Aging and the shape of cognitive change before death: terminal decline or terminal drop?

PubMed

MacDonald, Stuart W S; Hultsch, David F; Dixon, Roger A

2011-05-01

Relative to typical age-related cognitive decrements, the terms "terminal decline" and "terminal drop" refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n=265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual.

Evidence for age-associated cognitive decline from Internet game scores.

PubMed

Geyer, Jason; Insel, Philip; Farzin, Faraz; Sternberg, Daniel; Hardy, Joseph L; Scanlon, Michael; Mungas, Dan; Kramer, Joel; Mackin, R Scott; Weiner, Michael W

2015-06-01

Lumosity's Memory Match (LMM) is an online game requiring visual working memory. Change in LMM scores may be associated with individual differences in age-related changes in working memory. Effects of age and time on LMM learning and forgetting rates were estimated using data from 1890 game sessions for users aged 40 to 79 years. There were significant effects of age on baseline LMM scores (β = -.31, standard error or SE = .02, P < .0001) and lower learning rates (β = -.0066, SE = .0008, P < .0001). A sample size of 202 subjects/arm was estimated for a 1-year study for subjects in the lower quartile of game performance. Online memory games have the potential to identify age-related decline in cognition and to identify subjects at risk for cognitive decline with smaller sample sizes and lower cost than traditional recruitment methods.

Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

PubMed

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.

Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

PubMed Central

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

Aging and the Shape of Cognitive Change Before Death: Terminal Decline Or Terminal Drop?

PubMed Central

Hultsch, David F.; Dixon, Roger A.

2011-01-01

Objectives. Relative to typical age-related cognitive decrements, the terms “terminal decline” and “terminal drop” refer to the phenomenon of increased cognitive decline in proximity to death. Given that these terms are not necessarily synonymous, we examined the important theoretical distinction between the two alternative trajectories or shapes of changes they imply. Methods. We used 12-year (5-wave) data from the Victoria Longitudinal Study to directly test whether pre-death cognitive decrements follow a terminal decline (generally gradual) or a terminal drop (more abrupt) shape. Pre-death trajectories of cognitive decline for n = 265 decedents (Mage = 72.67 years, SD = 6.44) were examined separately for 5 key cognitive constructs (verbal speed, working memory, episodic memory, semantic memory, and crystallized ability). Results. Several classes of linear mixed models evaluated whether cognitive decline increased per additional year closer to death. Findings indicated that the shape of pre-death cognitive change was predominantly characterized by decline that is steeper as compared with typical aging-related change, but still best described as slow and steady decline, especially as compared with precipitous drop. Discussion. The present findings suggest that terminal decline and terminal drop trajectories may not be mutually exclusive but could rather reflect distinct developmental trajectories within the same individual. PMID:21300703

Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition.

PubMed

Meyers, Emily A; Gobeske, Kevin T; Bond, Allison M; Jarrett, Jennifer C; Peng, Chian-Yu; Kessler, John A

2016-02-01

Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. Copyright © 2016 Elsevier Inc. All rights reserved.

Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

ERIC Educational Resources Information Center

Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

2008-01-01

Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

Age-dependent effects of carotid endarterectomy or stenting on cognitive performance.

PubMed

Wasser, Katrin; Hildebrandt, Helmut; Gröschel, Sonja; Stojanovic, Tomislav; Schmidt, Holger; Gröschel, Klaus; Pilgram-Pastor, Sara M; Knauth, Michael; Kastrup, Andreas

2012-11-01

Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (<68 years and ≥68 years); 27 healthy subjects served as a control group. In all patients clinical examinations, MRI scans and a neuropsychological test battery that assessed four major cognitive domains were performed immediately before, within 72 h, and 3 months after CEA or CAS. While patients <68 years of age showed no significant cognitive alteration after either CEA or CAS, a significant cognitive decline was observed in patients ≥68 years in both treatment groups (p = 0.001). Notably, this cognitive deterioration persisted in patients after CEA, whereas it was only transient in patients treated with CAS. These results demonstrate an age-dependent effect of CEA and CAS on cognitive functions. In contrast to the recently observed increased clinical complication rates in older subjects after CAS compared with CEA, CEA appears to be associated with a greater, persistent decline in cognitive performance than CAS in this subgroup of patients.

Vitamin K Status Is not Associated with Cognitive Decline in Middle Aged Adults.

PubMed

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.

A prospectus for ethical analysis of ageing individuals' responsibility to prevent cognitive decline.

PubMed

Forlini, Cynthia; Hall, Wayne

2017-11-01

As the world's population ages, governments and non-governmental organizations in developed countries are promoting healthy cognitive ageing to reduce the rate of age-related cognitive decline and sustain economic productivity in an ageing workforce. Recommendations from the Productivity Commission (Australia), Dementia Australia, Government Office for Science (UK), Presidential Commission for the Study of Bioethical Issues (USA), Institute of Medicine (USA), among others, are encouraging older adults to engage in mental, physical, and social activities. These lifestyle recommendations for healthy cognitive ageing are timely and well supported by scientific evidence but they make implicit normative judgments about the responsibility of ageing individuals to prevent cognitive decline. Ethical tensions arise when this individual responsibility collides with social and personal realities of ageing populations. First, we contextualize the priority given to healthy cognitive ageing within the current brain-based medical and social discourses. Second, we explore the individual responsibility by examining the economic considerations, medical evidence and individual interests that relate to the priority given to healthy cognitive ageing. Third, we identify three key ethical challenges for policymakers seeking to implement lifestyle recommendations as an effective population-level approach to healthy cognitive ageing. The result is a prospectus for future in-depth analysis of ethical tensions that arise from current policy discussions of healthy cognitive ageing. © 2017 John Wiley & Sons Ltd.

Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline

PubMed Central

Roberts, Katherine L.; Allen, Harriet A.

2016-01-01

Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age. PMID:26973514

Greater cognitive decline with aging among elders with high serum concentrations of organochlorine pesticides.

PubMed

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

Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

PubMed

Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

2018-03-01

Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment.

PubMed

Pace-Schott, Edward F; Spencer, Rebecca M C

2015-01-01

Sleep quality and architecture as well as sleep's homeostatic and circadian controls change with healthy aging. Changes include reductions in slow-wave sleep's (SWS) percent and spectral power in the sleep electroencephalogram (EEG), number and amplitude of sleep spindles, rapid eye movement (REM) density and the amplitude of circadian rhythms, as well as a phase advance (moved earlier in time) of the brain's circadian clock. With mild cognitive impairment (MCI) there are further reductions of sleep quality, SWS, spindles, and percent REM, all of which further diminish, along with a profound disruption of circadian rhythmicity, with the conversion to Alzheimer's disease (AD). Sleep disorders may represent risk factors for dementias (e.g., REM Behavior Disorder presages Parkinson's disease) and sleep disorders are themselves extremely prevalent in neurodegenerative diseases. Working memory , formation of new episodic memories, and processing speed all decline with healthy aging whereas semantic, recognition, and emotional declarative memory are spared. In MCI, episodic and working memory further decline along with declines in semantic memory. In young adults, sleep-dependent memory consolidation (SDC) is widely observed for both declarative and procedural memory tasks. However, with healthy aging, although SDC for declarative memory is preserved, certain procedural tasks, such as motor-sequence learning, do not show SDC. In younger adults, fragmentation of sleep can reduce SDC, and a normative increase in sleep fragmentation may account for reduced SDC with healthy aging. Whereas sleep disorders such as insomnia, obstructive sleep apnea, and narcolepsy can impair SDC in the absence of neurodegenerative changes, the incidence of sleep disorders increases both with normal aging and, further, with neurodegenerative disease. Specific features of sleep architecture, such as sleep spindles and SWS are strongly linked to SDC. Diminution of these features with healthy aging

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency.

PubMed

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.

Prevalence of ageing-associated cognitive decline in an elderly population.

PubMed

Hanninen, T; Koivisto, K; Reinikainen, K J; Helkala, E L; Soininen, H; Mykkänen, L; Laakso, M; Riekkinen, P J

1996-05-01

Different diagnostic definitions have been proposed for use in the characterization of mild cognitive disorders associated with ageing. Previously, we reported a high (38.4%) prevalence of age-associated memory impairment (AAMI) using the National Institute of Mental Health criteria in an elderly population. Recently, a work group of the International Psychogeriatric Association proposed criteria for 'ageing-associated cognitive decline' (AACD). The objective of this study was to evaluate the prevalence of AACD in an elderly population. We examined 403 randomly selected subjects (68-78 years of age) with tests of memory, cognitive processing, attention, verbal and visuoconstructive functions and with a structured questionnaire for health status and subjective complaints of cognitive decline. In all, 26.6% of the subjects (24.4% of women, 30. 1% or men) fulfilled the AACD criteria. The prevalence was slightly related to age and education. The rate was lowest in the oldest age of 75 - 78 years (20.5%) and highest in the age of 71 -74 years (30%). Subjects with less than 4 years of education had the lowest (14.3%) and subjects with more than 6 years of education had the highest rate (29.4%) for AACD. However, the differences between these subgroups were not statistically significant. These results suggest that the prevalence of AACD is lower than that of AAMI. As AAMI tends to identify a very heterogeneous subject group, the AACD diagnosis, which takes into account age and education specific norms in its inclusion criteria, might prove superior to AAMI in differentiating a meaningful subgroup from an elderly population both for research purposes and in clinical settings.

Moving Forward: Age Effects on the Cerebellum Underlie Cognitive and Motor Declines

PubMed Central

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

Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study.

PubMed

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.

Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition.

PubMed

Salami, Alireza; Eriksson, Johan; Nilsson, Lars-Göran; Nyberg, Lars

2012-03-01

Aging is associated with declining cognitive performance as well as structural changes in brain gray and white matter (WM). The WM deterioration contributes to a disconnection among distributed brain networks and may thus mediate age-related cognitive decline. The present diffusion tensor imaging (DTI) study investigated age-related differences in WM microstructure and their relation to cognition (episodic memory, visuospatial processing, fluency, and speed) in a large group of healthy subjects (n=287) covering 6 decades of the human life span. Age related decreases in fractional anisotropy (FA) and increases in mean diffusivity (MD) were observed across the entire WM skeleton as well as in specific WM tracts, supporting the WM degeneration hypothesis. The anterior section of the corpus callosum was more susceptible to aging compared to the posterior section, lending support to the anterior-posterior gradient of WM integrity in the corpus callosum. Finally, and of critical interest, WM integrity differences were found to mediate age-related reductions in processing speed but no significant mediation was found for episodic memory, visuospatial ability, or fluency. These findings suggest that compromised WM integrity is not a major contributing factor to declining cognitive performance in normal aging. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency

PubMed Central

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

The therapeutic potential of metabolic hormones in the treatment of age-related cognitive decline and Alzheimer’s disease

PubMed Central

Grizzanti, John; Lee, Hyoung-Gon; Camins, Antoni; Pallas, Merce; Casadesus, Gemma

2017-01-01

Aging leads to a number of physiological alterations, specifically changes in circulating hormone levels, increases in fat deposition, decreases in metabolism, changes in inflammatory responses, and reductions in growth factors. These progressive changes in physiology and metabolism are exacerbated by modern culture and Western diet and give rise to diseases such as obesity, metabolic syndrome, and type 2 (non–insulin-dependent) diabetes (T2D). These age and lifestyle-related metabolic diseases are often accompanied by insulin and leptin resistance, as well as aberrant amylin production and signaling. Many of these alterations in hormone production and signaling are directly influenced by an increase in both oxidative stress and inflammation. Importantly, changes in hormone production and signaling have direct effects on brain function and the development of age-related neurologic disorders. Therefore, this review aims to present evidence on the effects that diet and metabolic disease have on age-related cognitive decline and the development of cognitive diseases, particularly Alzheimer disease. This review will focus on the metabolic hormones insulin, leptin, and amylin and their role in cognitive decline, as well as the therapeutic potential of these hormones in treating cognitive disease. Future investigations targeting the long-term effects of insulin and leptin treatment may reveal evidence to reduce risk of cognitive decline and Alzheimer disease. PMID:27923524

Learning to remember: cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains.

PubMed

Talboom, Joshua S; West, Stephen G; Engler-Chiurazzi, Elizabeth B; Enders, Craig K; Crain, Ian; Bimonte-Nelson, Heather A

2014-12-01

Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6 to 18 months old on the same T-maze; Group one received a version testing spatial reference memory, and Group two received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats, respectively. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. Group five of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects, since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which were related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. Published by Elsevier Inc.

Learning to remember: Cognitive training-induced attenuation of age-related memory decline depends on sex and cognitive demand, and can transfer to untrained cognitive domains

PubMed Central

Talboom, Joshua S.; West, Stephen G.; Engler-Chiurazzi, Elizabeth B.; Enders, Craig K.; Crain, Ian; Bimonte-Nelson, Heather A.

2014-01-01

Aging is associated with progressive changes in learning and memory. A potential approach to attenuate age-related cognitive decline is cognitive training. In this study, adult male and female rats were given either repeated exposure to a T-maze, or no exposure to any maze, and then tested on a final battery of cognitive tasks. Two groups of each sex were tested from 6-18 months old on the same T-maze; one group received a version testing spatial reference memory, and the other group received only the procedural testing components with minimal cognitive demand. Groups three and four of each sex had no maze exposure until the final battery, and were comprised of aged or young rats. The final maze battery included the practiced T-maze plus two novel tasks, one with a similar, and one with a different, memory type to the practice task. The fifth group of each sex was not maze tested, serving as an aged control for the effects of maze testing on neurotrophin protein levels in cognitive brain regions. Results showed that adult intermittent cognitive training enhanced performance on the practice task when aged in both sexes, that cognitive training benefits transferred to novel tasks only in females, and that cognitive demand was necessary for these effects since rats receiving only the procedural testing components showed no improvement on the final maze battery. Further, for both sexes, rats that showed faster learning when young demonstrated better memory when aged. Age-related increases in neurotrophin concentrations in several brain regions were revealed, which was related to performance on the training task only in females. This longitudinal study supports the tenet that cognitive training can help one remember later in life, with broader enhancements and associations with neurotrophins in females. PMID:25104561

Differential effects of enriched environment at work on cognitive decline in old age.

PubMed

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.

Cognitive decline, mortality, and organophosphorus exposure in aging Mexican Americans.

PubMed

Paul, Kimberly C; Ling, Chenxiao; Lee, Anne; To, Tu My; Cockburn, Myles; Haan, Mary; Ritz, Beate

2018-01-01

Cognitive impairment is a major health concern among older Mexican Americans, associated with significant morbidity and mortality, and may be influenced by environmental exposures. To investigate whether agricultural based ambient organophosphorus (OP) exposure influences 1) the rate of cognitive decline and mortality and 2) whether these associations are mediated through metabolic or inflammatory biomarkers. In a subset of older Mexican Americans from the Sacramento Area Latino Study on Aging (n = 430), who completed modified mini-mental state exams (3MSE) up to 7 times (1998-2007), we examined the relationship between estimated ambient OP exposures and cognitive decline (linear repeated measures model) and time to dementia or being cognitively impaired but not demented (CIND) and time to mortality (cox proportional hazards model). We then explored metabolic and inflammatory biomarkers as potential mediators of these relationships (additive hazards mediation). OP exposures at residential addresses were estimated with a geographic information system (GIS) based exposure assessment tool. Participants with high OP exposure in the five years prior to baseline experienced faster cognitive decline (β = 0.038, p = 0.02) and higher mortality over follow-up (HR = 1.91, 95% CI = 1.12, 3.26). The direct effect of OP exposure was estimated at 241 (95% CI = 27-455) additional deaths per 100,000 person-years, and the proportion mediated through the metabolic hormone adiponectin was estimated to be 4% 1.5-19.2). No other biomarkers were associated with OP exposure. Our study provides support for the involvement of OP pesticides in cognitive decline and mortality among older Mexican Americans, possibly through biologic pathways involving adiponectin. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluating Alzheimer's disease biomarkers as mediators of age-related cognitive decline.

