRT were found between the Alzheimer's disease group and the other two groups, either with or without adjustment for age or education. The reaction time of patients with Alzheimer's disease was significantly slower than the other two groups. Moreover, significant correlation between CASI and FRT was found in patients with MCI. Altered performance in a speed task was observed in patients with MCI. The FRT task should further be explored for its role as a marker for cognitive decline in elderly individuals, particularly in those with MCI. © 2017 Japanese Psychogeriatric Society.
Lifestyle-related factors in predementia and dementia syndromes.
Solfrizzi, Vincenzo; Capurso, Cristiano; D'Introno, Alessia; Colacicco, Anna Maria; Santamato, Andrea; Ranieri, Maurizio; Fiore, Pietro; Capurso, Antonio; Panza, Francesco
2008-01-01
Cognitive decline and dementia have a deep impact on the health and quality of life of older subjects and their caregivers. Since the therapeutic options currently available have demonstrated limited efficacy, the search for preventive strategies for cognitive decline and dementia are mandatory. A possible role of lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes and the cognitive decline of degenerative (Alzheimer's disease [AD]) or vascular origin. At present, cumulative evidence suggests that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia and AD. Moderate alcohol drinking has been proposed as a protective factor against MCI and dementia in several longitudinal studies, but contrasting findings also exist. The Mediterranean diet could therefore be an interesting model with which to further study the association between dietary patterns and cognitive functioning, given the suggested role of many components of this diet (monounsaturated fatty acids, polyunsaturated fatty acids, cereals and red wine) in contrasting cognitive impairment and dementia. The association between low education and predementia and dementia syndromes is supported by the majority of studies, but very few studies have investigated whether this association may be attributed with lifestyle factors that covary with education. Studies in the literature seem to identify in physical exercise one promising strategy in decreasing cognitive decline, but some of the limitations of these studies do not allow us to draw definite conclusions. At present, in older subjects, healthy diets, antioxidant supplements, the prevention of nutritional deficiencies, and moderate physical activity could be considered the first line of defense against the development and progression of predementia and dementia syndromes. However, in most cases, these were only observational studies, and results are awaited from large multicenter randomized clinical trials in older persons that may clarify the possible synergy, for example, between moderate exercise, physical activity and healthy Mediterranean diet on cognition in the elderly.
Anderson-Mooney, Amelia J; Schmitt, Frederick A; Head, Elizabeth; Lott, Ira T; Heilman, Kenneth M
2016-04-01
Down syndrome (DS) is the most common genetic cause of intellectual disability in children. With aging, DS is associated with an increased risk for Alzheimer's disease (AD). The development of AD neuropathology in individuals with DS can result in further disturbances in cognition and behavior and may significantly exacerbate caregiver burden. Early detection may allow for appropriate preparation by caregivers. Recent literature suggests that declines in gait may serve as an early marker of AD-related cognitive disorders; however, this relationship has not been examined in individuals with DS. The theory regarding gait dyspraxia and cognitive decline in the general population is reviewed, and potential applications to the population with individuals with DS are highlighted. Challenges and benefits in the line of inquiry are discussed. In particular, it appears that gait declines in aging individuals with DS may be associated with known declines in frontoparietal gray matter, development of AD-related pathology, and white matter losses in tracts critical to motor control. These changes are also potentially related to the cognitive and functional changes often observed during the same chronological period as gait declines in adults with DS. Gait declines may be an early marker of cognitive change, related to the development of underlying AD-related pathology, in individuals with DS. Future investigations in this area may provide insight into the clinical changes associated with development of AD pathology in both the population with DS and the general population, enhancing efforts for optimal patient and caregiver support and propelling investigations regarding safety/quality of life interventions and disease-modifying interventions. Copyright © 2016 Elsevier Inc. All rights reserved.
Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.
Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad
2016-01-01
Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.
Alfaro, Freddy J; Gavrieli, Anna; Saade-Lemus, Patricia; Lioutas, Vasileios-Arsenios; Upadhyay, Jagriti; Novak, Vera
2018-01-01
Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.
Impact of Education on Memory Deficits in Subclinical Depression.
McLaren, Molly E; Szymkowicz, Sarah M; Kirton, Joshua W; Dotson, Vonetta M
2015-08-01
Elevated depressive symptoms are associated with cognitive deficits, while higher education protects against cognitive decline. This study was conducted to test if education level moderates the relationship between depressive symptoms and cognitive function. Seventy-three healthy, dementia-free adults aged 18-81 completed neuropsychological tests, as well as depression and anxiety questionnaires. Controlling for age, sex, and state anxiety, we found a significant interaction of depressive symptoms and education for immediate and delayed verbal memory, such that those with a higher education level performed well regardless of depressive symptomatology, whereas those with lower education and high depressive symptoms had worse performance. No effects were found for executive functioning or processing speed. Results suggest that education protects against verbal memory deficits in individuals with elevated depressive symptoms. Further research on cognitive reserve in depression-related cognitive deficits and decline is needed to understand the mechanisms behind this phenomenon. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
The Association between the Mediterranean Dietary Pattern and Cognitive Health: A Systematic Review
Wright, Olivia R. L.
2017-01-01
The ageing population is accompanied by increased rates of cognitive decline and dementia. Not only does cognitive decline have a profound impact on an individual’s health and quality of life, but also on that of their caregivers. The Mediterranean diet (MD) has been known to aid in reducing the risk of cardiovascular diseases, cancer and diabetes. It has been recently linked to better cognitive function in the elderly population. The purpose of this review was to compile evidence based data that examined the effect of adherence to the MD on cognitive function and the risk of developing dementia or Alzheimer’s disease. This review followed PRISMA guidelines and was conducted using four databases and resulted in 31 articles of interest. Cross-sectional studies and cohort studies in the non-Mediterranean region showed mixed results. However, cohort studies in the Mediterranean region and randomized controlled trials showed more cohesive outcomes of the beneficial effect of the MD on cognitive function. Although more standardized and in-depth studies are needed to strengthen the existing body of evidence, results from this review indicate that the Mediterranean diet could play a major role in cognitive health and risk of Alzheimer’s disease and dementia. PMID:28657600
Locascio, Joseph J.; Fukumoto, Hiroaki; Yap, Liang; Bottiglieri, Teodoro; Growdon, John H.; Hyman, Bradley T.; Irizarry, Michael C.
2008-01-01
Objective To examine whether plasma markers of amyloid precursor protein metabolism (amyloid β-protein ending in Val-40 [Aβ40] and Ala-42 [Aβ42]), inflammation (high-sensitivity C-reactive protein), and folic acid metabolism (folic acid, vitamin B12, and total homocysteine levels) are associated with the rate of cognitive and functional decline in persons with Alzheimer disease. Design Longitudinal study across a mean (SD) of 4.2 (2.6) years with assessments at approximately 6- to 12- month intervals. Setting Out patient care. Patients A cohort of 122 patients having a clinical diagnosis of probable Alzheimer disease, each with at least 2 assessments across time. Main Outcome Measures Scores on the cognitive Information-Memory-Concentration subscale of the Blessed Dementia Scale and the functional Weintraub Activities of Daily Living Scale. Results Low plasma levels of Aβ40, Aβ42, and high-sensitivity C-reactive protein were associated with a significantly more rapid cognitive decline, as indexed using the Blessed Dementia Scale, than were high levels. Low levels of Aβ42 and high-sensitivity C-reactive protein were significantly associated with more rapid functional decline on the Weintraub Activities of Daily Living Scale than were high levels. These plasma markers contributed about 5% to 12% of the variance accounted for on the Blessed Dementia Scale and the Activities of Daily Living Scale by fixed-effects predictors. Measures of folic acid metabolism were not associated with changes on either the Blessed Dementia Scale or the Activities of Daily Living Scale. Conclusions Plasma markers of amyloid precursor protein metabolism and C-reactive protein may be associated with the rate of cognitive and functional decline in patients with Alzheimer disease. PMID:18541797
Torniainen-Holm, Minna; Suvisaari, Jaana; Lindgren, Maija; Härkänen, Tommi; Dickerson, Faith; Yolken, Robert H
2018-03-01
Earlier studies have documented an association between cytomegalovirus and cognitive impairment, but results have been inconsistent. Few studies have investigated the association of cytomegalovirus and Epstein-Barr virus with cognitive decline longitudinally. Our aim was to examine whether cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in adults. The study sample is from the Finnish Health 2000 Survey (BRIF8901, n = 7112), which is representative of the Finnish adult population. The sample was followed up after 11 years in the Health 2011 Survey. In addition, persons with dementia were identified from healthcare registers. In the Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%. Seropositivity of the viruses and antibody levels were mostly not associated with cognitive performance. In the middle-aged adult group, cytomegalovirus serointensity was associated with impaired performance in verbal learning. However, the association disappeared when corrected for multiple testing. No interactions between infection and time or between the two infections were significant when corrected for multiple testing. Seropositivity did not predict dementia diagnosis. The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level. Copyright © 2018. Published by Elsevier Inc.
Diniz, Breno Satler; Reynolds, Charles F.; Begley, Amy; Dew, Mary Amanda; Anderson, Stewart J.; Lotrich, Francis; Erickson, Kirk I.; Lopez, Oscar; Aizenstein, Howard; Sibille, Etienne L.; Butters, Meryl A.
2014-01-01
Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD+MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD+NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function). We included 160 elderly participants in this study (72 LLD+NCD, 55 LLD+MCI and 33 never-depressed cognitively normal elderly participants). At the same visits, cognitive assessments were conducted and blood sampling to determine serum BDNF levels were collected at baseline assessment and after one and two years of follow-up. We utilized repeated measure, mixed effect models to assess: (1) the effects of diagnosis (LLD+MCI, LLD+NCD, and controls), time, and their interaction on BDNF levels; and (2) the effects of donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD+MCI vs. LLD+NCD), and interactions between these contrasts on BDNF levels. We found a significant effect of time on BDNF level (p=0.02) and a significant decline in BDNF levels over 2 years of follow-up in participants with LLD+MCI (p=0.004) and controls (p=0.04). We found no effect of donepezil treatment on BDNF level. The present results suggest that aging is an important factor related to decline in BDNF level. PMID:24290367
Roy, Cindy N.
2010-01-01
Synopsis While anemia is regarded as a relatively common occurrence in older adults, the vigor with which the medical community should intervene to correct this common problem is disputed. Epidemiologic data clearly correlate anemia with functional decline, disability and mortality. Anemia may contribute to functional decline by restricting oxygen delivery to muscle, or to cognitive decline by restricting oxygen delivery to the brain. On the other hand, the erythron may be a separate target of the same biological mediators that influence deterioration of physiologic systems that contribute to weakness, functional and cognitive decline and mortality. Clinical trials aimed to treat anemia in older adults could assess whether physical performance is improved or whether mortality risk declines with improved hemoglobin, but sufficient evidence from such trials is currently lacking. With few guidelines regarding treatment for older adults and significant risk for adverse events associated with transfusion and erythroid stimulating agents (ESA), anemia often goes untreated or ignored in geriatric clinics. This article reviews the problem of anemia in older adults, with a particular emphasis on the frail elderly. We will review the gaps in our evidence base for the treatment of anemia in older adults and assess options for advancing the field. PMID:21093723
Martin, Magali Saint; Sforza, Emilia; Roche, Frédéric; Barthélémy, Jean Claude; Thomas-Anterion, Catherine
2015-02-01
Sleep breathing disorder (SBD) may be an important factor in age-related cognitive decline. In a cohort of healthy elderly subjects, we performed an 8-y longitudinal study to assess whether changes in cognitive function occur in untreated elderly patients with SBD and without dementia and the factors implicated in these changes. A population-based longitudinal study. Clinical research settings. A total of 559 participants of the PROOF study aged 67 y at the study entry and free from neurological disorders were examined. N/A. Abnormal breathing events were defined by an apnea-hypopnea index (AHI) > 15. The raw cognitive data and averaged Z-scores for the attentional, executive, and memory functions were collected at the baseline and follow-up. At baseline, AHI > 15 was found in 54% of subjects with 18% having an AHI > 30. At follow-up, the presence of abnormal breathing events was associated with a slight but significant decline in the attentional domain (P = 0.01), which was more evident in the subjects with an AHI > 30 (P = 0.004). No significant changes over time were observed in the executive and memory functions. Several indices of chronic hypoxemia, defined either as a cumulative peripheral oxygen saturation (SpO2) < 90% or a minimal SpO2, accounted for portions of the variance in the decline in attention. All observed effects were small, accounting for 4-7% of variance in multivariate models. In healthy elderly subjects, various components of sleep breathing disorder at baseline were associated with small changes in selected cognitive functions specific to the attention domain after controlling for multiple comorbidities, such as sleepiness, hypertension, diabetes, anxiety, and depression. ClinicalTrials.gov identifiers NCT 00759304 and NCT 00766584. © 2015 Associated Professional Sleep Societies, LLC.
Liang, Chih-Kuang; Chou, Ming-Yueh; Chen, Liang-Yu; Wang, Kuei-Yu; Lin, Shih-Yi; Chen, Liang-Kung; Lin, Yu-Te; Liu, Tsung-Yun; Loh, Ching-Hui
2017-04-01
To develop experimental multi-domain interventions for older people with mild-to-moderate dementia, and to evaluate the effect of delaying cognitive and physical decline, and improvement or prevention of geriatric syndromes during 1-year follow up. Participants aged 65 years and older with mild-to-moderate dementia (clinical dementia rating [CDR] 1 or 2) were grouped as intervention in Jia-Li Veterans Home and usual care model in the community (Memory clinic). All residents in Jia-Li Veterans Home received comprehensive intervention, including Multi-disciplinary team consultation and intervention, Multi-component non-pharmacological management, geriatric syndromes survey and intervention by CGA, and a dementia friendly medical Green channel Approach (2MCGA). The decline of cognitive and physical function are determined by the change of Mini-Mental State Examination score, CDR and the sum of CDR box, as well as activities of daily living based on the Barthel Index. We also screened geriatric syndromes at baseline and 1 year later. Participants in the intervention group were older and had a lower educational level, lower body mass index, poor baseline activities of daily living function, lower visual impairment, and higher rates of hearing impairment, polypharmacy and risk of malnutrition. The residents receiving 2MCGA had lower baseline Mini-Mental State Examination scores, and higher CDR. For residents in Jia-Li Veterans Home, all cognitive measurements except Mini-Mental State Examination were significantly associated with delaying the decline of cognition after analyzing by multiple linear regression, and multivariate logistic regression also showed that patients living in the community was independently associated with a higher odds ratio for activities of daily living decline (3.180, 95% CI 1.384-7.308, P = 0.006). There are also more improvement in their baseline geriatric syndromes and suffered less from new geriatric syndromes, including falls, urinary incontinence, and risk of malnutrition. The 2MCGA intervention shows strong delays in the decline of cognition and physical function for older residents with mild-to-moderate dementia. Furthermore, this strategy can also improve or prevent the onset of new geriatric syndromes, especially fall episodes, urinary incontinence and risk of malnutrition. Geriatr Gerontol Int 2017; 17 (Suppl. 1): 36-43. © 2017 Japan Geriatrics Society.