PubMed

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.

Age as a Predictor of Cognitive Decline in Bipolar Disorder

PubMed Central

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

Fish consumption, intake of fats and cognitive decline at middle and older age: the Doetinchem Cohort Study.

PubMed

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.

Central obesity, leptin and cognitive decline: the Sacramento Area Latino Study on Aging.

PubMed

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.

Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline.

PubMed

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.

Visual function and cognitive speed of processing mediate age-related decline in memory span and fluid intelligence

PubMed Central

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

Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

PubMed Central

Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

2015-01-01

Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

Subjective cognitive decline and fall risk in community-dwelling older adults with or without objective cognitive decline.

PubMed

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.

Use it or lose it: engaged lifestyle as a buffer of cognitive decline in aging?

PubMed

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.

Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats.

PubMed

Pietrelli, A; Lopez-Costa, J; Goñi, R; Brusco, A; Basso, N

2012-01-27

Recent research involving human and animals has shown that aerobic exercise of moderate intensity produces the greatest benefit on brain health and behavior. In this study we investigated the effects on cognitive function and anxiety-related behavior in rats at different ages of aerobic exercise, performed regularly throughout life. We designed an aerobic training program with the treadmill running following the basic principles of human training, and assuming that rats have the same physiological adaptations. The intensity was gradually adjusted to the fitness level and age, and maintained at 60-70% of maximum oxygen consumption (max.VO(2)). In middle age (8 months) and old age (18 months), we studied the cognitive response with the radial maze (RM), and anxiety-related behaviors with the open field (OF) and the elevated plus maze (EPM). Aerobically trained (AT) rats had a higher cognitive performance measured in the RM, showing that exercise had a cumulative and amplifier effect on memory and learning. The analysis of age and exercise revealed that the effects of aerobic exercise were modulated by age. Middle-aged AT rats were the most successful animals; however, the old AT rats met the criteria more often than the middle-aged sedentary controls (SC), indicating that exercise could reverse the negative effects of sedentary life, partially restore the cognitive function, and protect against the deleterious effects of aging. The results in the OF and EPM showed a significant decrease in key indicators of anxiety, revealing that age affected most of the analyzed variables, and that exercise had a prominent anxiolytic effect, particularly strong in old age. In conclusion, our results indicated that regular and chronic aerobic exercise has time and dose-dependent, neuroprotective and restorative effects on physiological brain aging, and reduces anxiety-related behaviors. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

High-sensitivity C-reactive protein and cognitive decline: the English Longitudinal Study of Ageing.

PubMed

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.

Protective Effects of Foods Containing Flavonoids on Age-Related Cognitive Decline.

PubMed

Gildawie, Kelsea R; Galli, Rachel L; Shukitt-Hale, Barbara; Carey, Amanda N

2018-06-01

Evidence suggests that flavonoids, polyphenolic compounds found in many plant-derived foods, such as berries, may allay cognitive impairment. We review recent research exploring the protective effects of flavonoids on age-related cognitive decline and neurodegenerative disorders in humans and animals. We also address the mechanisms by which flavonoids may exert their effects and promising avenues of future research. Flavonoids have been found to decrease neuroinflammation, reduce oxidative stress, and mediate neuroplasticity in animal models of neurodegeneration and aging. Injecting flavonoids encased in metal nanoparticles may further enhance the efficacy of flavonoids. Animal studies also demonstrate that flavonoid supplementation may alleviate neurodegenerative cognitive and memory impairments. Limited human studies, however, demonstrate the need for further clinical research investigating flavonoids. Flavonoid supplementation, as well as dietary modification to include whole foods high in flavonoids, may provide therapeutic potential for aging individuals experiencing cognitive deficits resulting from neurodegeneration.

HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.

PubMed

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

Aging and cognition.

PubMed

Mather, Mara

2010-05-01

As we grow older, we gain knowledge and experience greater emotional balance, but we also experience memory loss and difficulties in learning new associations. Which cognitive abilities decline, remain stable or improve with age depends on the health of the brain and body as well as on what skills are practiced or challenged in everyday life. Recent research provides a growing understanding of the relationship between physical and cognitive changes across the life span and reveals ways to increase mental sharpness and avoid cognitive decline. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website. Copyright © 2010 John Wiley & Sons, Ltd.

Do apolipoprotein E genotype and educational attainment predict the rate of cognitive decline in normal aging? A 12-year follow-up of the Maastricht Aging Study.

PubMed

Van Gerven, Pascal W M; Van Boxtel, Martin P J; Ausems, Eleonora E B; Bekers, Otto; Jolles, Jelle

2012-07-01

We investigated suspected longitudinal interaction effects of apolipoprotein E (APOE) genotype and educational attainment on cognitive decline in normal aging. Our sample consisted of 571 healthy, nondemented adults aged between 49 and 82 years. Linear mixed-models analyses were performed with four measurement time points: baseline, 3-year, 6-year, and 12-year follow-up. Covariates included age at baseline, sex, and self-perceived physical and mental health. Dependent measures were global cognitive functioning (Mini-Mental State Examination; Folstein, Folstein, & McHugh, 1975), Stroop performance (Stroop Color-Word Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006a), set-shifting performance (Concept Shifting Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006b), cognitive speed (Letter-Digit Substitution Test; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2006c), verbal learning (Verbal Learning Test: Sum of five trials; Van der Elst, Van Boxtel, Van Breukelen, & Jolles, 2005), and long-term memory (Verbal Learning Test: Delayed recall). We found only faint evidence that older, high-educated carriers of the APOE-ε4 allele (irrespective of zygosity) show a more pronounced decline than younger, low-educated carriers and noncarriers (irrespective of educational attainment). Moreover, this outcome was confined to concept-shifting performance and was especially observable between 6- and 12-year follow-ups. No protective effects of higher education were found on any of the six cognitive measures. We conclude that the combination of APOE-ε4 allele and high educational attainment may be a risk factor for accelerated cognitive decline in older age, as has been reported before, but only to a very limited extent. Moreover, we conclude that, within the cognitive reserve framework, education does not have significant protective power against age-related cognitive decline.

AGED DOMINANT NEGATIVE p38α MAPK MICE ARE RESISTANT TO AGE-DEPENDENT DECLINE IN ADULT-NEUROGENESIS AND CONTEXT DISCRIMINATION FEAR CONDITIONING

PubMed Central

Cortez, IbDanelo; Bulavin, Dmitry V.; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

2018-01-01

A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38αAF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38αAF/+) and kinase activity. As a result, aged DN-p38αAF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer’s disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual’s relative risk. In the present study, we evaluated aged DN-p38αAF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38αAF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38αAF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38αAF/+, we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38αAF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. PMID:27765672

Aged dominant negative p38α MAPK mice are resistant to age-dependent decline in adult-neurogenesis and context discrimination fear conditioning.

PubMed

Cortez, IbDanelo; Bulavin, Dmitry V; Wu, Ping; McGrath, Erica L; Cunningham, Kathryn A; Wakamiya, Maki; Papaconstantinou, John; Dineley, Kelly T

2017-03-30

A major aspect of mammalian aging is the decline in functional competence of many self-renewing cell types, including adult-born neuronal precursors. Since age-related senescence of self-renewal occurs simultaneously with chronic up-regulation of the p38MAPKalpha (p38α) signaling pathway, we used the dominant negative mouse model for attenuated p38α activity (DN-p38α AF/+ ) in which Thr180 and Tyr182 are mutated (T→A/Y→F) to prevent phosphorylation activation (DN-p38α AF/+ ) and kinase activity. As a result, aged DN-p38α AF/+ mice are resistant to age-dependent decline in proliferation and regeneration of several peripheral tissue progenitors when compared to wild-type littermates. Aging is the major risk factor for non-inherited forms of Alzheimer's disease (AD); environmental and genetic risk factors that accelerate the senescence phenotype are thought to contribute to an individual's relative risk. In the present study, we evaluated aged DN-p38α AF/+ and wildtype littermates in a series of behavioral paradigms to test if p38α mutant mice exhibit altered baseline abnormalities in neurological reflexes, locomotion, anxiety-like behavior, and age-dependent cognitive decline. While aged DN-p38α AF/+ and wildtype littermates appear equal in all tested baseline neurological and behavioral parameters, DN-p38α AF/+ exhibit superior context discrimination fear conditioning. Context discrimination is a cognitive task that is supported by proliferation and differentiation of adult-born neurons in the dentate gyrus of the hippocampus. Consistent with enhanced context discrimination in aged DN-p38α AF/+ , we discovered enhanced production of adult-born neurons in the dentate gyrus of DN-p38α AF/+ mice compared to wildtype littermates. Our findings support the notion that p38α inhibition has therapeutic utility in aging diseases that affect cognition, such as AD. Copyright © 2016 Elsevier B.V. All rights reserved.

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…

Visual Search Load Effects on Age-Related Cognitive Decline: Evidence From the Yakumo Longitudinal Study.

PubMed

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.

Food for thought: the role of appetitive peptides in age-related cognitive decline.

PubMed

Fadel, Jim R; Jolivalt, Corinne G; Reagan, Lawrence P

2013-06-01

Through their well described actions in the hypothalamus, appetitive peptides such as insulin, orexin and leptin are recognized as important regulators of food intake, body weight and body composition. Beyond these metabolic activities, these peptides also are critically involved in a wide variety of activities ranging from modulation of immune and neuroendocrine function to addictive behaviors and reproduction. The neurological activities of insulin, orexin and leptin also include facilitation of hippocampal synaptic plasticity and enhancement of cognitive performance. While patients with metabolic disorders such as obesity and diabetes have greater risk of developing cognitive deficits, dementia and Alzheimer's disease (AD), the underlying mechanisms that are responsible for, or contribute to, age-related cognitive decline are poorly understood. In view of the importance of these peptides in metabolic disorders, it is not surprising that there is a greater focus on their potential role in cognitive deficits associated with aging. The goal of this review is to describe the evidence from clinical and pre-clinical studies implicating insulin, orexin and leptin in the etiology and progression of age-related cognitive decline. Collectively, these studies support the hypothesis that leptin and insulin resistance, concepts normally associated with the hypothalamus, are also applicable to the hippocampus. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

NASA Astrophysics Data System (ADS)

Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

2016-08-01

In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

Does Stroke Contribute to Racial Differences in Cognitive Decline?

PubMed Central

Levine, Deborah A.; Kabeto, Mohammed; Langa, Kenneth M.; Lisabeth, Lynda D.; Rogers, Mary A.M.; Galecki, Andrzej T.

2015-01-01

Background and Purpose It is unknown whether blacks’ elevated risk of dementia is because of racial differences in acute stroke, the impact of stroke on cognitive health, or other factors. We investigated whether racial differences in cognitive decline are explained by differences in the frequency or impact of incident stroke between blacks and whites, controlling for baseline cognition. Methods Among 4908 black and white participants aged ≥65 years free of stroke and cognitive impairment in the nationally representative Health and Retirement Study with linked Medicare data (1998–2010), we examined longitudinal changes in global cognition (modified version of the Telephone Interview for Cognitive Status) by race, before and after adjusting for time-dependent incident stroke followed by a race-by-incident stroke interaction term, using linear mixed-effects models that included fixed effects of participant demographics, clinical factors, and cognition, and random effects for intercept and slope for time. Results We identified 34 of 453 (7.5%) blacks and 300 of 4455 (6.7%) whites with incident stroke over a mean (SD) of 4.1 (1.9) years of follow-up (P=0.53). Blacks had greater cognitive decline than whites (adjusted difference in modified version of the Telephone Interview for Cognitive Status score, 1.47 points; 95% confidence interval, 1.21 to 1.73 points). With further adjustment for cumulative incidence of stroke, the black–white difference in cognitive decline persisted. Incident stroke was associated with a decrease in global cognition (1.21 points; P<0.001) corresponding to ≈7.9 years of cognitive aging. The effect of incident stroke on cognition did not statistically differ by race (P=0.52). Conclusions In this population-based cohort of older adults, incident stroke did not explain black–white differences in cognitive decline or impact cognition differently by race. PMID:25999389

The relationship of bilingualism to cognitive decline: The Australian Longitudinal Study of Ageing.

PubMed

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.

Metal chaperones prevent zinc-mediated cognitive decline.

PubMed

Adlard, Paul A; Parncutt, Jacqui; Lal, Varsha; James, Simon; Hare, Dominic; Doble, Philip; Finkelstein, David I; Bush, Ashley I

2015-09-01

Zinc transporter-3 (ZnT3) protein is responsible for loading zinc into presynaptic vesicles and consequently controls the availability of zinc at the glutamatergic synapse. ZnT3 has been shown to decline with age and in Alzheimer's disease (AD) and is crucially involved in learning and memory. In this study, we utilised whole animal behavioural analyses in the ZnT3 KO mouse line, together with electrophysiological analysis of long-term potentiation in brain slices from ZnT3 KO mice, to show that metal chaperones (clioquinol, 30 mg/kg/day for 6weeks) can prevent the age-dependent cognitive phenotype that characterises these animals. This likely occurs as a result of a homeostatic restoration of synaptic protein expression, as clioquinol significantly restored levels of various pre- and postsynaptic proteins that are critical for normal cognition, including PSD-95; AMPAR and NMDAR2b. We hypothesised that this clioquinol-mediated restoration of synaptic health resulted from a selective increase in synaptic zinc content within the hippocampus. While we demonstrated a small regional increase in hippocampal zinc content using synchrotron x-ray fluorescence microscopy, further sub-region analyses are required to determine whether this effect is seen in other regions of the hippocampal formation that are more closely linked to the synaptic plasticity effects observed in this study. These data support our recent report on the use of a different metal chaperone (PBT2) to prevent normal age-related cognitive decline and demonstrate that metal chaperones are efficacious in preventing the zinc-mediated cognitive decline that characterises ageing and disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Meditation and successful aging: can meditative practices counteract age-related cognitive decline?

PubMed

Sperduti, Marco; Makowski, Dominique; Blondé, Philippe; Piolino, Pascale

2017-06-01

Life expectancy is constantly increasing in the developed countries due to medical, hygiene and socio-economic advances. Unfortunately, a longer life not always corresponds to a healthier life. Indeed, aging is associated with growing risk factors for illness associated with societal conditions (isolation, maltreatment), and neurodegenerative diseases. Even normal aging is associated with a cognitive decline that can hinder independence and quality of life of elderly. Thus, one major societal challenge is to build policies that support people of all ages to maintain a maximum health and functional capacity throughout their lives. Meditation could be a promising intervention in contrasting the negative effects of aging. Indeed, it has been shown to enhance cognitive efficiency in several domains, such as attention and executive functions in young adults. Nevertheless, whether these effects extend to old participants is still a matter of debate. Few studies have directly investigated this issue, reporting encouraging results in a large panel of cognitive functions, such as: attention, executive functions and memory. However, a final conclusion about the causal role of meditation and the generalization of these results is made difficult due to several methodological limitations. We propose a roadmap for future studies to pass these limitations with the hope that the present work would contribute to the development of the young research field of meditation in gerontology.

Enriched childhood experiences moderate age-related motor and cognitive decline

PubMed Central

Metzler, Megan J.; Saucier, Deborah M.; Metz, Gerlinde A.

2012-01-01

Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks. PMID:23423702

Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

PubMed

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.

Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review

PubMed Central

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

Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study.

PubMed

Zahodne, Laura B; Glymour, M Maria; Sparks, Catharine; Bontempo, Daniel; Dixon, Roger A; MacDonald, Stuart W S; Manly, Jennifer J

2011-11-01

Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging.

Age-related cognitive decline as a function of daytime testing.

PubMed

Puiu, Andrei Alexandru

2017-05-01

The current study investigates the effects of age, cognitive load, optimal time-of-day testing, and irrelevant background noise suppression on mental processing. One hundred and seventy-eight young (M = 22.97 years) and 114 old adults (M = 56.38 years) were assessed for implicit learning and speed of information processing under irrelevant sound interference early during daytime (7AM-2.30PM) or in the afternoons (3PM-midnight). No direct effect of irrelevant speech effect was found on implicit learning. An optimal time of testing per age group was identified according to the ability to suppress irrelevant auditory information. If no semantic meaning was derived from the sound conditions, irrelevant sound was easily inhibited leaving no room for declined cognitive performance. This suggests an intact phonological inhibition in older adults and a further circumvention of the phonological loop. However, when difficulty was increased, a widened performance gap between young and old people could be observed. Education modulated difficult performance irrespective of age. With increasing age, task demand fulfillment becomes a function of a limited time mechanism. If extraneous time is not adapted to cognitive skills and performance, higher order processing cannot be reached, rendering older adults slower than their younger counterparts.

β-Secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice

PubMed Central

Chang, Wan-Pin; Huang, Xiangping; Downs, Deborah; Cirrito, John R.; Koelsch, Gerald; Holtzman, David M.; Ghosh, Arun K.; Tang, Jordan

2011-01-01

Alzheimer disease is intimately linked to an excess amount of amyloid-β (Aβ) in the brain. Thus, therapeutic inhibition of Aβ production is an attractive clinical approach to treat this disease. Here we provide the first direct experimental evidence that the treatment of Tg2576 transgenic mice with an inhibitor of β-secretase, GRL-8234, rescues the age-related cognitive decline. We demonstrated that the injected GRL-8234 effectively enters the brain and rapidly decreases soluble Aβ in the brain of Tg2576 mice. The rescue of cognition, which was observed only after long-term inhibitor treatment ranging from 5 to 7.5 mo, was associated with a decrease of brain amyloid-β plaque load. We also found no accumulation of amyloid-β precursor protein after several months of inhibitor treatment. These observations substantiate the idea that Aβ accumulation plays a major role in the cognitive decline of Tg2576 mice and support the concept of Aβ reduction therapy as a treatment of AD.—Chang, W.-P., Huang, X., Downs, D., Cirrito, J. R., Koelsch, G., Holtzman, D. M. Ghosh, A. K., Tang, J. β-Secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice. PMID:21059748

Thinner cortex in patients with subjective cognitive decline is associated with steeper decline of memory.

PubMed

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.

Positive affect and cognitive decline: a 12-year follow-up of the Maastricht Aging Study.

PubMed

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.

Occupational cognitive requirements and late-life cognitive aging.

PubMed

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.

Stressful life events and cognitive decline in late life: moderation by education and age. The Cache County Study.

PubMed

Tschanz, Joann T; Pfister, Roxane; Wanzek, Joseph; Corcoran, Chris; Smith, Ken; Tschanz, Brian T; Steffens, David C; Østbye, Truls; Welsh-Bohmer, Kathleen A; Norton, Maria C

2013-08-01

Stressful life events (SLE) have been associated with increased dementia risk, but their association with cognitive decline has been inconsistent. In a longitudinal population-based study of older individuals, we examined the association between SLE and cognitive decline, and the role of potential effect modifiers. A total of 2665 non-demented participants of the Cache County Memory Study completed an SLE questionnaire at Wave 2 and were revisited 4 and 7 years later. The events were represented via several scores: total number, subjective rating (negative, positive, and unexpected), and a weighted summary based on their impact. Cognition was assessed at each visit with the modified Mini-Mental State Exam. General linear models were used to examine the association between SLE scores and cognition. Effect modification by age, education, and APOE genotype was tested. Years of formal education (p = 0.006) modified the effect of number of SLE, and age (p = 0.009) modified the effect of negative SLE on the rate of cognitive decline. Faster decline was observed among those with fewer years of education experiencing more SLE and also among younger participants experiencing more negative SLE. There was no association between other indicators of SLE and cognitive decline. APOE genotype did not modify any of the aforementioned associations. The effects of SLE on cognition in late life are complex and vary by individual factors such as age and education. These results may explain some of the contradictory findings in the literature. Copyright © 2012 John Wiley & Sons, Ltd.

Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

PubMed

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/

C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

USDA-ARS?s Scientific Manuscript database

Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) tri...

BioAge: Toward A Multi-Determined, Mechanistic Account of Cognitive Aging

PubMed Central

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

Efficacy of curcumin for age-associated cognitive decline: a narrative review of preclinical and clinical studies.

PubMed

Sarker, Marjana Rahman; Franks, Susan F

2018-04-21

Processes such as aberrant redox signaling and chronic low-grade systemic inflammation have been reported to modulate age-associated pathologies such as cognitive impairment. Curcumin, the primary therapeutic component of the Indian spice, Turmeric (Curcuma longa), has long been known for its strong anti-inflammatory and antioxidant activity attributable to its unique molecular structure. Recently, an interest in this polyphenol as a cognitive therapeutic for the elderly has emerged. The purpose of this paper is to critically review preclinical and clinical studies that have evaluated the efficacy of curcumin in ameliorating and preventing age-associated cognitive decline and address the translational progress of preclinical to clinical efficacy. PubMed, semantic scholar, and Google scholar searches were used for preclinical studies; and clinicaltrials.gov , the Australian and New Zealand clinical trials registry, and PubMed search were used to select relevant completed clinical studies. Results from preclinical studies consistently demonstrate curcumin and its analogues to be efficacious for various aspects of cognitive impairment and processes that contribute to age-associated cognitive impairment. Results of published clinical studies, while mixed, continue to show promise for curcumin's use as a therapeutic for cognitive decline but overall remain inconclusive at this time. Both in vitro and in vivo studies have found that curcumin can significantly decrease oxidative stress, systemic inflammation, and obstruct pathways that activate transcription factors that augment these processes. Future clinical studies would benefit from including evaluation of peripheral and cerebrospinal fluid biomarkers of dementia and behavioral markers of cognitive decline, as well as targeting the appropriate population.

Complexity and Synchronicity of Resting State BOLD FMRI in Normal Aging and Cognitive Decline

PubMed Central

Liu, Collin Y; Krishnan, Anitha P; Yan, Lirong; Smith, Robert X; Kilroy, Emily; Alger, Jeffery R; Ringman, John M; Wang, Danny JJ

2012-01-01

Purpose To explore the use of approximate entropy (ApEn) as an index of the complexity and the synchronicity of resting state BOLD fMRI in normal aging and cognitive decline associated with familial Alzheimer’s disease (fAD). Materials and Methods Resting state BOLD fMRI data were acquired at 3T from 2 independent cohorts of subjects consisting of healthy young (age 23±2 years, n=8) and aged volunteers (age 66±3 years, n=8), as well as 22 fAD associated subjects (14 mutation carriers, age 41.2±15.8 years; and 8 non-mutation carrying family members, age 28.8±5.9 years). Mean ApEn values were compared between the two age groups, and correlated with cognitive performance in the fAD group. Cross-ApEn (C-ApEn) was further calculated to assess the asynchrony between precuneus and the rest of the brain. Results Complexity of brain activity measured by mean ApEn in gray and white matter decreased with normal aging. In the fAD group, cognitive impairment was associated with decreased mean ApEn in gray matter as well as decreased regional ApEn in right precuneus, right lateral parietal regions, left precentral gyrus, and right paracentral gyrus. A pattern of asynchrony between BOLD fMRI series emerged from C-ApEn analysis, with significant regional anti-correlation with cross-correlation coefficient of functional connectivity analysis. Conclusion ApEn and C-ApEn may be useful for assessing the complexity and synchronicity of brain activity in normal aging and cognitive decline associated with neurodegenerative diseases PMID:23225622

Late Life Leisure Activities and Risk of Cognitive Decline

PubMed Central

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

Early-life Infection is a Vulnerability Factor for Aging-Related Glial Alterations and Cognitive Decline

PubMed Central

Bilbo, Staci D.

2010-01-01

There is significant individual variability in cognitive decline during aging, suggesting the existence of “vulnerability factors” for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or E. coli, and then tested for learning & memory at 2 or 16 month of age, using 2 fear conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16 month. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHC II on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity. PMID:20388544

Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.

PubMed

Bilbo, Staci D

2010-07-01

There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.

Decline in Weight and Incident Mild Cognitive Impairment: Mayo Clinic Study of Aging

PubMed Central

Alhurani, Rabe E.; Vassilaki, Maria; Aakre, Jeremiah; Mielke, Michelle M.; Kremers, Walter K.; Machulda, Mary M.; Geda, Yonas E.; Knopman, David S.; Peterson, Ronald C.; Roberts, Rosebud O.

2016-01-01

IMPORTANCE Unintentional weight loss has been associated with risk of dementia. Since mild cognitive impairment (MCI) is a prodromal stage for dementia, we sought to evaluate whether changes in weight and body mass index (BMI) may predict incident MCI. OBJECTIVE To investigate the association of change in weight and BMI with risk of MCI. DESIGN, SETTING, AND PARTICIPANTS A population-based, prospective study of participants aged 70 years and older from the Mayo Clinic Study of Aging. Maximum weight and height in midlife (aged 40 to 65 years old) were retrospectively ascertained from the medical records of participants using a medical records linkage system. MAIN OUTCOMES MEASURES Participants were evaluated for cognitive outcomes of normal cognition, MCI, or dementia at baseline and prospectively assessed for incident events at each 15-month evaluation. The association of rate of change in weight and body mass index with risk of MCI was investigated using proportional hazards models. RESULTS Over a mean follow-up of 4.4 years, 524 of 1895 cognitively normal participants developed incident MCI. The mean (standard deviation) rate of weight change per decade from midlife to study entry was greater for individuals who developed incident MCI vs. those who remained cognitively normal (−2.0 (5.1) vs. −1.2 (4.9) kg; p = 0.006). A greater decline in weight per decade was associated with an increased risk of incident MCI (hazard ratio [HR] 95% confidence interval [CI], 1.04 [1.02, 1.06], p < 0.001) after adjusting for sex, education and apolipoprotein E (APOE) ε4 allele. A weight loss of 5 kg/decade corresponds to a 24% increase in risk of MCI (HR=1.24). Higher decline in BMI per decade was also associated with incident MCI (HR, 1.08, 95% CI = [1.03, 1.13], p = 0.003). CONCLUSIONS AND RELEVANCE These findings suggest that declining weight from midlife to late-life is a marker for MCI and may help identify persons at increased risk for MCI. PMID:26831542

Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing.

PubMed

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.

BioAge: toward a multi-determined, mechanistic account of cognitive aging.

PubMed

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.

Memory complaints and APOE-epsilon4 accelerate cognitive decline in cognitively normal elderly.

PubMed

Dik, M G; Jonker, C; Comijs, H C; Bouter, L M; Twisk, J W; van Kamp, G J; Deeg, D J

2001-12-26

To investigate to what extent subjective memory complaints and APOE-epsilon4 allele carriage predict future cognitive decline in cognitively intact elderly persons, by evaluating both their separate and combined effects. We selected 1,168 subjects from the population-based Longitudinal Aging Study Amsterdam who were 62 to 85 years of age and had no obvious cognitive impairment at baseline (Mini-Mental State Examination [MMSE] score, > or =27). Memory complaints and APOE phenotypes were assessed at baseline. MMSE, the Auditory Verbal Learning Test (memory: immediate recall and delayed recall), and the Alphabet Coding Task-15 (information processing speed) were used to study cognitive decline. Follow-up data were collected after 3 and 6 years. Data were analyzed with generalized estimating equations, adjusted for age, sex, education, and depression. Baseline memory complaints were reported by 25.5% of the cognitively intact elderly persons. Overall, 25.3% of the subjects were carriers of at least one APOE-epsilon4 allele. Memory complaints were associated with a greater rate of decline in all cognitive measures, except immediate recall. In addition, APOE-epsilon4 allele carriers had a greater rate of cognitive decline shown by MMSE scores and slower information processing speeds after 6 years. The effects of both memory complaints and APOE-epsilon4 allele carriage were additive: subjects with both factors had a two times higher cognitive decline than did subjects without both factors. Both memory complaints and APOE-epsilon4 allele carriage predict cognitive decline at an early stage. This finding highlights the importance of subjective memory complaints, which are important even at an early stage when objective tests are still unable to detect cognitive deficits and are especially important for elderly carriers of the APOE-epsilon4 allele because they have an additional risk.

Longitudinal Attentional Engagement Rescues Mice from Age-Related Cognitive Declines and Cognitive Inflexibility

ERIC Educational Resources Information Center

Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

2011-01-01

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…

Age-related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice.

PubMed

Reichel, J M; Bedenk, B T; Czisch, M; Wotjak, C T

2017-01-01

Even in the absence of neurodegenerative diseases, progressing age often coincides with cognitive decline and morphological changes. However, longitudinal studies that directly link these two processes are missing. In this proof-of-concept study we therefore performed repeated within-subject testing of healthy male R26R mice in a spatial learning task in combination with manganese-enhanced volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice into good and poor performers (n = 6, each), based on their spatial learning abilities at the age of 24 months. Using this stratification, we failed to detect a priori volume differences, but observed a significant decrease in total hippocampal volume over time for both groups. Interestingly, this volume decrease was specific for the dorsal hippocampus and significantly accelerated in poor performers between 16 and 24 months of age. This is the first time that individual changes in hippocampal volume were traced alongside cognitive performance within the same subjects over 1½ years. Our study points to a causal link between volume loss of the dorsal hippocampus and cognitive impairments. In addition, it suggests accelerated degenerative processes rather than a priori volume differences as determining trajectories of age-related cognitive decline. Despite the relatively small sample sizes, the strong behavioral and moderate morphological alterations demonstrate the general feasibility of longitudinal studies of age-related decline in cognition and hippocampus integrity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neuroanatomical Substrates of Age-Related Cognitive Decline

ERIC Educational Resources Information Center

Salthouse, Timothy A.

2011-01-01

There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

Effects of head circumference and metabolic syndrome on cognitive decline.

PubMed

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.

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

PubMed

Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

2017-09-01

Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Strategies for Preventing Cognitive Decline in Healthy Older Adults

PubMed Central

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

Association between age associated cognitive decline and health related quality of life among Iranian older individuals.

PubMed

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.

Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease.

PubMed

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.

Education and Cognitive Decline in Older Americans: Results From the AHEAD Sample

PubMed Central

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

Protective Role of Recent and Past Long-Term Physical Activity on Age-Related Cognitive Decline: The Moderating Effect of Sex.

PubMed

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.

High blood pressure and cognitive decline in mild cognitive impairment.

PubMed

Goldstein, Felicia C; Levey, Allan I; Steenland, N Kyle

2013-01-01

To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains. Prospective longitudinal cohort. Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers. One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits. Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score. Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score. Hypertension is associated with faster cognitive decline in persons at risk for dementia. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

High Blood Pressure and Cognitive Decline in Mild Cognitive Impairment

PubMed Central

Goldstein, Felicia C.; Levey, Allan I.; Steenland, N. Kyle

2013-01-01

Objectives To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains. Design Prospective longitudinal cohort. Setting Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers. Participants One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits. Measurements Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score. Results Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score. Conclusion Hypertension is associated with faster cognitive decline in persons at risk for dementia. PMID:23301925

Decline in cognitive function and risk of elder self-neglect: finding from the Chicago Health Aging Project.

PubMed

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.

Mediterranean Diet and Age-Related Cognitive Decline: A Randomized Clinical Trial.