O'Farrell, Erin; Smith, Andra; Collins, Barbara
2017-10-01
Studies to date have found little correlation between subjective and objective measures of cognitive function in cancer patients, making it difficult to interpret the significance of their cognitive complaints. The purpose of this study was to determine if a stronger correlation would be obtained using measures of cognitive change rather than static scores. Sixty women with early stage breast cancer underwent repeated cognitive assessment over the course of chemotherapy with a neuropsychological test battery (objective measure) and with the FACT-Cog (subjective measure). Their results were compared to 60 healthy women matched on age and education and assessed at similar intervals. We used multilevel modeling, with FACT-Cog as the dependent measure and ordinary least squares slopes of a neuropsychological summary score as the independent variable, to evaluate the co-variation between the subjective and objective measures over time RESULTS: Measures of both objective and subjective cognitive function declined over the course of chemotherapy in the breast cancer patients but there was no significant relationship between them, even when using change measures. Change in objective cognitive function was not related to change in anxiety or fatigue scores but the decline in perceived cognitive function was associated with greater anxiety and fatigue. The discrepancy in objective and subjective measures of cognition in breast cancer patients cannot be accounted for in terms of a failure to use change measures. Although the results are negative, we contend that this is the more appropriate methodology for analyzing cancer-related changes in cognition. Copyright © 2016 John Wiley & Sons, Ltd.
Wong, Adrian; Lau, Alexander Y. L.; Lo, Eugene; Tang, Michael; Wang, Zhaolu; Liu, Wenyan; Tanner, Nicole; Chau, Natalie; Law, Lorraine; Shi, Lin; Chu, Winnie C. W.; Yang, Jie; Xiong, Yun-yun; Lam, Bonnie Y. K.; Au, Lisa; Chan, Anne Y. Y.; Soo, Yannie; Leung, Thomas W. H.; Wong, Lawrence K. S.; Lam, Linda C. W.; Mok, Vincent C. T.
2016-01-01
Background Leisure activity participation has been shown to lower risks of cognitive decline in non-stroke populations. However, effects of leisure activities participation upon cognitive functions and risk of dementia after stroke are unclear. The purpose of this study is to examine the effects of recent past leisure activities participation upon cognitive functions and risk of incident dementia after stroke. Methods Hospital-based, retrospective cohort study. 88 of 1,013 patients with stroke or TIA having no prestroke dementia were diagnosed to have incident poststroke dementia (PSD) 3–6 months after stroke. Regular participation (≥3 times per week) in intellectual, recreational, social and physical activities over the year before the index stroke was retrospectively recorded at 3–6 months after stroke. Results Logistic regression analyses showed that regular participation in intellectual (RR 0.36, 95%CI 0.20–0.63) and stretching & toning physical exercise (0.37, 0.21–0.64) was significantly associated with a reduced risk of PSD after controlling for age, education, prestroke cognitive decline, stroke subtype, prior strokes and chronic brain changes including white matter changes, old infarcts and global atrophy. Results were similar in patients with past strokes in unadjusted models. Participation in increased number of activities in general (r = 0.41, p<0.01) and in intellectual (r = 0.40, p<0.01), recreational (r = 0.24, p<0.01), strenuous aerobic (r = 0.23, p<0.01) and mind-body (r = 0.10, p<0.01) activities was associated with higher poststroke Mini-mental State Examination scores in models adjusted for prestroke cognitive decline. Conclusions Regular participation in intellectual activities and stretching & toning exercise was associated with a significantly reduced short-term risk of PSD in patients with and without recurrent strokes. Participation in greater number of recent past leisure activities was associated with better poststroke cognitive performance. Findings of this retrospective cohort study call for studies of activity intervention for prevention of cognitive decline in individuals at elevated risk of stroke. PMID:27454124
Aging related cognitive changes associated with Alzheimer's disease in Down syndrome.
Firth, Nicholas C; Startin, Carla M; Hithersay, Rosalyn; Hamburg, Sarah; Wijeratne, Peter A; Mok, Kin Y; Hardy, John; Alexander, Daniel C; Strydom, André
2018-06-01
Individuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer's disease (AD), however, the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS. We applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals' disease stage. Decline in tests of memory, sustained attention/motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting that the model is valid. Our results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion into dementia, or postdiagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.
Vercambre, Marie-Noël; Boutron-Ruault, Marie-Christine; Ritchie, Karen; Clavel-Chapelon, Françoise; Berr, Claudine
2009-08-01
The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the 'Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale' (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline.
Negative Aspects of Close Relationships as Risk Factors for Cognitive Aging
Liao, Jing; Head, Jenny; Kumari, Meena; Stansfeld, Stephen; Kivimaki, Mika; Singh-Manoux, Archana; Brunner, Eric J.
2014-01-01
The extent to which social relationships influence cognitive aging is unclear. In this study, we investigated the association of midlife quality of close relationships with subsequent cognitive decline. Participants in the Whitehall II Study (n = 5,873; ages 45–69 years at first cognitive assessment) underwent executive function and memory tests 3 times over a period of 10 years (1997–1999 to 2007–2009). Midlife negative and positive aspects of close relationships were assessed twice using the Close Persons Questionnaire during the 8 years preceding cognitive assessment. Negative aspects of close relationships, but not positive aspects, were associated with accelerated cognitive aging. Participants in the top third of reported negative aspects of close relationships experienced a faster 10-year change in executive function (−0.04 standard deviation, 95% confidence interval: −0.08, −0.01) than those in the bottom third, which was comparable with 1 extra year of cognitive decline for participants aged 60 years after adjustment for sociodemographic and health status. Longitudinal analysis found no evidence of reverse causality. This study highlights the importance of differentiating aspects of social relationships to evaluate their unique associations with cognitive aging. PMID:25342204
Fliss, Rafika; Lemerre, Marion; Mollard, Audrey
2016-06-01
Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed.
Ramos-Miguel, Alfredo; Jones, Andrea A; Sawada, Ken; Barr, Alasdair M; Bayer, Thomas A; Falkai, Peter; Leurgans, Sue E; Schneider, Julie A; Bennett, David A; Honer, William G
2018-06-01
The molecular underpinnings associated with cognitive reserve remain poorly understood. Because animal models fail to fully recapitulate the complexity of human brain aging, postmortem studies from well-designed cohorts are crucial to unmask mechanisms conferring cognitive resistance against cumulative neuropathologies. We tested the hypothesis that functionality of the SNARE protein interactome might be an important resilience factor preserving cognitive abilities in old age. Cognition was assessed annually in participants from the Rush "Memory and Aging Project" (MAP), a community-dwelling cohort representative of the overall aging population. Associations between cognition and postmortem neurochemical data were evaluated in functional assays quantifying various species of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) machinery in samples from the inferior temporal (IT, n = 154) and middle-frontal (MF, n = 174) gyri. Using blue-native gel electrophoresis, we isolated and quantified several types of complexes containing the three SNARE proteins (syntaxin-1, SNAP25, VAMP), as well as the GABAergic/glutamatergic selectively expressed complexins-I/II (CPLX1/2), in brain tissue homogenates and reconstitution assays with recombinant proteins. Multivariate analyses revealed significant associations between IT and MF neurochemical data (SNARE proteins and/or complexes), and multiple age-related neuropathologies, as well as with multiple cognitive domains of MAP participants. Controlling for demographic variables, neuropathologic indices and total synapse density, we found that temporal 150-kDa SNARE species (representative of pan-synaptic functionality) and frontal CPLX1/CPLX2 ratio of 500-kDa heteromeric species (representative of inhibitory/excitatory input functionality) were, among all the immunocharacterized complexes, the strongest predictors of cognitive function nearest death. Interestingly, these two neurochemical variables were associated with different cognitive domains. In addition, linear mixed effect models of global cognitive decline estimated that both 150-kDa SNARE levels and CPLX1/CPLX2 ratio were associated with better cognition and less decline over time. The results are consistent with previous studies reporting that synapse dysfunction (i.e. dysplasticity) may be initiated early, and relatively independent of neuropathology-driven synapse loss. Frontotemporal dysregulation of the GABAergic/glutamatergic stimuli might be a target for future drug development. Copyright © 2018 Elsevier Inc. All rights reserved.
Liu, Dong; Pitta, Michael; Jiang, Haiyang; Lee, Jong-Hwan; Zhang, Guofeng; Chen, Xinzhi; Kawamoto, Elisa M.; Mattson, Mark P.