PubMed

Valls-Pedret, Cinta; Sala-Vila, Aleix; Serra-Mir, Mercè; Corella, Dolores; de la Torre, Rafael; Martínez-González, Miguel Ángel; Martínez-Lapiscina, Elena H; Fitó, Montserrat; Pérez-Heras, Ana; Salas-Salvadó, Jordi; Estruch, Ramon; Ros, Emilio

2015-07-01

Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1, 2003, through December 31, 2009. All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study. Participants were randomly assigned to a Mediterranean diet supplemented with extravirgin olive oil (1 L/wk), a Mediterranean diet supplemented with mixed nuts (30 g/d), or a control diet (advice to reduce dietary fat). Rates of cognitive change over time based on a neuropsychological test battery: Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT), Animals Semantic Fluency, Digit Span subtest from the Wechsler Adult Intelligence Scale, Verbal Paired Associates from the Wechsler Memory Scale, and the Color Trail Test. We used mean z scores of change in each test to construct 3 cognitive composites: memory, frontal (attention and executive function), and global. Follow-up cognitive tests were available in 334 participants after intervention (median, 4.1 years). In multivariate analyses adjusted for confounders, participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT (P = .049) and Color Trail Test part 2 (P = .04) compared with controls; no between-group differences were observed for the other cognitive tests

Neighborhood socioeconomic context and cognitive decline among older Mexican Americans: results from the Sacramento Area Latino Study on Aging.

PubMed

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.

Normal cognitive decline or dementia?

PubMed

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.

Frontotemporal dysregulation of the SNARE protein interactome is associated with faster cognitive decline in old age.

PubMed

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

Cognitive declines in healthy aging: evidence from multiple aspects of interference resolution.

PubMed

Pettigrew, Corinne; Martin, Randi C

2014-06-01

The present study tested the hypothesis that older adults show age-related deficits in interference resolution, also referred to as inhibitory control. Although oftentimes considered as a unitary aspect of executive function, various lines of work support the notion that interference resolution may be better understood as multiple constructs, including resistance to proactive interference (PI) and response-distractor inhibition (e.g., Friedman & Miyake, 2004). Using this dichotomy, the present study assessed whether older adults (relative to younger adults) show impaired performance across both, 1, or neither of these interference resolution constructs. To do so, we used multiple tasks to tap each construct and examined age effects at both the single task and latent variable levels. Older adults consistently demonstrated exaggerated interference effects across resistance to PI tasks. Although the results for the response-distractor inhibition tasks were less consistent at the individual task level analyses, age effects were evident on multiple tasks, as well as at the latent variable level. However, results of the latent variable modeling suggested declines in interference resolution are best explained by variance that is common to the 2 interference resolution constructs measured herein. Furthermore, the effect of age on interference resolution was found to be both distinct from declines in working memory, and independent of processing speed. These findings suggest multiple cognitive domains are independently sensitive to age, but that declines in the interference resolution constructs measured herein may originate from a common cause. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease

PubMed Central

Aguirre-Acevedo, Daniel C.; Lopera, Francisco; Henao, Eliana; Tirado, Victoria; Muñoz, Claudia; Giraldo, Margarita; Bangdiwala, Shrikant I.; Reiman, Eric M.; Tariot, Pierre N.; Langbaum, Jessica B.; Quiroz, Yakeel T.; Jaimes, Fabian

2017-01-01

IMPORTANCE Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. OBJECTIVES To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. MAIN OUTCOMES AND MEASURES Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline. RESULTS A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred’s respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

PubMed Central

Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

2011-01-01

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement. PMID:21521768

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility.

PubMed

Matzel, Louis D; Light, Kenneth R; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C; Kolata, Stefan

2011-01-01

Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.

Cognitive decline following incident and preexisting diabetes mellitus in a population sample.

PubMed

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.

An Examination of Age-Based Stereotype Threat About Cognitive Decline.

PubMed

Barber, Sarah J

2017-01-01

"Stereotype threat" is often thought of as a singular construct, with moderators and mechanisms that are stable across groups and domains. However, this is not always true. To illustrate this, the current review focuses on the stereotype threat that older adults face about their cognitive abilities. Drawing upon the multithreat framework, I first provide evidence that this is a self-concept threat and not a group-reputation threat. Because this differs from the forms of stereotype threat experienced by other groups (e.g., the threat that minority students face about their intellectual abilities), the moderators of stereotype threat observed in other groups (i.e., group identification) do not always generalize to age-based stereotype threat about cognitive decline. Looking beyond the forms of stereotype threat elicited, this review also provides evidence that the mechanisms underlying stereotype-threat effects may vary across the adult life span. Because of age-related improvements in emotion-regulation abilities, stereotype threat does not seem to reduce older adults' executive-control resources. Overall, this review highlights the need to approach the concept of stereotype threat with more granularity, allowing researchers to design more effective stereotype-threat interventions. It will also shed light on why certain stereotype threat effects "fail to replicate" across domains or groups.

Cognitive Decline and Its Risk Factors in Prevalent Hemodialysis Patients.

PubMed

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

Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

PubMed Central

Gerstorf, Denis; Ram, Nilam; Hoppmann, Christiane; Willis, Sherry L.; Schaie, K. Warner

2011-01-01

Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort differences in the rate of cognitive aging and if, at the very end of life, pervasive mortality-related processes overshadow and minimize cohort differences. We used data on 5 primary mental abilities from the Seattle Longitudinal Study (Schaie, 2005) to compare both age-related and mortality-related changes between earlier born cohorts (1886–1913) and later born cohorts (1914–1948). Our models covary for several individual and cohort differences in central indicators of life expectancy, education, health, and gender. Age-related growth models corroborate and extend earlier findings by documenting level differences at age 70 of up to 0.50 SD and less steep rates of cognitive aging on all abilities between 50 and 80 years of age favoring the later born cohort. In contrast, mortality-related models provide limited support for positive cohort differences. The later born cohort showed steeper mortality-related declines. We discuss possible reasons why often reported positive secular trends in age-related processes may not generalize to the vulnerable segment of the population that is close to death and suggest routes for further inquiry. PMID:21517155

Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging

PubMed Central

Gold, Brian T.; Johnson, Nathan F.; Powell, David K.

2013-01-01

Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N = 20) and monolinguals (N = 20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging. PMID:24103400

Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly--Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe).

PubMed

Roehr, Susanne; Luck, Tobias; Heser, Kathrin; Fuchs, Angela; Ernst, Annette; Wiese, Birgitt; Werle, Jochen; Bickel, Horst; Brettschneider, Christian; Koppara, Alexander; Pentzek, Michael; Lange, Carolin; Prokein, Jana; Weyerer, Siegfried; Mösch, Edelgard; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin; Jessen, Frank; Riedel-Heller, Steffi G

2016-01-01

Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer's disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8-1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7-1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

Fibrillar amyloid correlates of preclinical cognitive decline.

PubMed

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.

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study.

PubMed

Lipnicki, Darren M; Crawford, John D; Dutta, Rajib; Thalamuthu, Anbupalam; Kochan, Nicole A; Andrews, Gavin; Lima-Costa, M Fernanda; Castro-Costa, Erico; Brayne, Carol; Matthews, Fiona E; Stephan, Blossom C M; Lipton, Richard B; Katz, Mindy J; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C W; Wong, Candy H Y; Fung, Ada W T; Guaita, Antonio; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Anstey, Kaarin J; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Ng, Tze Pin; Gao, Qi; Reppermund, Simone; Brodaty, Henry; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S

2017-03-01

The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p

Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

PubMed Central

Lipnicki, Darren M.; Crawford, John D.; Thalamuthu, Anbupalam; Castro-Costa, Erico; Stephan, Blossom C. M.; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C. W.; Fung, Ada W. T.; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S.

2017-01-01

Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0

Subjective Cognitive Decline, Objective Cognition, and Depression in Older Hispanics Screened for Memory Impairment.

PubMed

Zlatar, Zvinka Z; Muniz, Martha C; Espinoza, Sarah G; Gratianne, Roberto; Gollan, Tamar H; Galasko, Douglas; Salmon, David P

2018-01-01

Subjective cognitive decline (SCD) is common in older adults and may be an early marker of future cognitive decline. Research suggest that SCD is more closely related to concurrent symptoms of depression than to objective cognitive performance in non-Hispanic Whites, but it is unknown whether the associations of SCD, cognition, and depression manifest differently in Hispanic older adults. We examined if SCD is associated with objective cognitive performance or with depression symptoms in 145 Hispanic individuals ages 60 or older referred by community health clinics for screening of cognitive complaints. All participants lived near the U.S.-Mexico border, spoke Spanish only, or were Spanish-English bilingual. Memory-only and global cognitive composites were created from scores on Spanish versions of several neuropsychological tests. The Geriatric Depression Scale (GDS) and a five-item SCD questionnaire developed by our group were also completed. Multiple regression analyses showed no significant associations between SCD and memory or global cognitive composite scores after adjusting for age, sex, education, and GDS score. In contrast, there was a significant association between GDS and SCD after adjusting for age, sex, education, global and memory composite scores. Findings suggest that SCD does not accurately reflect current cognitive status in older Hispanics who present to their primary care physician with cognitive complaints. Clinicians should interpret SCD in this population within the context of information about symptoms of depression. Longitudinal research is needed in older Hispanics to better characterize SCD in this population and to determine if it can predict future cognitive decline.

Distinct Aging Effects on Functional Networks in Good and Poor Cognitive Performers

PubMed Central

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

A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer's disease.

PubMed

Mostafavi, Sara; Gaiteri, Chris; Sullivan, Sarah E; White, Charles C; Tasaki, Shinya; Xu, Jishu; Taga, Mariko; Klein, Hans-Ulrich; Patrick, Ellis; Komashko, Vitalina; McCabe, Cristin; Smith, Robert; Bradshaw, Elizabeth M; Root, David E; Regev, Aviv; Yu, Lei; Chibnik, Lori B; Schneider, Julie A; Young-Pearse, Tracy L; Bennett, David A; De Jager, Philip L

2018-06-01

There is a need for new therapeutic targets with which to prevent Alzheimer's disease (AD), a major contributor to aging-related cognitive decline. Here we report the construction and validation of a molecular network of the aging human frontal cortex. Using RNA sequence data from 478 individuals, we first build a molecular network using modules of coexpressed genes and then relate these modules to AD and its neuropathologic and cognitive endophenotypes. We confirm these associations in two independent AD datasets. We also illustrate the use of the network in prioritizing amyloid- and cognition-associated genes for in vitro validation in human neurons and astrocytes. These analyses based on unique cohorts enable us to resolve the role of distinct cortical modules that have a direct effect on the accumulation of AD pathology from those that have a direct effect on cognitive decline, exemplifying a network approach to complex diseases.

Disparities in Age-Associated Cognitive Decline Between African-American and Caucasian Populations: The Roles of Health Literacy and Education.

PubMed

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.

Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

PubMed Central

Febo, Marcelo; Foster, Thomas C.

2016-01-01

Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer's disease.

PubMed

Harrison, Fiona E

2012-01-01

Antioxidants in the diet have long been thought to confer some level of protection against the oxidative damage that is involved in the pathology of Alzheimer's disease as well as general cognitive decline in normal aging. Nevertheless, support for this hypothesis in the literature is equivocal. In the case of vitamin C (ascorbic acid) in particular, lack of consideration of some of the specific features of vitamin C metabolism has led to studies in which classification of participants according to vitamin C status is inaccurate, and the absence of critical information precludes the drawing of appropriate conclusions. Vitamin C levels in plasma are not always reported, and estimated daily intake from food diaries may not be accurate or reflect actual plasma values. The ability to transport ingested vitamin C from the intestines into blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1) and thus very high intakes and the use of supplements are often erroneously considered to be of greater benefit that they really are. The current review documents differences among the studies in terms of vitamin C status of participants. Overall, there is a large body of evidence that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and Alzheimer's disease, but avoiding vitamin C deficiency is likely to be more beneficial than taking supplements on top of a normal, healthy diet.

Poor Decision Making Is a Consequence of Cognitive Decline among Older Persons without Alzheimer’s Disease or Mild Cognitive Impairment

PubMed Central

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

Video Games as a Means to Reduce Age-Related Cognitive Decline: Attitudes, Compliance, and Effectiveness

PubMed Central

Boot, Walter R.; Champion, Michael; Blakely, Daniel P.; Wright, Timothy; Souders, Dustin J.; Charness, Neil

2013-01-01

Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a “brain fitness” game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants’ ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

PubMed

Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

2013-01-01

Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why.

Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

PubMed

Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

2014-01-01

Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load.

Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

PubMed Central

Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

2014-01-01

Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

Cognitive decline and slower reaction time in elderly individuals with mild cognitive impairment.

PubMed

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

Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies

PubMed Central

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

Contribution of cognitive performance and cognitive decline to associations between socioeconomic factors and dementia: A cohort study.

PubMed

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

Social activities are associated with cognitive decline in older Koreans.

PubMed

Kim, DaeHyun; Arai, Hidenori; Kim, SungHi

2017-08-01

Social activity seems to be important for the prevention of cognitive impairment and frailty. The objective of the present study was to investigate whether social activities are associated with the development of cognitive impairment in Korean older people. We analyzed data from the Korean National Longitudinal Study on Aging. A total of 2495 Korean community-dwelling older adults (1163 men and 1332 women) aged between 65 and 79 years at the first wave of the Korean National Longitudinal Study on Aging were used for analysis. Cognitive function was assessed by the Mini-Mental State Examination in 2006 and 2012. Multiple logistic regression analysis was carried out by adjusting covariates, such as age, sex, education, employment, Center for Epidemiological Studies-Depression and instrumental activities of daily living scores, and weight loss. Among the participants, 951 participants (38.1%) showed cognitive decline. Compared with those who participated in a large number of group social activities, multivariate-adjusted odds ratios of cognitive decline in those who participated in a moderate and small number of group activities were 1.18 (95% CI 0.93-1.48) and 1.80 (95% CI 1.16-1.90), respectively. Among six types of group social activities, two types (social club/café and alumni) showed a significant correlation with less cognitive decline; adjusted odds ratios of the group with a small number of activities were 1.31 (95% CI 1.09-1.56) and 1.46 (95% CI 1.10-1.93), respectively, compared with the group with a large number of activities. Personal social activities and the other four types of activities (religious, political, leisure and volunteer) did not affect the outcome. Two social group activities (social club/café and alumni) were significantly associated with less cognitive decline in older Koreans. Geriatr Gerontol Int 2017; 17: 1191-1196. © 2016 Japan Geriatrics Society.

Association between current smoking and cognitive impairment depends on age: A cross-sectional study in Xi'an, China.

PubMed

Liu, Jie; Shang, Suhang; Li, Pei; Deng, Meiying; Chen, Chen; Jiang, Yu; Dang, Liangjun; Qu, Qiumin

2017-09-08

Cigarette smoking is a modifiable risk factor for cognitive impairment, while the relationship between current smoking and cognitive impairment is not fully understood. The objectives were to identify a possible association between current smoking and cognitive impairment depending on age in the Chinese rural population. Data for the study consisted of 1,782 participants (40 years and older) who lived in a rural village in the vicinity of Xi'an, China. Data about smoking history and cognitive function were collected. Cognitive function was scored by the Mini-Mental State Examination. The effect of age on the relationship between current smoking and cognitive impairment was analyzed with interaction and stratified analysis by logistic regression models. Interaction analysis showed that current smoking is positively related with cognitive impairment (odds ratio [OR]=9.067; 95% confidence interval [95% CI] 1.305-62.979; P=.026). However, the interaction term, age by current smoking, is negatively related with cognitive impairment (OR=0.969; 95%CI 0.939-0.999; P=.045). Stratified logistic regression showed that in the 40-65 years of age sublayer, OR of current smoking is 1.966 (P=.044), whereas in the>65 years of age sublayer, the OR is 0.470 (P=.130). This means that the association between current smoking and cognitive impairment with age might be positive (OR>1) in lower age sublayers, but no significant difference in higher age sublayers. In conclusion, current smoking might be positively associated with cognitive impairment in the middle-aged but the relationship declines with increasing age. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

The relative temporal sequence of decline in mobility and cognition among initially unimpaired older adults: Results from the Baltimore Longitudinal Study of Aging.