2012-01-01
Impaired brain energy metabolism and oxidative stress are implicated in cognitive decline and the pathological accumulations of amyloid β-peptide (Aβ) and hyperphosphorylated Tau (p-Tau) in Alzheimer's disease (AD). To determine whether improving brain energy metabolism will forestall disease progress in AD, the impact of the NAD+ precursor nicotinamide on brain cell mitochondrial function and macroautophagy, bioenergetics-related signaling and cognitive performance were studied in cultured neurons and in a mouse model of AD. Oxidative stress resulted in decreased mitochondrial mass, mitochondrial degeneration and autophagosome accumulation in neurons. Nicotinamide preserved mitochondrial integrity and autophagy function, and reduced neuronal vulnerability to oxidative/metabolic insults and Aβ toxicity. NAD+ biosynthesis, autophagy and PI3K signaling were required for the neuroprotective action of nicotinamide. Treatment of 3xTgAD mice with nicotinamide for 8 months resulted in improved cognitive performance, and reduced Aβ and p-Tau pathologies in hippocampus and cerebral cortex. Nicotinamide treatment preserved mitochondrial integrity, and improved autophagy-lysosome procession by enhancing lysosome/autolysosome acidification to reduce autophagosome accumulation. Treatment of 3xTgAD mice with nicotinamide resulted in elevated levels of activated neuroplasticity-related kinases (Akt and ERKs) and the transcription factor cyclic AMP response element-binding protein in the hippocampus and cerebral cortex. Thus, nicotinamide suppresses AD pathology and cognitive decline in a mouse model of AD by a mechanism involving improved brain bioenergetics with preserved functionality of mitochondria and the autophagy system. PMID:23273573
Berendsen, Agnes A M; Kang, Jae H; van de Rest, Ondine; Feskens, Edith J M; de Groot, Lisette C P G M; Grodstein, Francine
2017-05-01
To examine the association between long-term adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with cognitive function and decline in older American women. Prospective cohort study. The Nurses' Health Study, a cohort of registered nurses residing in 11 US states. A total of 16,144 women from the Nurses' Health Study, aged ≥70 years, who underwent cognitive testing a total of 4 times by telephone from 1995 to 2001 (baseline), with multiple dietary assessments between 1984 and the first cognitive examination. DASH adherence for each individual was based on scoring of intakes of 9 nutrient or food components. Long-term DASH adherence was calculated as the average DASH adherence score from up to 5 repeated measures of diet. Primary outcomes were cognitive function calculated as the average scores of the 4 repeated measures, as well as cognitive change of the Telephone Interview for Cognitive Status score and composite scores of global cognition and verbal memory. Greater adherence to long-term DASH score was associated with better average cognitive function, irrespective of apolipoprotein E ε4 allele status [multivariable-adjusted differences in mean z-scores between extreme DASH quintiles = 0.04 (95% confidence interval, CI 0.01-0.07), P trend = .009 for global cognition; 0.04 (95% CI 0.01-0.07), P trend = .002 for verbal memory and 0.16 (95% CI 0.03-0.29), and P trend = .03 for Telephone Interview for Cognitive Status, P interaction >0.24]. These differences were equivalent to being 1 year younger in age. Adherence to the DASH score was not associated with change in cognitive function over 6 years. Our findings in the largest cohort on dietary patterns and cognitive function to date indicate that long-term adherence to the DASH diet is important to maintain cognitive function at older ages. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.
Parbery-Clark, Alexandra; Strait, Dana L.; Anderson, Samira; Hittner, Emily; Kraus, Nina
2011-01-01
Much of our daily communication occurs in the presence of background noise, compromising our ability to hear. While understanding speech in noise is a challenge for everyone, it becomes increasingly difficult as we age. Although aging is generally accompanied by hearing loss, this perceptual decline cannot fully account for the difficulties experienced by older adults for hearing in noise. Decreased cognitive skills concurrent with reduced perceptual acuity are thought to contribute to the difficulty older adults experience understanding speech in noise. Given that musical experience positively impacts speech perception in noise in young adults (ages 18–30), we asked whether musical experience benefits an older cohort of musicians (ages 45–65), potentially offsetting the age-related decline in speech-in-noise perceptual abilities and associated cognitive function (i.e., working memory). Consistent with performance in young adults, older musicians demonstrated enhanced speech-in-noise perception relative to nonmusicians along with greater auditory, but not visual, working memory capacity. By demonstrating that speech-in-noise perception and related cognitive function are enhanced in older musicians, our results imply that musical training may reduce the impact of age-related auditory decline. PMID:21589653
Parbery-Clark, Alexandra; Strait, Dana L; Anderson, Samira; Hittner, Emily; Kraus, Nina
2011-05-11
Much of our daily communication occurs in the presence of background noise, compromising our ability to hear. While understanding speech in noise is a challenge for everyone, it becomes increasingly difficult as we age. Although aging is generally accompanied by hearing loss, this perceptual decline cannot fully account for the difficulties experienced by older adults for hearing in noise. Decreased cognitive skills concurrent with reduced perceptual acuity are thought to contribute to the difficulty older adults experience understanding speech in noise. Given that musical experience positively impacts speech perception in noise in young adults (ages 18-30), we asked whether musical experience benefits an older cohort of musicians (ages 45-65), potentially offsetting the age-related decline in speech-in-noise perceptual abilities and associated cognitive function (i.e., working memory). Consistent with performance in young adults, older musicians demonstrated enhanced speech-in-noise perception relative to nonmusicians along with greater auditory, but not visual, working memory capacity. By demonstrating that speech-in-noise perception and related cognitive function are enhanced in older musicians, our results imply that musical training may reduce the impact of age-related auditory decline.
USDA-ARS?s Scientific Manuscript database
The aging process often involves functional declines in cognition, leading to lower quality of life and increased need for care among older adults. Epidemiological evidence suggests that a diet rich in fruits and vegetables can reduce the risk of age-related cognitive impairment, in part due to the ...
The Effects of Sleep Deprivation on Item and Associative Recognition Memory
ERIC Educational Resources Information Center
Ratcliff, Roger; Van Dongen, Hans P. A.
2018-01-01
Sleep deprivation adversely affects the ability to perform cognitive tasks, but theories range from predicting an overall decline in cognitive functioning because of reduced stability in attentional networks to specific deficits in various cognitive domains or processes. We measured the effects of sleep deprivation on two memory tasks, item…
USDA-ARS?s Scientific Manuscript database
Docosahexaenoic acid (DHA) is a major constituent, and primary omega-3 fatty acid, in the brain. Evidence suggests that DHA consumption may promote cognitive functioning and prevent cognitive decline, and these effects may be particularly relevant in the context of fear or stress. However, the pot...
Alichniewicz, K. K.; Brunner, F.; Klünemann, H. H.; Greenlee, M. W.