PubMed

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.

Longitudinal change of biomarkers in cognitive decline.

PubMed

Lo, Raymond Y; Hubbard, Alan E; Shaw, Leslie M; Trojanowski, John Q; Petersen, Ronald C; Aisen, Paul S; Weiner, Michael W; Jagust, William J

2011-10-01

To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Cohort study. The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before

Longitudinal Change of Biomarkers in Cognitive Decline

PubMed Central

Lo, Raymond Y.; Hubbard, Alan E.; Shaw, Leslie M.; Trojanowski, John Q.; Petersen, Ronald C.; Aisen, Paul S.; Weiner, Michael W.; Jagust, William J.

2017-01-01

Objective To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design Cohort study. Setting The 59 study sites for the Alzheimer’s Disease Neuroimaging Initiative. Participants A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease’s Assessment Scale–cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease’s Assessment Scale–cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical

Cognitive Decline Is Associated with Risk Aversion and Temporal Discounting in Older Adults without Dementia

PubMed Central

James, Bryan D.; Boyle, Patricia A.; Yu, Lei; Han, S. Duke; Bennett, David A.

2015-01-01

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that

Cognitive decline is associated with risk aversion and temporal discounting in older adults without dementia.

PubMed

James, Bryan D; Boyle, Patricia A; Yu, Lei; Han, S Duke; Bennett, David A

2015-01-01

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that

Preserved cognitive functions with age are determined by domain-dependent shifts in network responsivity

PubMed Central

Samu, Dávid; Campbell, Karen L.; Tsvetanov, Kamen A.; Shafto, Meredith A.; Brayne, Carol; Bullmore, Edward T.; Calder, Andrew C.; Cusack, Rhodri; Dalgleish, Tim; Duncan, John; Henson, Richard N.; Matthews, Fiona E.; Marslen-Wilson, William D.; Rowe, James B.; Cheung, Teresa; Davis, Simon; Geerligs, Linda; Kievit, Rogier; McCarrey, Anna; Mustafa, Abdur; Price, Darren; Taylor, Jason R.; Treder, Matthias; van Belle, Janna; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Auer, Tibor; Correia, Marta; Gao, Lu; Green, Emma; Henriques, Rafael; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Tyler, Lorraine K.

2017-01-01

Healthy ageing has disparate effects on different cognitive domains. The neural basis of these differences, however, is largely unknown. We investigated this question by using Independent Components Analysis to obtain functional brain components from 98 healthy participants aged 23–87 years from the population-based Cam-CAN cohort. Participants performed two cognitive tasks that show age-related decrease (fluid intelligence and object naming) and a syntactic comprehension task that shows age-related preservation. We report that activation of task-positive neural components predicts inter-individual differences in performance in each task across the adult lifespan. Furthermore, only the two tasks that show performance declines with age show age-related decreases in task-positive activation of neural components and decreasing default mode (DM) suppression. Our results suggest that distributed, multi-component brain responsivity supports cognition across the adult lifespan, and the maintenance of this, along with maintained DM deactivation, characterizes successful ageing and may explain differential ageing trajectories across cognitive domains. PMID:28480894

Preserved cognitive functions with age are determined by domain-dependent shifts in network responsivity.

PubMed

Samu, Dávid; Campbell, Karen L; Tsvetanov, Kamen A; Shafto, Meredith A; Tyler, Lorraine K

2017-05-08

Healthy ageing has disparate effects on different cognitive domains. The neural basis of these differences, however, is largely unknown. We investigated this question by using Independent Components Analysis to obtain functional brain components from 98 healthy participants aged 23-87 years from the population-based Cam-CAN cohort. Participants performed two cognitive tasks that show age-related decrease (fluid intelligence and object naming) and a syntactic comprehension task that shows age-related preservation. We report that activation of task-positive neural components predicts inter-individual differences in performance in each task across the adult lifespan. Furthermore, only the two tasks that show performance declines with age show age-related decreases in task-positive activation of neural components and decreasing default mode (DM) suppression. Our results suggest that distributed, multi-component brain responsivity supports cognition across the adult lifespan, and the maintenance of this, along with maintained DM deactivation, characterizes successful ageing and may explain differential ageing trajectories across cognitive domains.

Higher brain BDNF gene expression is associated with slower cognitive decline in older adults.

PubMed

Buchman, Aron S; Yu, Lei; Boyle, Patricia A; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-02-23

We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression. Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th. Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. © 2016 American Academy of Neurology.

Olfactory discrimination predicts cognitive decline among community-dwelling older adults

PubMed Central

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.

PubMed

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.

Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

PubMed Central

Harrison, Fiona E.; Bowman, Gene L.; Polidori, Maria Cristina

2014-01-01

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. PMID:24763117

Hypertension, cerebrovascular impairment, and cognitive decline in aged AβPP/PS1 mice.

PubMed

Wiesmann, Maximilian; Zerbi, Valerio; Jansen, Diane; Lütjohann, Dieter; Veltien, Andor; Heerschap, Arend; Kiliaan, Amanda J

2017-01-01

Cardiovascular risk factors, especially hypertension, are also major risk factors for Alzheimer's disease (AD). To elucidate the underlying vascular origin of neurodegenerative processes in AD, we investigated the relation between systolic blood pressure (SBP) cerebral blood flow (CBF) and vasoreactivity with brain structure and function in a 16-18 months old double transgenic AβPP swe /PS1 dE9 (AβPP/PS1) mouse model for AD. These aging AβPP/PS1 mice showed an increased SBP linked to a declined regional CBF. Furthermore, using advanced MRI techniques, decline of functional and structural connectivity was revealed in the AD-like mice coupled to impaired cognition, increased locomotor activity, and anxiety-related behavior. Post mortem analyses demonstrated also increased neuroinflammation, and both decreased synaptogenesis and neurogenesis in the AβPP/PS1 mice. Additionally, deviant levels of fatty acids and sterols were present in the brain tissue of the AβPP/PS1 mice indicating maladapted brain fatty acid metabolism. Our findings suggest a link between increased SBP, decreased cerebral hemodynamics and connectivity in an AD mouse model during aging, leading to behavioral and cognitive impairments. As these results mirror the complex clinical symptomatology in the prodromal phase of AD, we suggest that this AD-like murine model could be used to investigate prevention and treatment strategies for early AD patients. Moreover, this study helps to develop more efficient therapies and diagnostics for this very early stage of AD.

Neural Plastic Effects of Cognitive Training on Aging Brain

PubMed Central

Leung, Natalie T. Y.; Tam, Helena M. K.; Chu, Leung W.; Kwok, Timothy C. Y.; Chan, Felix; Lam, Linda C. W.; Woo, Jean; Lee, Tatia M. C.

2015-01-01

Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. PMID:26417460

Mild cognitive decline. A position statement of the Cognitive Decline Group of the European Innovation Partnership for Active and Healthy Ageing (EIPAHA).

PubMed

Apostolo, Joao; Holland, Carol; O'Connell, Matthew D L; Feeney, Joanne; Tabares-Seisdedos, Rafael; Tadros, George; Campos, Elzbieta; Santos, Nadine; Robertson, Deirdre A; Marcucci, Maura; Varela-Nieto, Isabel; Crespo-Facorro, Benedicto; Vieta, Eduard; Navarro-Pardo, Esperanza; Selva-Vera, Gabriel; Balanzá-Martínez, Vicent; Cano, Antonio

2016-01-01

Mild cognitive impairment (MCI) is a term used to describe a level of decline in cognition which is seen as an intermediate stage between normal ageing and dementia, and which many consider to be a prodromal stage of neurodegeneration that may become dementia. That is, it is perceived as a high risk level of cognitive change. The increasing burden of dementia in our society, but also our increasing understanding of its risk factors and potential interventions, require diligent management of MCI in order to find strategies that produce effective prevention of dementia. To update knowledge regarding mild cognitive impairment, and to bring together and appraise evidence about the main features of clinical interest: definitions, prevalence and stability, risk factors, screening, and management and intervention. Literature review and consensus of expert opinion. MCI describes a level of impairment in which deteriorating cognitive functions still allow for reasonable independent living, including some compensatory strategies. While there is evidence for some early risk factors, there is still a need to more precisely delineate and distinguish early manifestations of frank dementia from cognitive impairment that is less likely to progress to dementia, and furthermore to develop improved prospective evidence for positive response to intervention. An important limitation derives from the scarcity of studies that take MCI as an endpoint. Strategies for effective management suffer from the same limitation, since most studies have focused on dementia. Behavioural changes may represent the most cost-effective approach. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Social activity, cognitive decline and dementia risk: a 20-year prospective cohort study.

PubMed

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

Age-related reduction in microcolumnar structure correlates with cognitive decline in ventral but not dorsal area 46 of the rhesus monkey.

PubMed

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.

Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.

PubMed

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.

Widowhood Status as a Risk Factor for Cognitive Decline among Older Adults.

PubMed

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.

Cognitive activities delay onset of memory decline in persons who develop dementia

PubMed Central

Hall, C B.; Lipton, R B.; Sliwinski, M; Katz, M J.; Derby, C A.; Verghese, J

2009-01-01

Background: Persons destined to develop dementia experience an accelerated rate of decline in cognitive ability, particularly in memory. Early life education and participation in cognitively stimulating leisure activities later in life are 2 factors thought to reflect cognitive reserve, which may delay the onset of the memory decline in the preclinical stages of dementia. Methods: We followed 488 initially cognitively intact community residing individuals with epidemiologic, clinical, and cognitive assessments every 12 to 18 months in the Bronx Aging Study. We assessed the influence of self-reported participation in cognitively stimulating leisure activities on the onset of accelerated memory decline as measured by the Buschke Selective Reminding Test in 101 individuals who developed incident dementia using a change point model. Results: Each additional self-reported day of cognitive activity at baseline delayed the onset of accelerated memory decline by 0.18 years. Higher baseline levels of cognitive activity were associated with more rapid memory decline after that onset. Inclusion of education did not significantly add to the fit of the model beyond the effect of cognitive activities. Conclusions: Our findings show that late life cognitive activities influence cognitive reserve independently of education. The effect of early life education on cognitive reserve may be mediated by cognitive activity later in life. Alternatively, early life education may be a determinant of cognitive reserve, and individuals with more education may choose to participate in cognitive activities without influencing reserve. Future studies should examine the efficacy of increasing participation in cognitive activities to prevent or delay dementia. GLOSSARY AD = Alzheimer disease; BL = baseline; CAS = Cognitive Activity Scale; CI = confidence interval; DSM = Diagnostic and Statistical Manual of Mental Disorders; dx = diagnosis; NIA = National Institute on Aging; SRT = Selective

Brain Network Changes and Memory Decline in Aging

PubMed Central

Beason-Held, Lori L.; Hohman, Timothy J.; Venkatraman, Vijay; An, Yang; Resnick, Susan M.

2016-01-01

One theory of age-related cognitive decline proposes that changes within the default mode network (DMN) of the brain impact the ability to successfully perform cognitive operations. To investigate this theory, we examined functional covariance within brain networks using regional cerebral blood flow data, measured by 15O-water PET, from 99 participants (mean baseline age 68.6 ±7.5) in the Baltimore Longitudinal Study of Aging collected over a 7.4 year period. The sample was divided in tertiles based on longitudinal performance on a verbal recognition memory task administered during scanning, and functional covariance was compared between the upper (improvers) and lower (decliners) tertile groups. The DMN and verbal memory networks (VMN) were then examined during the verbal memory scan condition. For each network, group differences in node-to-network coherence and individual node-to-node covariance relationships were assessed at baseline and in change over time. Compared with improvers, decliners showed differences in node-to-network coherence and in node-to-node relationships in the DMN but not the VMN during verbal memory. These DMN differences reflected greater covariance with better task performance at baseline and both increasing and declining covariance with declining task performance over time for decliners. When examined during the resting state alone, the direction of change in DMN covariance was similar to that seen during task performance, but node-to-node relationships differed from those observed during the task condition. These results suggest that disengagement of DMN components during task performance is not essential for successful cognitive performance as previously proposed. Instead, a proper balance in network processes may be needed to support optimal task performance. PMID:27319002

Self-Reported History of Chemotherapy and Cognitive Decline in Adults Aged 60 and Older: The PATH Through Life Project.

PubMed

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.

Carotid disease at age 73 and cognitive change from age 70 to 76 years: A longitudinal cohort study

PubMed Central

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.

PubMed

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.

Changes in physical activity and cognitive decline in older adults living in the community.

PubMed

Lee, Yunhwan; Kim, Jinhee; Han, Eun Sook; Chae, Songi; Ryu, Mikyung; Ahn, Kwang Ho; Park, Eun Ju

2015-01-01

Accumulating evidence suggests that physical activity may be beneficial in preserving cognition in late life. This study examined the association between baseline and changes in physical activity and cognitive decline in community-dwelling older people. Data were from the Korean Longitudinal Study of Aging, with 2605 aged 65 years and older subjects interviewed in 2006 and followed up for 2 years. Cognitive decline was defined by calculating the Reliable Change Index using the Mini-Mental State Examination. Physical activity levels were categorized as sedentary, low, or high. Changes in physical activity were classified as inactive, decreaser, increaser, or active. Logistic regression analysis of baseline and changes in physical activity with cognitive decline was performed. Compared with the sedentary group at baseline, both the low and high activity groups were less likely to experience cognitive decline. The active (odds ratio [OR] = 0.40, 95 % confidence interval [CI] 0.23-0.68) and increaser (OR = 0.45, 95 % CI 0.27-0.74) group, compared with the inactive counterpart, demonstrated a significantly lower likelihood of cognitive decline. Older adults who remained active or increased activity over time had a reduced risk of cognitive decline. Engagement in physical activity in late life may have cognitive health benefits.

Ginkgo biloba for Preventing Cognitive Decline in Older Adults

PubMed Central

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

Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive Function in People With HIV.

PubMed

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.

Cognitive Decline and Older Driver Crash Risk.

PubMed

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.

Cognitive decline in Parkinson disease

PubMed Central

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

Effect of Aging on ERP Components of Cognitive Control

PubMed Central

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

The emerging role of dietary fructose in obesity and cognitive decline.

PubMed

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.

Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging.

PubMed

Papenberg, Goran; Ferencz, Beata; Mangialasche, Francesca; Mecocci, Patrizia; Cecchetti, Roberta; Kalpouzos, Grégoria; Fratiglioni, Laura; Bäckman, Lars

2016-10-01

Physical activity has been positively associated with gray-matter integrity. In contrast, pro-inflammatory cytokines seem to have negative effects on the aging brain and have been related to dementia. It was investigated whether an inactive lifestyle and high levels of inflammation resulted in smaller gray-matter volumes and predicted cognitive decline across 6 years in a population-based study of older adults (n = 414). Self-reported physical activity (fitness-enhancing, health-enhancing, inadequate) was linked to gray-matter volume, such that individuals with inadequate physical activity had the least gray matter. There were no overall associations between different pro-and anti-inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, IL-12p70, G-CSF, and TNF-α) and gray-matter integrity. However, persons with inadequate activity and high levels of the pro-inflammatory marker IL-12p40 had smaller volumes of lateral prefrontal cortex and hippocampus and declined more on the Mini-Mental State Examination test over 6 years compared with physically inactive individuals with low levels of IL-12p40 and to more physically active persons, irrespective of their levels of IL-12p40. These patterns of data suggested that inflammation was particularly detrimental in inactive older adults and may exacerbate the negative effects of physical inactivity on brain and cognition in old age. Hum Brain Mapp 37:3462-3473, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease: A Retrospective Cohort Study.

PubMed

Aguirre-Acevedo, Daniel C; Lopera, Francisco; Henao, Eliana; Tirado, Victoria; Muñoz, Claudia; Giraldo, Margarita; Bangdiwala, Shrikant I; Reiman, Eric M; Tariot, Pierre N; Langbaum, Jessica B; Quiroz, Yakeel T; Jaimes, Fabian

2016-04-01

Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline. A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word

The Dynamic Relationship Between Physical Function and Cognition in Longitudinal Aging Cohorts

PubMed Central

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

Age-dependent decline of nogo-a protein in the mouse cerebrum.

PubMed

Kumari, Anita; Thakur, M K

2014-11-01

Nogo-A, a myelin-associated neurite growth inhibitory protein, is implicated in synaptic plasticity. It binds to its receptor namely the Nogo-66 receptor1 (NgR1) and regulates filamentous (F) actin dynamics via small GTPases of the Rho family, RhoA kinase (ROCK), LimK and cofilin. These proteins are associated with the structural plasticity, one of the components of synaptic plasticity, which is known to decline with normal aging. So, the level of Nogo-A and its receptor NgR1 are likely to vary during normal brain aging. However, it is not clearly understood how the levels of Nogo-A and its receptor NgR1 change in the cerebrum during aging. Several studies show an age- and gender-dependent decline in synaptic plasticity. Therefore, the present study was planned to analyze the relative changes in the mRNA and protein levels of Nogo-A and NgR1 in both male and female mice cerebrum during normal aging. Western blot analysis has shown decrease in Nogo-A protein level during aging in both male and female mice cerebrum. This was further confirmed by immunofluorescence analysis. RT-PCR analysis of Nogo-A mRNA showed no significant difference in the above-mentioned groups. This was also supported by in situ hybridization. NgR1 protein and its mRNA expression levels showed no significant alteration with aging in the cerebrum of both male and female mice. Taken together, we speculate that the downregulation of Nogo-A protein might have a role in the altered synaptic plasticity during aging.

Education and trajectories of cognitive decline over 9 years in very old people: methods and risk analysis.

PubMed

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.

Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve.

PubMed

Mungas, Dan; Gavett, Brandon; Fletcher, Evan; Farias, Sarah Tomaszewski; DeCarli, Charles; Reed, Bruce

2018-08-01

Level of education is often regarded as a proxy for cognitive reserve in older adults. This implies that brain degeneration has a smaller effect on cognitive decline in those with more education, but this has not been directly tested in previous research. We examined how education, quantitative magnetic resonance imaging-based measurement of brain degeneration, and their interaction affect cognitive decline in diverse older adults spanning the spectrum from normal cognition to dementia. Gray matter atrophy was strongly related to cognitive decline. While education was not related to cognitive decline, brain atrophy had a stronger effect on cognitive decline in those with more education. Importantly, high education was associated with slower decline in individuals with lesser atrophy but with faster decline in those with greater atrophy. This moderation effect was observed in Hispanics (who had high heterogeneity of education) but not in African-Americans or Caucasians. These results suggest that education is an indicator of cognitive reserve in individuals with low levels of brain degeneration, but the protective effect of higher education is rapidly depleted as brain degeneration progresses. Copyright © 2018 Elsevier Inc. All rights reserved.

The emerging role of dietary fructose in obesity and cognitive decline

PubMed Central

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

Cognitive decline and dementia in the oldest-old.

PubMed

Kravitz, Efrat; Schmeidler, James; Beeri, Michal Schnaider

2012-10-01

The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer's disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.

Cognitive Decline and Dementia in the Oldest-Old

PubMed Central

Kravitz, Efrat; Schmeidler, James; Beeri, Michal Schnaider

2012-01-01

The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer’s disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out everyday activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology is accumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life. PMID:23908850

Kidney function and cognitive decline in an oldest-old Chinese population.

PubMed

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.

Differences in quantitative methods for measuring subjective cognitive decline - results from a prospective memory clinic study.

PubMed

Vogel, Asmus; Salem, Lise Cronberg; Andersen, Birgitte Bo; Waldemar, Gunhild

2016-09-01

Cognitive complaints occur frequently in elderly people and may be a risk factor for dementia and cognitive decline. Results from studies on subjective cognitive decline are difficult to compare due to variability in assessment methods, and little is known about how different methods influence reports of cognitive decline. The Subjective Memory Complaints Scale (SMC) and The Memory Complaint Questionnaire (MAC-Q) were applied in 121 mixed memory clinic patients with mild cognitive symptoms (mean MMSE = 26.8, SD 2.7). The scales were applied independently and raters were blinded to results from the other scale. Scales were not used for diagnostic classification. Cognitive performances and depressive symptoms were also rated. We studied the association between the two measures and investigated the scales' relation to depressive symptoms, age, and cognitive status. SMC and MAC-Q were significantly associated (r = 0.44, N = 121, p = 0.015) and both scales had a wide range of scores. In this mixed cohort of patients, younger age was associated with higher SMC scores. There were no significant correlations between cognitive test performances and scales measuring subjective decline. Depression scores were significantly correlated to both scales measuring subjective decline. Linear regression models showed that age did not have a significant contribution to the variance in subjective memory beyond that of depressive symptoms. Measures for subjective cognitive decline are not interchangeable when used in memory clinics and the application of different scales in previous studies is an important factor as to why studies show variability in the association between subjective cognitive decline and background data and/or clinical results. Careful consideration should be taken as to which questions are relevant and have validity when operationalizing subjective cognitive decline.

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921.

PubMed

Schiepers, O J G; Harris, S E; Gow, A J; Pattie, A; Brett, C E; Starr, J M; Deary, I J

2012-03-01

Carriers of the APOE E4 allele have an increased risk of developing Alzheimer's disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n=501), and again at mean ages of 83 (n=284) and 87 (n=187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In non-demented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimer's disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.

Association of Source of Memory Complaints and Increased Risk of Cognitive Impairment and Cognitive Decline: A Community-Based Study.

PubMed

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.

Metabolic Syndrome and 16-year Cognitive Decline in Community-Dwelling Older Adults

PubMed Central

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

Trajectories of social withdrawal and cognitive decline in the schizophrenia prodrome.

PubMed

Cullen, Kathryn; Guimaraes, Angela; Wozniak, Jeffrey; Anjum, Afshan; Schulz, S Charles; White, Tonya

2011-01-01

Schizophrenia is a heterogeneous neurodevelopmental disorder. Patients with high levels of negative symptoms have been identified as a specific subtype, but little is known about how the neurodevelopmental course may differ in this group. This study aimed to characterize developmental trajectories of premorbid social withdrawal and cognitive decline between patients with high versus low levels of negative symptoms in youth with schizophrenia-spectrum disorders. A standardized timeline was used to delineate the emergence of psychosis, social withdrawal, and cognitive decline in 52 subjects aged 8 to 19 with schizophrenia (n=36), schizophreniform (n=6), or schizoaffective disorder (n=10). The sample was divided into subgroups of high- (n=26) versus low- (n=26) negative symptoms, and developmental trajectories of premorbid symptoms were compared between groups. Mean ages for emergence of social withdrawal, cognitive decline, and psychosis were 11.1 years (SD=2.5), 11.9 (SD=4.4) and 13.2 years (SD=1.2), respectively. In the high-negative symptom group, the premorbid developmental trajectory for social withdrawal was more protracted. This group also had more severe cognitive decline at the onset of psychosis, but the premorbid trajectories for cognitive decline did not differ significantly between groups. This work documents a more severe and protracted trajectory of premorbid social withdrawal in patients with high levels of negative symptoms in comparison to those with low-negative symptoms. The findings reported here are supportive of the hypothesis that patients with illness characterized by high levels of negative symptoms may represent a subgroup with distinct neurodevelopmental abnormalities.

Rates of decline in Alzheimer disease decrease with age.

PubMed

Holland, Dominic; Desikan, Rahul S; Dale, Anders M; McEvoy, Linda K

2012-01-01

Age is the strongest risk factor for sporadic Alzheimer disease (AD), yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI), and cognitively healthy (HC) individuals aged 65 to 90 years (total n = 723). The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Aβ(1-42), tau, and phospho-tau(181p) (ptau), showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old. Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.

Visual and hearing impairments are associated with cognitive decline in older people.

PubMed

Maharani, Asri; Dawes, Piers; Nazroo, James; Tampubolon, Gindo; Pendleton, Neil

2018-04-25

highly prevalagent hearing and vision sensory impairments among older people may contribute to the risk of cognitive decline and pathological impairments including dementia. This study aims to determine whether single and dual sensory impairment (hearing and/or vision) are independently associated with cognitive decline among older adults and to describe cognitive trajectories according to their impairment pattern. we used data from totals of 13,123, 11,417 and 21,265 respondents aged 50+ at baseline from the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE), respectively. We performed growth curve analysis to identify cognitive trajectories, and a joint model was used to deal with attrition problems in longitudinal ageing surveys. respondents with a single sensory impairment had lower episodic memory score than those without sensory impairment in HRS (β = -0.15, P < 0.001), ELSA (β= -0.14, P< 0.001) and SHARE (β= -0.26, P < 0.001). The analysis further shows that older adults with dual sensory impairment in HRS (β= -0.25, P < 0.001), ELSA (β= -0.35, P< 0.001) and SHARE (β= -0.68, P < 0.001) remembered fewer words compared with those with no sensory impairment. The stronger associations between sensory impairment and lower episodic memory levels were found in the joint model which accounted for attrition. hearing and/or vision impairments are a marker for the risk of cognitive decline that could inform preventative interventions to maximise cognitive health and longevity. Further studies are needed to investigate how sensory markers could inform strategies to improve cognitive ageing.

Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study.

PubMed

Rabin, Jennifer S; Schultz, Aaron P; Hedden, Trey; Viswanathan, Anand; Marshall, Gad A; Kilpatrick, Emily; Klein, Hannah; Buckley, Rachel F; Yang, Hyun-Sik; Properzi, Michael; Rao, Vaishnavi; Kirn, Dylan R; Papp, Kathryn V; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Chhatwal, Jasmeer P

2018-05-21

Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease is crucial for successful prevention of dementia. Vascular risk and β-amyloid (Aβ) pathology commonly co-occur in older adults and are significant causes of cognitive impairment. To determine whether vascular risk and Aβ burden act additively or synergistically to promote cognitive decline in clinically normal older adults; and, secondarily, to evaluate the unique influence of vascular risk on prospective cognitive decline beyond that of commonly used imaging biomarkers, including Aβ burden, hippocampal volume, fludeoxyglucose F18-labeled (FDG) positron emission tomography (PET), and white matter hyperintensities, a marker of cerebrovascular disease. In this longitudinal observational study, we examined clinically normal older adults from the Harvard Aging Brain Study. Participants were required to have baseline imaging data (FDG-PET, Aβ-PET, and magnetic resonance imaging), baseline medical data to quantify vascular risk, and at least 1 follow-up neuropsychological visit. Data collection began in 2010 and is ongoing. Data analysis was performed on data collected between 2010 and 2017. Vascular risk was quantified using the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score. We measured Aβ burden with Pittsburgh Compound-B PET. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite. Models were corrected for baseline age, sex, years of education, and apolipoprotein E ε4 status. Of the 223 participants, 130 (58.3%) were women. The mean (SD) age was 73.7 (6.0) years, and the mean (SD) follow-up time was 3.7 (1.2) years. Faster cognitive decline was associated with both a higher FHS-CVD risk score (β = -0.064; 95% CI, -0.094 to -0.033; P < .001) and higher Aβ burden (β = -0.058; 95% CI, -0.079 to -0.037; P < .001). The interaction of the FHS-CVD risk score and Aβ burden with time

Medical Complications Predict Cognitive Decline in Nondemented Hip Fracture Patients-Results of a Prospective Observational Study.

PubMed

Hack, Juliana; Eschbach, Daphne; Aigner, Rene; Oberkircher, Ludwig; Ruchholtz, Steffen; Bliemel, Christopher; Buecking, Benjamin

2018-03-01

The aim of this study was to identify factors that are associated with cognitive decline in the long-term follow-up after hip fractures in previously nondemented patients. A consecutive series of 402 patients with hip fractures admitted to our university hospital were analyzed. After exclusion of all patients with preexisting dementia, 266 patients were included, of which 188 could be examined 6 months after surgery. Additional to several demographic data, cognitive ability was assessed using the Mini-Mental State Examination (MMSE). Patients with 19 or less points on the MMSE were considered demented. Furthermore, geriatric scores were recorded, as well as perioperative medical complications. Mini-Mental State Examination was performed again 6 months after surgery. Of 188 previously nondemented patients, 12 (6.4%) patients showed a cognitive decline during the 6 months of follow-up. Multivariate regression analysis showed that age ( P = .040) and medical complications ( P = .048) were the only significant independent influencing factors for cognitive decline. In our patient population, the incidence of dementia exceeded the average age-appropriate cognitive decline. Significant independent influencing factors for cognitive decline were age and medical complications.

Functional brain imaging of episodic memory decline in ageing.

PubMed

Nyberg, L

2017-01-01

The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Lower cognitive reserve in the aging human immunodeficiency virus-infected brain.

PubMed

Chang, Linda; Holt, John L; Yakupov, Renat; Jiang, Caroline S; Ernst, Thomas

2013-04-01

More HIV-infected individuals are living longer; however, how their brain function is affected by aging is not well understood. One hundred twenty-two men (56 seronegative control [SN] subjects, 37 HIV subjects with normal cognition [HIV+NC], 29 with HIV-associated neurocognitive disorder [HAND]) performed neuropsychological tests and had acceptable functional magnetic resonance imaging scans at 3 Tesla during tasks with increasing attentional load. With older age, SN and HIV+NC subjects showed increased activation in the left posterior (reserve, "bottom-up") attention network for low attentional-load tasks, and further increased activation in the left posterior and anterior ("top-down") attention network on intermediate (HIV+NC only) and high attentional-load tasks. HAND subjects had only age-dependent decreases in activation. Age-dependent changes in brain activation differed between the 3 groups, primarily in the left frontal regions (despite similar brain atrophy). HIV and aging act synergistically or interactively to exacerbate brain activation abnormalities in different brain regions, suggestive of a neuroadaptive mechanism in the attention network to compensate for declined neural efficiency. While the SN and HIV+NC subjects compensated for their declining attention with age by using reserve and "top-down" attentional networks, older HAND subjects were unable to compensate which resulted in cognitive decline. Copyright © 2013 Elsevier Inc. All rights reserved.

Cognitive performance and age-related changes in the hippocampal proteome.

PubMed

Freeman, W M; VanGuilder, H D; Bennett, C; Sonntag, W E

2009-03-03

Declining cognitive performance is associated with increasing age, even in the absence of overt pathological processes. We and others have reported that declining cognitive performance is associated with age-related changes in brain glucose utilization, long-term potentiation and paired-pulse facilitation, protein expression, neurotransmitter levels, and trophic factors. However, it is unclear whether these changes are causes or symptoms of the underlying alterations in dendritic and synaptic morphology that occur with age. In this study, we examined the hippocampal proteome for age- and cognition-associated changes in behaviorally stratified young and old rats, using two-dimensional in-gel electrophoresis and MS/MS. Comparison of old cognitively intact with old cognitively impaired animals revealed additional changes that would not have been detected otherwise. Interestingly, not all age-related changes in protein expression were associated with cognitive decline, and distinct differences in protein expression were found when comparing old cognitively intact with old cognitively impaired rats. A large number of protein changes with age were related to the glycolysis/gluconeogenesis pathway. In total, the proteomic changes suggest that age-related alterations act synergistically with other perturbations to result in cognitive decline. This study also demonstrates the importance of examining behaviorally-defined animals in proteomic studies, as comparison of young to old animals regardless of behavioral performance would have failed to detect many cognitive impairment-specific protein expression changes evident when behavioral stratification data were used.