2013-01-01
Performance on tasks that require saccadic inhibition declines with age and altered inhibitory functioning has also been reported in patients with Alzheimer's disease. Although mild cognitive impairment (MCI) is assumed to be a high-risk factor for conversion to AD, little is known about changes in saccadic inhibition and its neural correlates in this condition. Our study determined whether the neural activation associated with saccadic inhibition is altered in persons with amnestic mild cognitive impairment (aMCI). Functional magnetic resonance imaging (fMRI) revealed decreased activation in parietal lobe in healthy elderly persons compared to young persons and decreased activation in frontal eye fields in aMCI patients compared to healthy elderly persons during the execution of anti-saccades. These results illustrate that the decline in inhibitory functions is associated with impaired frontal activation in aMCI. This alteration in function might reflect early manifestations of AD and provide new insights in the neural activation changes that occur in pathological ageing. PMID:23898312
Acute Respiratory Distress Syndrome, Sepsis, and Cognitive Decline: A Review and Case Study
Jackson, James C.; Hopkins, Ramona O.; Miller, Russell R.; Gordon, Sharon M.; Wheeler, Arthur P.; Ely, E. Wesley
2013-01-01
The objective of this investigation is to review existing research pertaining to cognitive impairment and decline following critical illness and describe a case involving a 49-year-old female with sepsis and acute respiratory distress syndrome (ARDS) with no prior neurologic history who, compared to baseline neuropsychological test data, experienced dramatic cognitive decline and brain atrophy following treatment in the medical intensive care unit (ICU) at Vanderbilt University Medical Center. The patient participated in detailed clinical interviews and underwent comprehensive neuropsychological testing and neurological magnetic resonance imaging (MRI) at approximately 8 months and 3.5 years after ICU discharge. Compared to pre-ICU baseline test data, her intellectual function declined approximately 2 standard deviations from 139 to 106 (from the 99th to the 61st percentile) on a standardized intelligence test 8 months post-discharge, with little subsequent improvement. Initial diffusion tensor brain magnetic resonance imaging (DT-MRI) at the end of ICU hospitalization showed diffuse abnormal hyperintense areas involving predominately white matter in both hemispheres and the left cerebellum. A brain MRI nearly 4 years after ICU discharge demonstrated interval development of profound and generalized atrophy with sulcal widening and ventricular enlargement. The magnitude of cognitive decline experienced by ICU survivors is difficult to quantify due to the unavailability of pre-morbid neuropsychological data. The current case, conducted on a patient with baseline neuropsychological data, illustrates the trajectory of decline occurring after critical illness and ICU-associated brain injury with marked atrophy and concomitant cognitive impairments. PMID:19864995
Vandermorris, Susan; Hultsch, David F; Hunter, Michael A; MacDonald, Stuart W S; Strauss, Esther
2011-02-01
Although older adults with Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia as a group, heterogeneity of outcomes is common at the individual level. Using data from a prospective 5-year longitudinal investigation of cognitive change in healthy older adults (N = 262, aged 64-92 years), this study addressed limitations in contemporary MCI identification procedures which rely on single occasion assessment ("Single-Assessment [SA] MCI") by evaluating an alternate operational definition of MCI requiring evidence of persistent cognitive impairment over multiple-testing sessions ("Multiple-Assessment [MA] MCI"). As hypothesized, prevalence of SA-MCI exceeded that of MA-MCI. Further, the MA-MCI groups showed lower baseline cognitive and functional performance and steeper cognitive decline compared with Control and SA-MCI group. Results are discussed with reference to retest effects and clinical implications.
Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.
Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M
2006-01-01
Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.
Effects of head circumference and metabolic syndrome on cognitive decline.
Lee, Kang Soo; Eom, Jin-Sup; Cheong, Hae-Kwan; Oh, Byoung Hoon; Hong, Chang Hyung
2010-01-01
Brain volume progressively decreases with an increase in atrophy, and the brain becomes more susceptible to degenerative brain diseases such as Alzheimer's disease. Metabolic syndrome has also been associated with an increased risk of cognitive decline in the elderly. In this study, we aimed to examine the effects of head circumference and metabolic syndrome on cognitive decline. This study was part of a longitudinal study conducted on Koreans aged 60 years or older. We analyzed a final sample of 596 Korean participants with complete baseline and 2-year follow-up data. The cognitive function of the subjects was assessed using the Korean version of the Mini Mental State Examination (MMSE). Head circumference was measured from the glabella to the occipital protuberance using a measuring tape. Metabolic syndrome was defined according to the NCEP-ATP III standards. Central obesity was assessed on the basis of waist-circumference values, in accordance with the World Health Organization Western Pacific Region report on Asians. We used a longitudinal factorial design in which the MMSE score was the dependent variable, and head circumference and metabolic syndrome were considered as factors. After adjusting the results for age, gender, education, height, weight, baseline MMSE, and number of follow-up years, we observed that smaller head circumference and the presence of metabolic syndrome were independently associated with rapid cognitive decline. All these findings suggest that smaller head circumference and the presence of metabolic syndrome have additive effects on cognitive decline. Copyright 2009 S. Karger AG, Basel.
CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.
Liu, Changqin; Cholerton, Brenna; Shi, Min; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Zhang, Jing
2015-03-01
A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.
Cardiovascular risk factors and dementia.
Fillit, Howard; Nash, David T; Rundek, Tatjana; Zuckerman, Andrea
2008-06-01
Dementias, such as Alzheimer's disease (AD) and vascular dementia, are disorders of aging populations and represent a significant economic burden. Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia. The goal of this review was to discuss the relationship between specific CVD risk factors and dementia and how current treatment strategies for dementia should focus on reducing CVD risks. We conducted a review of the literature for the simultaneous presence of 2 major topics, cardiovascular risk factors and dementia (eg, AD). Special emphasis was placed on clinical outcome studies examining the effects of treatments of pharmacologically modifiable CVD risk factors on dementia and cognitive impairment. Lifestyle risk factors for CVD, such as obesity, lack of exercise, smoking, and certain psychosocial factors, have been associated with an increased risk of cognitive decline and dementia. Some evidence suggests that effectively managing these factors may prevent cognitive decline/dementia. Randomized, placebo-controlled trials of antihypertensive medications have found that such therapy may reduce the risk of cognitive decline, and limited data suggest a benefit for patients with AD. Some small open-label and randomized clinical trials of statins have observed positive effects on cognitive function; larger studies of statins in patients with AD are ongoing. Although more research is needed, current evidence indicates an association between CVD risk factors--such as hypertension, dyslipidemia, and diabetes mellitus--and cognitive decline/dementia. From a clinical perspective, these data further support the rationale for physicians to provide effective management of CVD risk factors and for patients to be compliant with such recommendations to possibly prevent cognitive decline/dementia.
Ma, Duan Yang; Wong, Candy H Y; Leung, Grace T Y; Fung, Ada W T; Chan, Wai Chi; Lam, Linda C W
2017-04-01
This study investigated the potential of physical exercise habit as a lifestyle modification against cognitive and functional decline at the community level. A total of 454 community-dwelling Chinese older adults without dementia participated in the Hong Kong Memory and Ageing Prospective Study at baseline and follow-up at 5 years. Their cognitive and functional performances were assessed by the Cantonese version of the Mini-Mental State Examination (CMMSE) and the Chinese version of Disability Assessment in Dementia (DAD). Hierarchical multiple regression analyses were performed to examine whether physical exercise was a significant predictor of the follow-up CMMSE and DAD scores after controlling for the covariates. Subgroup analyses were performed with a group of 127 participants with mild cognitive impairment at baseline. Physical exercise habit was a significant predictor for both the follow-up CMMSE scores and DAD scores. Participants with exercise habits of 5 years or more showed better cognitive and functional performances at follow-up. Participants who picked up exercise habits only after the baseline assessment also demonstrated better functioning at follow-up. The same patterns were observed in the subgroup analyses with the mild cognitive impairment group. Results suggested that prolonged exercise habit is required for positive effects on cognition to emerge, but benefits on functioning can be observed when individuals take up an exercise habit later in life or even after the beginning of cognitive decline. These findings are encouraging in promoting an exercise habit among older adults living in the community. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain.
Mather, Mara; Harley, Carolyn W
2016-03-01
Research on cognitive aging has focused on how decline in various cortical and hippocampal regions influence cognition. However, brainstem regions play essential modulatory roles, and new evidence suggests that, among these, the integrity of the locus coeruleus (LC)-norepinephrine (NE) system plays a key role in determining late-life cognitive abilities. The LC is especially vulnerable to toxins and infection and is often the first place Alzheimer's-related pathology appears, with most people showing at least some tau pathology by their mid-20s. On the other hand, NE released from the LC during arousing, mentally challenging, or novel situations helps to protect neurons from damage, which may help to explain how education and engaging careers prevent cognitive decline in later years. Copyright © 2016 Elsevier Ltd. All rights reserved.
Laughlin, Gail A; Kritz-Silverstein, Donna; Bergstrom, Jaclyn; Reas, Emilie T; Jassal, Simerjot K; Barrett-Connor, Elizabeth; McEvoy, Linda K
2017-01-01
Evidence of a role for vitamin D (VitD) in cognitive aging is mixed and based primarily on extreme VitD deficiency. We evaluated the association of VitD insufficiency with cognitive function in older, community-dwelling adults living in a temperate climate with year-round sunshine. A population-based longitudinal study of 1,058 adults (median age 75; 62% women) who had cognitive function assessed and serum levels of 25-hydroxyvitaminD (25OHD) measured in 1997-99 and were followed for up to three additional cognitive function assessments over a 12-year period. Overall, 14% (n = 145) of participants had VitD insufficiency defined as 25OHD <30 ng/ml. Adjusting for age, sex, education, and season, VitD insufficiency was associated with poorer baseline performance on the Mini-Mental Status Exam (MMSE) (p = 0.013), Trails Making Test B (Trails B) (p = 0.015), Category Fluency (p = 0.006), and Long Term Retrieval (p = 0.019); differences were equivalent to 5 years of age. For those with VitD insufficiency, the odds of mildly impaired performance at baseline were 38% higher for MMSE (p = 0.08), 78% higher for Trails B (p = 0.017), and 2-fold higher for Category Fluency and Long Term Retrieval (both p = 0.001). VitD insufficiency was not related to the rate of cognitive decline on any test or the risk of developing impaired performance during follow-up. In this population with little VitD deficiency, even moderately low VitD was associated with poorer performance on multiple domains of cognitive function. Low VitD did not predict 12-year cognitive decline. Clinical trials are essential to establish a causal link between VitD and cognitive well-being.
Eckerström, Marie; Göthlin, Mattias; Rolstad, Sindre; Hessen, Erik; Eckerström, Carl; Nordlund, Arto; Johansson, Boo; Svensson, Johan; Jonsson, Michael; Sacuiu, Simona; Wallin, Anders
2017-01-01
Subjective cognitive decline (SCD) and biomarker-based "at-risk" concepts such as "preclinical" Alzheimer's disease (AD) have been developed to predict AD dementia before objective cognitive impairment is detectable. We longitudinally evaluated cognitive outcome when using these classifications. Memory clinic patients ( n = 235) were classified as SCD ( n = 122): subtle cognitive decline ( n = 36) and mild cognitive impairment ( n = 77) and subsequently subclassified into SCDplus and National Institute on Aging-Alzheimer's Association (NIA-AA) stages 0 to 3. Mean (standard deviation) follow-up time was 48 (35) months. Proportion declining cognitively and prognostic accuracy for cognitive decline was calculated for all classifications. Among SCDplus patients, 43% to 48% declined cognitively. Among NIA-AA stage 1 to 3 patients, 50% to 100% declined cognitively. The highest positive likelihood ratios (+LRs) for subsequent cognitive decline (+LR 6.3), dementia (+LR 3.4), and AD dementia (+LR 6.5) were found for NIA-AA stage 2. In a memory clinic setting, NIA-AA stage 2 seems to be the most successful classification in predicting objective cognitive decline, dementia, and AD dementia.
Pakhomov, Serguei VS; Eberly, Lynn; Knopman, David
2016-01-01
A computational approach for estimating several indices of performance on the animal category verbal fluency task was validated, and examined in a large longitudinal study of aging. The performance indices included the traditional verbal fluency score, size of semantic clusters, density of repeated words, as well as measures of semantic and lexical diversity. Change over time in these measures was modeled using mixed effects regression in several groups of participants, including those that remained cognitively normal throughout the study (CN) and those that were diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) dementia at some point subsequent to the baseline visit. The results of the study show that, with the exception of mean cluster size, the indices showed significantly greater declines in the MCI and AD dementia groups as compared to CN participants. Examination of associations between the indices and cognitive domains of memory, attention and visuospatial functioning showed that the traditional verbal fluency scores were associated with declines in all three domains, whereas semantic and lexical diversity measures were associated with declines only in the visuospatial domain. Baseline repetition density was associated with declines in memory and visuospatial domains. Examination of lexical and semantic diversity measures in subgroups with high vs. low attention scores (but normal functioning in other domains) showed that the performance of individuals with low attention was influenced more by word frequency rather than strength of semantic relatedness between words. These findings suggest that various automatically semantic indices may be used to examine various aspects of cognitive performance affected by dementia. PMID:27245645
Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L
2012-10-01
Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.
Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS
Rocca, Maria A.; Leavitt, Victoria M.; Dackovic, Jelena; Mesaros, Sarlota; Drulovic, Jelena; DeLuca, John; Filippi, Massimo
2014-01-01
Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp2 = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.126) and memory (p = 0.037, ηp2 = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS. PMID:24748670
Klepin, Heidi D.; Tooze, Janet A.; Pardee, Timothy S.; Ellis, Leslie R.; Berenzon, Dmitriy; Mihalko, Shannon L.; Danhauer, Suzanne C.; Rao, Arati V.; Wildes, Tanya M.; Williamson, Jeff D.; Powell, Bayard L.; Kritchevsky, Stephen B.
2016-01-01
OBJECTIVES To measure short-term changes in physical and cognitive function and emotional well-being of older adults receiving intensive chemotherapy for acute myeloid leukemia (AML). DESIGN Prospective observational study. SETTING Single academic institution. PARTICIPANTS Individuals aged 60 and older with newly diagnosed AML who received induction chemotherapy (N = 49, mean age 70 ± 6.2, 56% male). MEASUREMENTS Geriatric assessment (GA) was performed during inpatient examination for AML and within 8 weeks after hospital discharge after induction chemotherapy. Measures were the Pepper Assessment Tool for Disability (activity of daily living, instrumental activity of daily living (IADL), mobility questions), Short Physical Performance Battery (SPPB), grip strength, Modified Mini-Mental State examination, Center for Epidemiologic Studies Depression Scale, and the Distress Thermometer. Changes in GA measures were assessed using paired t-tests. Analysis of variance models were used to evaluate relationships between GA variables and change in function over time. RESULTS After chemotherapy, IADL dependence worsened (mean 1.4 baseline vs 2.1 follow-up, P < .001), as did mean SPPB scores (7.5 vs 5.9, P = .02 for total). Grip strength also declined (38.9 ± 7.7 vs 34.2 ± 10.3 kg, P < .001 for men; 24.5 ± 4.8 vs 21.8 ± 4.7 kg, P = .007 for women). No significant changes in cognitive function (mean 84.7 vs 85.1, P = .72) or depressive symptoms (14.0 vs. 11.3, P = .11) were detected, but symptoms of distress declined (5.0 vs 3.2, P < .001). Participants with depressive symptoms at baseline and follow-up had greater declines in SPPB scores those without at both time points. CONCLUSIONS Short-term survivors of intensive chemotherapy for AML had clinically meaningful declines in physical function. These data support the importance of interventions to maintain physical function during and after chemotherapy. Depressive symptoms before and during chemotherapy may be linked to potentially modifiable physical function declines. PMID:27627675
Wong, F Lennie; Francisco, Liton; Togawa, Kayo; Kim, Heeyoung; Bosworth, Alysia; Atencio, Liezl; Hanby, Cara; Grant, Marcia; Kandeel, Fouad; Forman, Stephen J; Bhatia, Smita
2013-12-05
This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51% (P = .01) in men and increased to 48% (P = .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P ≤ .001). Orgasm (P = .002) and drive/relationship (P < .001) declined in men, but sexual cognition/fantasy (P = .01) and sexual behavior/experience (P = .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P = .003) and orgasm (P = .006) in men and sexual arousal (P = .05) and sexual satisfaction (P = .005) in women. All male sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being.
Wong, F. Lennie; Francisco, Liton; Togawa, Kayo; Kim, Heeyoung; Bosworth, Alysia; Atencio, Liezl; Hanby, Cara; Grant, Marcia; Kandeel, Fouad; Forman, Stephen J.