Experimental evolution of slowed cognitive aging in Drosophila melanogaster.

PubMed

Zwoinska, Martyna K; Maklakov, Alexei A; Kawecki, Tadeusz J; Hollis, Brian

2017-03-01

Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories. © 2016 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

White matter tract covariance patterns predict age-declining cognitive abilities.

PubMed

Gazes, Yunglin; Bowman, F DuBois; Razlighi, Qolamreza R; O'Shea, Deirdre; Stern, Yaakov; Habeck, Christian

2016-01-15

Previous studies investigating the relationship of white matter (WM) integrity to cognitive abilities and aging have either focused on a global measure or a few selected WM tracts. Ideally, contribution from all of the WM tracts should be evaluated at the same time. However, the high collinearity among WM tracts precludes systematic examination of WM tracts simultaneously without sacrificing statistical power due to stringent multiple-comparison corrections. Multivariate covariance techniques enable comprehensive simultaneous examination of all WM tracts without being penalized for high collinearity among observations. In this study, Scaled Subprofile Modeling (SSM) was applied to the mean integrity of 18 major WM tracts to extract covariance patterns that optimally predicted four cognitive abilities (perceptual speed, episodic memory, fluid reasoning, and vocabulary) in 346 participants across ages 20 to 79years old. Using expression of the covariance patterns, age-independent effects of white matter integrity on cognition and the indirect effect of WM integrity on age-related differences in cognition were tested separately, but inferences from the indirect analyses were cautiously made given that cross-sectional data set was used in the analysis. A separate covariance pattern was identified that significantly predicted each cognitive ability after controlling for age except for vocabulary, but the age by WM covariance pattern interaction was not significant for any of the three abilities. Furthermore, each of the patterns mediated the effect of age on the respective cognitive ability. A distinct set of WM tracts was most influential in each of the three patterns. The WM covariance pattern accounting for fluid reasoning showed the most number of influential WM tracts whereas the episodic memory pattern showed the least number. Specific patterns of WM tracts make significant contributions to the age-related differences in perceptual speed, episodic memory, and

Ten-year change in plasma amyloid beta levels and late-life cognitive decline.

PubMed

Okereke, Olivia I; Xia, Weiming; Selkoe, Dennis J; Grodstein, Francine

2009-10-01

Plasma levels of amyloid beta peptide (Abeta) are potential biomarkers of early cognitive impairment and decline and of Alzheimer disease risk. To relate midlife plasma Abeta measures and 10-year change in plasma Abeta measures since midlife to late-life cognitive decline. Prospective study of a population-based sample. Academic research. Plasma Abeta40 and Abeta42 levels were measured in 481 Nurses' Health Study participants in late midlife (mean age, 63.6 years) and again 10 years later (mean age, 74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed 3 repeated telephone-based assessments (mean span, 4.1 years). Multivariable linear mixed-effects models were used to estimate relations of midlife plasma Abeta40 to Abeta42 ratios and Abeta42 levels to late-life cognitive decline, as well as relations of 10-year change in Abeta40 to Abeta42 ratios and Abeta42 levels to cognitive decline. The 3 primary outcomes were the Telephone Interview for Cognitive Status (TICS) findings, a global score averaging the results of all tests (TICS, immediate and delayed verbal recall, category fluency, and attention), and a verbal memory score averaging the results of 4 tests of verbal recall. Higher midlife plasma Abeta40 to Abeta42 ratios were associated with worse late-life decline on the global score (P = .04 for trend). Furthermore, increase in Abeta40 to Abeta42 ratios since midlife predicted greater decline in the global score (P = .03 for trend) and in the TICS (P = .02 for trend). There was no association of cognitive decline with midlife plasma Abeta42 levels alone or with change in Abeta42 levels since midlife. In this large community-dwelling sample, higher plasma Abeta40 to Abeta42 ratios in late midlife and increases in Abeta40 to Abeta42 ratios 10 years later were significantly associated with greater decline in global cognition at late life.

Age-Dependent Pleiotropy Between General Cognitive Function and Major Psychiatric Disorders.

PubMed

Hill, W David; Davies, Gail; Liewald, David C; McIntosh, Andrew M; Deary, Ian J

2016-08-15

General cognitive function predicts psychiatric illness across the life course. This study examines the role of pleiotropy in explaining the link between cognitive function and psychiatric disorder. We used two large genome-wide association study data sets on cognitive function-one from older age, n = 53,949, and one from childhood, n = 12,441. We also used genome-wide association study data on educational attainment, n = 95,427, to examine the validity of its use as a proxy phenotype for cognitive function. Using a new method, linkage disequilibrium regression, we derived genetic correlations, free from the confounding of clinical state between psychiatric illness and cognitive function. We found a genetic correlation of .711 (p = 2.26e-12) across the life course for general cognitive function. We also showed a positive genetic correlation between autism spectrum disorder and cognitive function in childhood (rg = .360, p = .0009) and for educational attainment (rg = .322, p = 1.37e-5) but not in older age. In schizophrenia, we found a negative genetic correlation between older age cognitive function (rg = -.231, p = 3.81e-12) but not in childhood or for educational attainment. For Alzheimer's disease, we found negative genetic correlations with childhood cognitive function (rg = -.341, p = .001), educational attainment (rg = -.324, p = 1.15e-5), and with older age cognitive function (rg = -.324, p = 1.78e-5). The pleiotropy exhibited between cognitive function and psychiatric disorders changed across the life course. These age-dependent associations might explain why negative selection has not removed variants causally associated with autism spectrum disorder or schizophrenia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Lipid Profiles and APOE4 Allele Impact Midlife Cognitive Decline in HIV-Infected Men on Antiretroviral Therapy.

PubMed

Mukerji, Shibani S; Locascio, Joseph J; Misra, Vikas; Lorenz, David R; Holman, Alex; Dutta, Anupriya; Penugonda, Sudhir; Wolinsky, Steven M; Gabuzda, Dana

2016-10-15

Dyslipidemia and apolipoprotein E4 (APOE ϵ4) allele are risk factors for age-related cognitive decline, but how these risks are modified by human immunodeficiency virus (HIV) infection is unclear. In a longitudinal nested study from the Multicenter AIDS Cohort Study, 273 HIV type 1-infected (HIV(+)) men aged 50-65 years with baseline HIV RNA <400 copies/mL and on continuous antiretroviral therapy (ART) in ≥95% of follow-up visits were matched by sociodemographic variables to 516 HIV-uninfected (HIV(-)) controls. The association between lipid markers (total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides), APOE genotype, and cognitive decline in HIV infection was examined using mixed-effects models. The median baseline age of participants was 51, 81% were white, and 89% had education >12 years. HIV(+) men had similar baseline total cholesterol and LDL-C, but lower HDL-C and higher triglycerides than controls (P < .001). Higher total cholesterol and LDL-C were associated with faster rates of cognitive decline (P < .01), whereas higher HDL-C attenuated decline (P = .02) in HIV(+) men. In HIV(+) men with elevated cholesterol, statin use was associated with a slower estimated rate of decline (P = .02). APOE ϵ4 genotype accelerated cognitive decline in HIV(+) but not HIV(-) men (P = .01), with trajectories diverging from HIV(-) ε4 carriers after age 50. Total cholesterol levels did not modify the association of ϵ4 genotype with decline (P = .9). Elevated cholesterol and APOE ϵ4 genotype are independent risk factors for cognitive decline in ART-adherent HIV(+) men aged >50 years. Treatment of dyslipidemia may be an effective strategy to reduce cognitive decline in older HIV(+) individuals. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Ability of university-level education to prevent age-related decline in emotional intelligence

PubMed Central

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

Microsurgeons do better--tactile training might prevent the age-dependent decline of the sensibility of the hand.

PubMed

Schmauss, Daniel; Megerle, Kai; Weinzierl, Andrea; Agua, Kariem; Cerny, Michael; Schmauss, Verena; Lohmeyer, Joern A; Machens, Hans-Guenther; Erne, Holger

2015-12-01

Recent data demonstrate that the normal sensibility of the hand seems to be age-dependent with the best values in the third decade and a consecutive deterioration afterwards. However, it is not clear if long-term tactile training might prevent this age-dependent decline. We evaluated sensibility of the hand in 125 surgeons aged between 26 and 75 years who perform microsurgical operations, thereby undergoing regular tactile training. We examined sensibility of the radial digital nerve of the index finger (N3) and the ulnar digital nerve of the small finger (N10) using static and moving two-point discrimination (2PD) tests and compared the results to 154 age-matched individuals without specific long-term tactile training. We found significantly lower static and moving 2PD values for the sixth, seventh, and eighth decade of life in the microsurgery group compared to the control group (p < 0.05). This study demonstrates that long-term tactile training might prevent the known age-dependent decline of the sensibility of the hand. © 2015 Peripheral Nerve Society.

Functional MRI evidence for the decline of word retrieval and generation during normal aging.

PubMed

Baciu, M; Boudiaf, N; Cousin, E; Perrone-Bertolotti, M; Pichat, C; Fournet, N; Chainay, H; Lamalle, L; Krainik, A

2016-02-01

This fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing, due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming, and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automatisms and overlearned information. In terms of behavioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuropsychological scores, and the overactivation of these uncorrelated

Adverse Childhood and Recent Negative Life Events: Contrasting Associations With Cognitive Decline in Older Persons.

PubMed

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.

Microbleeds do not affect rate of cognitive decline in Alzheimer disease.

PubMed

van der Vlies, Annelies E; Goos, Jeroen D C; Barkhof, Frederik; Scheltens, Philip; van der Flier, Wiesje M

2012-08-21

To investigate the relationship between brain microbleeds (MBs) and the rate of cognitive decline in Alzheimer disease (AD). In this cohort study, we studied 221 patients with AD with available baseline MRI scans (1.0 or 1.5 T) and at least 2 Mini-Mental State Examinations (MMSE) scores obtained more than 1 year apart from our memory clinic. Mean ± SD follow-up time was 3 ± 1 years, and patients had a median of 4 MMSE scores (range 2-17). We used linear mixed models with sex and age as covariates to investigate whether MBs influenced the rate of cognitive decline. Mean age was 68 ± 9 years, 109 (49%) patients were female, and the baseline MMSE score was 22 ± 4. There were 39 patients (18%) with MBs (median 2, range 1-27) and 182 without. Linear mixed models showed that overall patients declined 2 MMSE points per year. We found no association of the presence of MBs with baseline MMSE or change in MMSE. Adjustment for atrophy, white matter hyperintensities, lacunes, and vascular risk factors did not change the results nor did stratification for MB location, APOE ε4 carriership, or age at onset (≤65 years vs >65 years). Repeating the analyses with number of MBs as predictor rendered similar results. MBs did not influence the rate of cognitive decline in patients with AD. The formerly reported increased risk of mortality in patients with MBs seems not to be attributable to a steeper rate of decline per se but might be due to vascular events, including (hemorrhagic) stroke.

Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease.

PubMed

Cho, Jinkyung; Shin, Min-Kyoo; Kim, Donghyun; Lee, Inhwan; Kim, Shinuk; Kang, Hyunsik

2015-09-01

This study investigated the effect of treadmill running on cognitive declines in the early and advanced stages of Alzheimer disease (AD) in 3xTg-AD mice. At 4 months of age, 3xTg-AD mice (N = 24) were assigned to control (AD + CON, n = 12) or exercise (AD + EX, n = 12) group. At 24 months of age, 3xTg-AD mice (N = 16) were assigned to AD + CON (n = 8) or AD + EX (n = 8) group. The AD + EX mice were subjected to treadmill running for 12 wk. At each pathological stage, the background strain mice were included as wild-type control (WT + CON, n = 8-12). At the early stage of AD, 3xTg-AD mice had impaired short- and long-term memory based on Morris water maze along with higher cortical Aβ deposition, higher hippocampal and cortical tau pathology, and lower hippocampal and cortical PSD-95 and synaptophysin. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the tau pathology along with suppression of the decreased PSD-95 and synaptophysin in the hippocampus and cortex. At the advanced stage of AD, 3xTg-AD mice had impaired short- and long-term memory along with higher levels of Aβ deposition, soluble Aβ1-40 and Aβ1-42, tau pathology, and lower levels of brain-derived neurotrophic factor, PSD-95, and synaptophysin in the hippocampus and cortex. A 12-wk treadmill running reversed the impaired cognitive declines and significantly improved the Aβ and tau pathology along with suppression of the decreased synaptic proteins and brain-derived neurotrophic factor in the hippocampus and cortex. The current findings suggest that treadmill running provides a nonpharmacological means to combat cognitive declines due to AD pathology.

Education and the cognitive decline associated with MRI-defined brain infarct.

PubMed

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.

Falls and cognitive decline in Mexican Americans 75 years and older

PubMed Central

Padubidri, Anokha; Al Snih, Soham; Samper-Ternent, Rafael; Markides, Kyriakos S; Ottenbacher, Kenneth J; Raji, Mukaila A

2014-01-01

Background Little is known about long-term emotional and cognitive consequences of falls. We examined the association between falls and subsequent cognitive decline, and tested the hypothesis that depression would mediate any falls–cognition association among cognitively intact Hispanic Elders. Methods We used data from the Hispanic Established Population for the Epidemiological Study of the Elderly to examine change in Mini Mental State Examination (MMSE) scores over the 6-year period according to number of falls. All participants (N=1,119) had MMSE scores ≥21 and complete data on Center for Epidemiologic Studies of Depression Scale, social and demographic factors, medical conditions (diabetes, heart attack, stroke, and hypertension), and hand grip muscle strength. Results At baseline, participants’ mean age was 80.8 years (range, 74–109), mean education was 6.3 years (range, 0–17), and mean MMSE was 25.2 (range, 21–30). Of the 1,119 participants, 15.8% experienced one fall and 14.4% had two or more falls. In mixed model analyses, having two or more falls was associated with greater decline in MMSE score (estimate =−0.81, standard error =0.19, P<0.0001) compared to having no fall, after adjusting for age, sex, marital status, and education. The magnitude of the association decreased (estimate =−0.65, standard error =0.19, P=0.0007) when adjustment was made for high depressive symptoms, suggesting a possible mediating effect of depression on the falls–cognition association. Female sex, high level of education, and high performance in hand grip muscle strength were associated with a slower decline in MMSE scores. Conclusion Having two or more falls was independently associated with steeper decline in cognition over 6 years, with a possible mediating effect of depression on the falls–cognition association. PMID:24790424

Healthy eating and reduced risk of cognitive decline

PubMed Central

Dehghan, Mahshid; O'Donnell, Martin; Anderson, Craig; Teo, Koon; Gao, Peggy; Sleight, Peter; Dagenais, Gilles; Probstfield, Jeffrey L.; Mente, Andrew; Yusuf, Salim

2015-01-01

Objective: We sought to determine the association of dietary factors and risk of cognitive decline in a population at high risk of cardiovascular disease. Methods: Baseline dietary intake and measures of the Mini-Mental State Examination were recorded in 27,860 men and women who were enrolled in 2 international parallel trials of the ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) studies. We measured diet quality using the modified Alternative Healthy Eating Index. Cox proportional hazards regression was used to determine the association between diet quality and risk of ≥3-point decline in Mini-Mental State Examination score, and reported as hazard ratio with 95% confidence intervals with adjustment for covariates. Results: During 56 months of follow-up, 4,699 cases of cognitive decline occurred. We observed lower risk of cognitive decline among those in the healthiest dietary quintile of modified Alternative Healthy Eating Index compared with lowest quintile (hazard ratio 0.76, 95% confidence interval 0.66–0.86, Q5 vs Q1). Lower risk of cognitive decline was consistent regardless of baseline cognitive level. Conclusion: We found that higher diet quality was associated with a reduced risk of cognitive decline. Improved diet quality represents an important potential target for reducing the global burden of cognitive decline. PMID:25948720

Cross-linked fibrin degradation products (D-dimer), plasma cytokines, and cognitive decline in community-dwelling elderly persons.