2013-01-01
This prospective study described the trajectory of sexual well-being from before hematopoietic cell transplantation (HCT) to 3 years after in 131 allogeneic and 146 autologous HCT recipients using Derogatis Interview for Sexual Function and Derogatis Global Sexual Satisfaction Index. Sixty-one percent of men and 37% of women were sexually active pre-HCT; the prevalence declined to 51% (P = .01) in men and increased to 48% (P = .02) in women at 3 years post-HCT. After HCT, sexual satisfaction declined in both sexes (P < .001). All sexual function domains were worse in women compared with men (P ≤ .001). Orgasm (P = .002) and drive/relationship (P < .001) declined in men, but sexual cognition/fantasy (P = .01) and sexual behavior/experience (P = .01) improved in women. Older age negatively impacted sexual function post-HCT in both sexes (P < .01). Chronic graft-versus-host disease was associated with lower sexual cognition/fantasy (P = .003) and orgasm (P = .006) in men and sexual arousal (P = .05) and sexual satisfaction (P = .005) in women. All male sexual function domains declined after total body irradiation (P < .05). This study identifies vulnerable subpopulations that could benefit from interventional strategies to improve sexual well-being. PMID:24159171
Intradialytic Cognitive and Exercise Training May Preserve Cognitive Function.
McAdams-DeMarco, Mara A; Konel, Jonathan; Warsame, Fatima; Ying, Hao; Fernández, Marlís González; Carlson, Michelle C; Fine, Derek M; Appel, Lawrence J; Segev, Dorry L
2018-01-01
Cognitive decline is common and increases mortality risk in hemodialysis patients. Intradialytic interventions like cognitive training (CT) and exercise training (ET) may preserve cognitive function. We conducted a pilot randomized controlled trial of 20 hemodialysis patients to study the impact of 3 months of intradialytic CT (tablet-based brain games) (n = 7), ET (foot peddlers) (n = 6), or standard of care (SC) (n = 7) on cognitive function. Global cognitive function was measured by the Modified Mini Mental Status Exam (3MS), psychomotor speed was measured by Trail Making Tests A and B (TMTA and TMTB), and executive function was assessed by subtracting (TMTB - TMTA). Lower 3MS scores and slower TMTA and TMTB times reflected worse cognitive function. P values for differences were generated using analysis of variance, and 95% confidence intervals (CIs) and P values were generated from linear regression. Patients with SC experienced a decrease in psychomotor speed and executive function by 3 months (TMTA: 15 seconds; P = 0.055; TMTB: 47.4 seconds; P = 0.006; TMTB - TMTA; 31.7 seconds; P = 0.052); this decline was not seen among those with CT or ET (all P > 0.05). Compared with SC, the difference in the mean change in 3MS score was -3.29 points (95% CI: -11.70 to 5.12; P = 0.42) for CT and 4.48 points (95% CI: -4.27 to 13.22; P = 0.30) for ET. Compared with SC, the difference in mean change for TMTA was -15.13 seconds (95% CI: -37.64 to 7.39; P = 0.17) for CT and -17.48 seconds (95% CI: -41.18 to 6.22; P = 0.14) for ET, for TMTB, the difference was -46.72 seconds (95% CI: -91.12 to -2.31; P = 0.04) for CT and -56.21 seconds (95% CI: -105.86 to -6.56; P = 0.03) for ET, and for TMTB - TMTA, the difference was -30.88 seconds (95% CI: -76.05 to 14.28; P = 0.16) for CT and -34.93 seconds (95% CI: -85.43 to 15.56; P = 0.16) for ET. Preliminary findings of our pilot study suggested that cognitive decline in psychomotor speed and executive function is possibly prevented by intradialytic CT and ET. These preliminary pilot findings should be replicated.
Xavier, Shannon; Best, Michael W; Schorr, Emily; Bowie, Christopher R
2015-01-01
Schizotypy is phenologically and genetically related to schizophrenia-spectrum illness. Previous studies find cognitive function to be mildly impaired, but specific impairments and their relationship to functioning are not well understood. In this study, we sought to examine how cognitive load affects performance in schizotypy and to examine whether impairments might manifest in functional capacity and quality of life. Undergraduate students were screened for abnormally high levels of schizotypy (N = 72) and compared to those without psychopathology (N = 80) on a standard battery of neuropsychological tests, cognitive tests with varying cognitive load, functional capacity measures and quality of life. The high schizotypy group did not differ from controls on traditional measures of neuropsychological functioning, but an interaction of group by cognitive load was observed, where those with schizotypy manifested a greater decline in performance as information processing load was parametrically increased. Differences in functioning were observed and cognitive impairment was associated with impaired functioning. Cognitive and functional impairment can be observed in those with high schizotypal traits who are non-treatment seeking. The sensitivity of cognitive tests to impairment in this population might be a function of their ability to parametrically increase cognitive load.
Cognitive decline and quality of life in incident Parkinson's disease: The role of attention.
Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Breen, David P; Khoo, Tien K; Williams-Gray, Caroline H; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J
2016-06-01
Parkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort. Recently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition. Baseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = -2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = -0.4, p < 0.01). PD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Cognitive functioning and its influence on sexual behavior in normal aging and dementia.
Hartmans, Carien; Comijs, Hannie; Jonker, Cees
2014-05-01
Motivational aspects, emotional factors, and cognition, all of which require intact cognitive functioning may be essential in sexual functioning. However, little is known about the association between cognitive functioning and sexual behavior. The aim of this article is to review the current evidence for the influence of cognitive functioning on sexual behavior in normal aging and dementia. A systematic literature search was conducted in PubMed, Ovid, Cochrane, and PsycINFO databases. The databases were searched for English language papers focusing on human studies published relating cognitive functioning to sexual behavior in the aging population. Keywords included sexual behavior, sexuality, cognitive functioning, healthy elderly, elderly, aging and dementia. Eight studies fulfilled our inclusion criteria. Of these studies, five included dementia patients and/or their partners, whereas only three studies included healthy older persons. Although not consistently, results indicated a trend that older people who are not demented and continue to engage in sexual activity have better overall cognitive functioning. Cognitive decline and dementia seem to be associated with diminished sexual behavior in older persons. The association between cognitive functioning and sexual behavior in the aging population is understudied. The results found are inconclusive. Copyright © 2013 John Wiley & Sons, Ltd.
Bernard, Jessica A.; Seidler, Rachael D.
2013-01-01
The cerebellum has been implicated in both sensorimotor and cognitive function, but is known to undergo volumetric declines with advanced age. Individual differences in regional cerebellar volume may therefore provide insight into performance variability across the lifespan, as has been shown with other brain structures and behaviors. Here, we investigated whether there are regional age differences in cerebellar volume in young and older adults, and whether these volumes explain, in part, individual differences in sensorimotor and cognitive task performance. We found that older adults had smaller cerebellar volume than young adults; specifically, lobules in the anterior cerebellum were more impacted by age. Multiple regression analyses for both age groups revealed associations between sensorimotor task performance in several domains (balance, choice reaction time, and timing) and regional cerebellar volume. There were also relationships with working memory, but none with measures of general cognitive or executive function. Follow-up analyses revealed several differential relationships with age between regional volume and sensorimotor performance. These relationships were predominantly selective to cerebellar regions that have been implicated in cognitive functions. Therefore, it may be the cognitive aspects of sensorimotor task performance that are best explained by individual differences in regional cerebellar volumes. In sum, our results demonstrate the importance of regional cerebellar volume with respect to both sensorimotor and cognitive performance, and we provide additional insight into the role of the cerebellum in age-related performance declines. PMID:23625382
Disrupted white matter structure underlies cognitive deficit in hypertensive patients.
Li, Xin; Ma, Chao; Sun, Xuan; Zhang, Junying; Chen, Yaojing; Chen, Kewei; Zhang, Zhanjun
2016-09-01
Hypertension is considered a risk factor of cognitive impairments and could result in white matter changes. Current studies on hypertension-related white matter (WM) changes focus only on regional changes, and the information about global changes in WM structure network is limited. We assessed the cognitive function in 39 hypertensive patients and 37 healthy controls with a battery of neuropsychological tests. The WM structural networks were constructed by utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. The direct and indirect correlations among cognitive impairments, brain WM network disruptions and hypertension were analyzed with structural equation modelling (SEM). Hypertensive patients showed deficits in executive function, memory and attention compared with controls. An aberrant connectivity of WM networks was found in the hypertensive patients (P Eglob = 0.005, P Lp = 0.005), especially in the frontal and parietal regions. Importantly, SEM analysis showed that the decline of executive function resulted from aberrant WM networks in hypertensive patients (p = 0.3788, CFI = 0.99). These results suggest that the cognitive decline in hypertensive patients was due to frontal and parietal WM disconnections. Our findings highlight the importance of brain protection in hypertension patients. • Hypertension has a negative effect on the performance of the cognitive domains • Reduced efficiencies of white matter networks were shown in hypertension • Disrupted white matter networks are responsible for poor cognitive function in hypertension.
Ray, Nicola J; Bradburn, Steven; Murgatroyd, Christopher; Toseeb, Umar; Mir, Pablo; Kountouriotis, George K; Teipel, Stefan J; Grothe, Michel J
2018-01-01
See Gratwicke and Foltynie (doi:10.1093/brain/awx333) for a scientific commentary on this article.Cognitive impairments are a prevalent and disabling non-motor complication of Parkinson's disease, but with variable expression and progression. The onset of serious cognitive decline occurs alongside substantial cholinergic denervation, but imprecision of previously available techniques for in vivo measurement of cholinergic degeneration limit their use as predictive cognitive biomarkers. However, recent developments in stereotactic mapping of the cholinergic basal forebrain have been found useful for predicting cognitive decline in prodromal stages of Alzheimer's disease. These methods have not yet been applied to longitudinal Parkinson's disease data. In a large sample of people with de novo Parkinson's disease (n = 168), retrieved from the Parkinson's Progressive Markers Initiative database, we measured cholinergic basal forebrain volumes, using morphometric analysis of T1-weighted images in combination with a detailed stereotactic atlas of the cholinergic basal forebrain nuclei. Using a binary classification procedure, we defined patients with reduced basal forebrain volumes (relative to age) at baseline, based on volumes measured in a normative sample (n = 76). Additionally, relationships between the basal forebrain volumes at baseline, risk of later cognitive decline, and scores on up to 5 years of annual cognitive assessments were assessed with regression, survival analysis and linear mixed modelling. In patients, smaller volumes in a region corresponding to the nucleus basalis of Meynert were associated with greater change in global cognitive, but not motor scores after 2 years. Using the binary classification procedure, patients classified as having smaller than expected volumes of the nucleus basalis of Meynert had ∼3.5-fold greater risk of being categorized as mildly cognitively impaired over a period of up to 5 years of follow-up (hazard ratio = 3.51). Finally, linear mixed modelling analysis of domain-specific cognitive scores revealed that patients classified as having smaller than expected nucleus basalis volumes showed more severe and rapid decline over up to 5 years on tests of memory and semantic fluency, but not on tests of executive function. Thus, we provide the first evidence that volumetric measurement of the nucleus basalis of Meynert can predict early cognitive decline. Our methods therefore provide the opportunity for multiple-modality biomarker models to include a cholinergic biomarker, which is currently lacking for the prediction of cognitive deterioration in Parkinson's disease. Additionally, finding dissociated relationships between nucleus basalis status and domain-specific cognitive decline has implications for understanding the neural basis of heterogeneity of Parkinson's disease-related cognitive decline. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.
ERIC Educational Resources Information Center
Tucker-Drob, Elliot M.; Johnson, Kathy E.; Jones, Richard N.
2009-01-01
The term cognitive reserve is frequently used to refer to the ubiquitous finding that, during later life, those higher in experiential resources (e.g., education, knowledge) exhibit higher levels of cognitive function. This observation may be the result of either experiential resources playing protective roles with respect to the cognitive…
ERIC Educational Resources Information Center
Chapman, Sandra Bond; Weiner, Myron F.; Rackley, Audette; Hynan, Linda S.; Zientz, Jennifer
2004-01-01
ds to growing evidence that active cognitive stimulation may slow the rate of verbal and functional decline and decrease negative emotional symptoms in AD when combined with acetylcholinesterase inhibitors, indicating a need to advance research in the area of cognitive treatments. The fact that AD is a progressive brain disease should not preclude…
Passow, Susanne; Thurm, Franka; Li, Shu-Chen
2017-01-01
Existing neurocomputational and empirical data link deficient neuromodulation of the fronto-parietal and hippocampal-striatal circuitries with aging-related increase in processing noise and declines in various cognitive functions. Specifically, the theory of aging neuronal gain control postulates that aging-related suboptimal neuromodulation may attenuate neuronal gain control, which yields computational consequences on reducing the signal-to-noise-ratio of synaptic signal transmission and hampering information processing within and between cortical networks. Intervention methods such as cognitive training and non-invasive brain stimulation, e.g., transcranial direct current stimulation (tDCS), have been considered as means to buffer cognitive functions or delay cognitive decline in old age. However, to date the reported effect sizes of immediate training gains and maintenance effects of a variety of cognitive trainings are small to moderate at best; moreover, training-related transfer effects to non-trained but closely related (i.e., near-transfer) or other (i.e., far-transfer) cognitive functions are inconsistent or lacking. Similarly, although applying different tDCS protocols to reduce aging-related cognitive impairments by inducing temporary changes in cortical excitability seem somewhat promising, evidence of effects on short- and long-term plasticity is still equivocal. In this article, we will review and critically discuss existing findings of cognitive training- and stimulation-related behavioral and neural plasticity effects in the context of cognitive aging, focusing specifically on working memory and episodic memory functions, which are subserved by the fronto-parietal and hippocampal-striatal networks, respectively. Furthermore, in line with the theory of aging neuronal gain control we will highlight that developing age-specific brain stimulation protocols and the concurrent applications of tDCS during cognitive training may potentially facilitate short- and long-term cognitive and brain plasticity in old age. PMID:28280465
Statistical Model of Dynamic Markers of the Alzheimer's Pathological Cascade.
Balsis, Steve; Geraci, Lisa; Benge, Jared; Lowe, Deborah A; Choudhury, Tabina K; Tirso, Robert; Doody, Rachelle S
2018-05-05
Alzheimer's disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statistically challenging because of the multivariate nature of the data. To address this challenge, we implemented advanced statistical analyses designed specifically to model complex data across a single continuum. We analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 1,056), focusing on indicators from the assessments of magnetic resonance imaging (MRI) volume, fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic activity, cognitive performance, and adaptive function. Item response theory was used to identify the continuum of decline. Then, through a process of statistical scaling, indicators across all modalities were linked to that continuum and analyzed. Findings revealed that measures of MRI volume, FDG-PET metabolic activity, and adaptive function added measurement precision beyond that provided by cognitive measures, particularly in the relatively mild range of disease severity. More specifically, MRI volume, and FDG-PET metabolic activity become compromised in the very mild range of severity, followed by cognitive performance and finally adaptive function. Our statistically derived models of the AD pathological cascade are consistent with existing theoretical models.
Florbetapir F 18 amyloid PET and 36-month cognitive decline: a prospective multicenter study.
Doraiswamy, P M; Sperling, R A; Johnson, K; Reiman, E M; Wong, T Z; Sabbagh, M N; Sadowsky, C H; Fleisher, A S; Carpenter, A; Joshi, A D; Lu, M; Grundman, M; Mintun, M A; Skovronsky, D M; Pontecorvo, M J
2014-09-01
This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ-), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ- subjects on the ADAS-Cog over 36 months (5.66 ± 1.47 vs -0.71 ± 1.09, P = 0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution (DSS) test, and a verbal fluency test (P < 0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P < 0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ- subjects do.
Parikh, Mili; Hynan, Linda S; Weiner, Myron F; Lacritz, Laura; Ringe, Wendy; Cullum, C Munro
2014-01-01
Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.