PubMed

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.

Cohort Differences in Cognitive Aging in the Longitudinal Aging Study Amsterdam.

PubMed

Brailean, Anamaria; Huisman, Martijn; Prince, Martin; Prina, A Matthew; Deeg, Dorly J H; Comijs, Hannie

2016-09-30

This study aims to examine cohort differences in cognitive performance and rates of change in episodic memory, processing speed, inductive reasoning, and general cognitive performance and to investigate whether these cohort effects may be accounted for by education attainment. The first cohort (N = 705) was born between 1920 and 1930, whereas the second cohort (N = 646) was born between 1931 and 1941. Both birth cohorts were aged 65 to 75 years at baseline and were followed up 3 and 6 years later. Data were analyzed using linear mixed models. The later born cohort had better general cognitive performance, inductive reasoning, and processing speed at baseline, but cohort differences in inductive reasoning and general cognitive performance disappeared after adjusting for education. The later born cohort showed steeper decline in processing speed. Memory decline was steeper in the earlier born cohort but only from Time 1 to Time 3 when the same memory test was administered. Education did not account for cohort differences in cognitive decline. The later born cohort showed better initial performance in certain cognitive abilities, but no better preservation of cognitive abilities overtime compared with the earlier born cohort. These findings carry implications for healthy cognitive aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

Recognition of Famous Names Predicts Episodic Memory Decline in Cognitively Intact Elders

PubMed Central

Seidenberg, Michael; Kay, Christina; Woodard, John L.; Nielson, Kristy A.; Smith, J. Carson; Kandah, Cassandra; Guidotti Breting, Leslie M.; Novitski, Julia; Lancaster, Melissa; Matthews, Monica; Hantke, Nathan; Butts, Alissa; Rao, Stephen M.

2013-01-01

Objective: Semantic memory impairment is common in both Mild Cognitive Impairment (MCI) and early Alzheimer’s disease (AD), and the ability to recognize familiar people is particularly vulnerable. A time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently is also reported in both AD and MCI. In this study, we hypothesized that the TG pattern on a famous name recognition task (FNRT) administered to cognitively intact elders would predict future episodic memory decline, and would also show a significant correlation with hippocampal volume. Methods: 78 healthy elders (ages 65-90) with normal cognition and episodic memory at baseline were administered a FNRT. Follow-up episodic memory testing 18 months later produced two groups: Declining (≥ 1 SD reduction in episodic memory) and Stable (< 1 SD). Results: The Declining group (N=27) recognized fewer recent famous names than the Stable group (N=51), while recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampus was significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining versus Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: Famous name recognition may serve as an early pre-clinical cognitive marker of episodic memory decline in older individuals. PMID:23688215

The Cognitive Change Index as a Measure of Self and Informant Perception of Cognitive Decline: Relation to Neuropsychological Tests.

PubMed

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.

Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

PubMed

Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

2014-09-01

Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity.

SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β

PubMed Central

Cho, Seo-Hyun; Chen, Jason A.; Sayed, Faten; Ward, Michael E.; Gao, Fuying; Nguyen, Thi A.; Krabbe, Grietje; Sohn, Peter Dongmin; Lo, Iris; Minami, Sakura; Devidze, Nino; Zhou, Yungui; Coppola, Giovanni

2015-01-01

Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as the brain ages is an aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we report a mechanistic link between chronic inflammation and aging microglia and a causal role of aging microglia in neurodegenerative cognitive deficits. We showed that SIRT1 is reduced with the aging of microglia and that microglial SIRT1 deficiency has a causative role in aging- or tau-mediated memory deficits via IL-1β upregulation in mice. Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the specific CpG sites on IL-1β proximal promoter. In humans, hypomethylation of IL-1β is strongly associated with chronological age and with elevated IL-1β transcription. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in aging and neurodegenerative diseases. PMID:25589773

Hypertension is associated with cognitive decline in elderly people at high risk for dementia.

PubMed

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.

Patterns of brain atrophy associated with episodic memory and semantic fluency decline in aging.

PubMed

Pelletier, Amandine; Bernard, Charlotte; Dilharreguy, Bixente; Helmer, Catherine; Le Goff, Melanie; Chanraud, Sandra; Dartigues, Jean-François; Allard, Michèle; Amieva, Hélène; Catheline, Gwénaëlle

2017-03-09

The cerebral substratum of age-related cognitive decline was evaluated in an elderly-cohort followed for 12 years (n=306). Participants, free of dementia, received neuropsychological assessments every two years and an MRI exam at baseline and four years later. Cognitive decline was evaluated on two broadly used tests to detect dementia: the Free and Cued Selective Reminding Test (FCSRT), a verbal episodic memory task, and the Isaacs Set Test (IST), a semantic fluency task. Using voxel-based approach, the relationship between cognitive decline with 1/ baseline grey matter volumes and 2/ grey matter volume loss between the two scans was explored. Baseline volumes analysis revealed that FCSRT and IST declines were both associated with lower volumes of the medial temporal region. Volumes loss analysis confirmed that both declines are related to medial temporal lobe atrophy and revealed that FCSRT decline was specifically associated with atrophy of the posterior cingulate cortex whereas IST decline was specifically related to temporal pole atrophy. These results suggest that cognitive decline across aging is firstly related to structural modifications of the medial temporal lobe, followed by an atrophy in the posterior midline structures for episodic memory and an atrophy of the temporal pole for semantic fluency.

Functional network integrity presages cognitive decline in preclinical Alzheimer disease.

PubMed

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.

Subjective cognitive decline: self and informant comparisons.

PubMed

Caselli, Richard J; Chen, Kewei; Locke, Dona E C; Lee, Wendy; Roontiva, Auttawut; Bandy, Dan; Fleisher, Adam S; Reiman, Eric M

2014-01-01

It is unclear whether self- or informant-based subjective cognition better distinguishes emotional factors from early-stage Alzheimer's disease (AD). Healthy members (n = 447) of the Arizona apolipoprotein E (APOE) cohort and their informants completed the self and informant paired Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS). Decline on the MANS was endorsed by 30.6% of members and 26.2% of informants. Self- and informant-based decliners had higher scores of psychological distress and slightly lower cognitive scores than nondecliners. Over the next 6.7 years, 20 developed mild cognitive impairment (MCI). Converters were older at entry than nonconverters (63.8 [7.0] vs 58.8 [7.3] years, P = .003), 85% were APOE ε4 carriers (P < .0001), and they self-endorsed decline earlier than informants (58.9 [39.2] vs 28.0 [40.4] months before MCI; P = .002). Self- and informant-based subjective decline correlated with greater psychological distress and slightly lower cognitive performance. Those with incident MCI generally self-endorsed decline earlier than informants. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Longitudinal evaluation of criteria for subjective cognitive decline and preclinical Alzheimer's disease in a memory clinic sample.

PubMed

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.

Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort.

PubMed

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.

Age-related Effects on Word Recognition: Reliance on Cognitive Control Systems with Structural Declines in Speech-responsive Cortex

PubMed Central

Walczak, Adam; Ahlstrom, Jayne; Denslow, Stewart; Horwitz, Amy; Dubno, Judy R.

2008-01-01

Speech recognition can be difficult and effortful for older adults, even for those with normal hearing. Declining frontal lobe cognitive control has been hypothesized to cause age-related speech recognition problems. This study examined age-related changes in frontal lobe function for 15 clinically normal hearing adults (21–75 years) when they performed a word recognition task that was made challenging by decreasing word intelligibility. Although there were no age-related changes in word recognition, there were age-related changes in the degree of activity within left middle frontal gyrus (MFG) and anterior cingulate (ACC) regions during word recognition. Older adults engaged left MFG and ACC regions when words were most intelligible compared to younger adults who engaged these regions when words were least intelligible. Declining gray matter volume within temporal lobe regions responsive to word intelligibility significantly predicted left MFG activity, even after controlling for total gray matter volume, suggesting that declining structural integrity of brain regions responsive to speech leads to the recruitment of frontal regions when words are easily understood. Electronic supplementary material The online version of this article (doi:10.1007/s10162-008-0113-3) contains supplementary material, which is available to authorized users. PMID:18274825

Fasting insulin levels and cognitive decline in older women without diabetes.

PubMed

van Oijen, Marieke; Okereke, Olivia I; Kang, Jae Hee; Pollak, Michael N; Hu, Frank B; Hankinson, Susan E; Grodstein, Francine

2008-01-01

Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses' Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70-75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, -0.06 (-0.16, 0.03), -0.14 (-0.24, -0.04), and -0.09 (-0.19, 0.01) points (p trend = 0.04); verbal memory, -0.01 (-0.04, 0.02), -0.05 (-0.08, -0.02), and -0.02 (-0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes. (c) 2008 S. Karger AG, Basel

Genetic influences on cognitive decline in Parkinson's disease

PubMed Central

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

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS

PubMed Central

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

Age identity, gender, and perceptions of decline: does feeling older lead to pessimistic dispositions about cognitive aging?

PubMed

Schafer, Markus H; Shippee, Tetyana P

2010-01-01

Drawing on past studies of age identity, this article examined whether feeling older was associated with more pessimistic views about cognitive aging. Using respondents aged 55 years and older in the Midlife Development in the United States study, we estimated a series of linear regression models to predict people's dispositions toward their cognitive aging. The main comparison is whether the effects of age identity on cognitive aging differ for men and women. Beyond the effects of chronological age, older age identities were associated with more pessimistic dispositions about cognitive aging. This relationship, however, was found only among women. Age identity shapes cognitive aging dispositions, though the gendered nature of this relationship remains somewhat unclear. The findings give further evidence about the far-reaching implications of age identity for successful aging and suggest that future work can explicate how subjective aging processes may differ by gender.

Role of APOE ε4 Allele and Incident Stroke on Cognitive Decline and Mortality.

PubMed

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.

The association between cognitive decline and incident depressive symptoms in a sample of older Puerto Rican adults with diabetes.

PubMed

Bell, Tyler; Dávila, Ana Luisa; Clay, Olivio; Markides, Kyriakos S; Andel, Ross; Crowe, Michael

2017-08-01

Older Puerto Rican adults have particularly high risk of diabetes compared to the general US population. Diabetes is associated with both higher depressive symptoms and cognitive decline, but less is known about the longitudinal relationship between cognitive decline and incident depressive symptoms in those with diabetes. This study investigated the association between cognitive decline and incident depressive symptoms in older Puerto Rican adults with diabetes over a four-year period. Households across Puerto Rico were visited to identify a population-based sample of adults aged 60 years and over for the Puerto Rican Elderly: Health Conditions study (PREHCO); 680 participants with diabetes at baseline and no baseline cognitive impairment were included in analyses. Cognitive decline and depressive symptoms were measured using the Mini-Mental Cabán (MMC) and Geriatric Depression Scale (GDS), respectively. We examined predictors of incident depressive symptoms (GDS ≥ 5 at follow-up but not baseline) and cognitive decline using regression modeling. In a covariate-adjusted logistic regression model, cognitive decline, female gender, and greater diabetes-related complications were each significantly associated with increased odds of incident depressive symptoms (p < 0.05). In a multiple regression model adjusted for covariates, incident depressive symptoms and older age were associated with greater cognitive decline, and higher education was related to less cognitive decline (p < 0.05). Incident depressive symptoms were more common for older Puerto Ricans with diabetes who also experienced cognitive decline. Efforts are needed to optimize diabetes management and monitor for depression and cognitive decline in this population.

Diabetes, impaired fasting glucose, and cognitive decline in a population of elderly community residents.

PubMed

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.

Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

PubMed Central

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

Association Between Cognitive Decline in Older Adults and Utilization of Primary Care Physician Services in Pennsylvania

PubMed Central

Fowler, Nicole R.; Morrow, Lisa A.; Tu, Li-Chuan; Landsittel, Douglas P.; Snitz, Beth E.; Rodriquez, Eric G.; Saxton, Judith A.

2012-01-01

OBJECTIVE To assess the relationship between cognitive decline of older patients (≥65 years) and utilization of primary care physician (PCP) services over 24-months. DESIGN Retrospective analysis of prospectively collected data from a cluster randomized trial that took place from 2006 to 2010 and investigated the relationship between formal neuropsychological evaluation and patient outcomes in primary care. SETTING Twenty-four PCPs in 11 practices in southwestern Pennsylvania. Most practices were suburban and included more than 5 PCPs. PARTICIPANTS A sample of 423 primary care patients 65 years or older. MEASUREMENTS The association between the number of PCP visits and a decline in cognitive status, as determined by multivariable analyses that controlled for patient-level, physician-level, and practice-level factors (e.g., patient age, comorbidities, and symptoms of depression; practice location and size; PCP age and sex) and used a linear mixed model with a random intercept to adjust for clustering. RESULTS Over a two year follow-up, 199 patients (47.0%) experienced a decline in cognitive status. Patients with a cognitive decline had a mean of 0.69 more PCP visits than did patients without a cognitive decline (P<0.05). CONCLUSIONS Early signs of cognitive decline may be an indicator of greater utilization of primary care. Given the demographic trends, more PCPs are likely to be needed to meet the increasing needs of the older population. PMID:22798988

Brain volume change and cognitive trajectories in aging.

PubMed

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).

Neighbourhood racial/ethnic composition and segregation and trajectories of cognitive decline among US older adults.

PubMed

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.

Neighborhoods, sleep quality, and cognitive decline: Does where you live and how well you sleep matter?

PubMed

Hunter, Jaimie C; Handing, Elizabeth P; Casanova, Ramon; Kuchibhatla, Maragatha; Lutz, Michael W; Saldana, Santiago; Plassman, Brenda L; Hayden, Kathleen M

2018-04-01

We evaluated the association between neighborhood socioeconomic status (NSES) and sleep quality on cognitive decline in the Health and Retirement Study. Health and Retirement Study participants (n = 8090), aged 65+ with DNA and multiple biennial cognitive observations (abbreviated Telephone Interview for Cognitive Status), were included. Participants were grouped into quartiles of NSES and sleep quality scores. We adjusted for apolipoprotein E ε4, demographic, and cardiovascular risk factors. Random effects modeling evaluated cognitive change over time. NSES and sleep were significantly associated with cognitive decline, and there was a significant interaction between them (P = .02). Significant differences between high/low NSES and high/low sleep quality (P < .0001) were found. Sleep and NSES were associated with cognitive decline; the association between sleep and cognition appeared stronger among those with low NSES. The association between low NSES, poor sleep quality, and cognitive decline was roughly equivalent to the association between apolipoprotein E ε4 and cognitive decline. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife

PubMed Central

Racine, Annie M.; Koscik, Rebecca L.; Berman, Sara E.; Nicholas, Christopher R.; Clark, Lindsay R.; Okonkwo, Ozioma C.; Rowley, Howard A.; Asthana, Sanjay; Bendlin, Barbara B.; Blennow, Kaj; Zetterberg, Henrik; Gleason, Carey E.; Carlsson, Cynthia M.

2016-01-01

The ability to detect preclinical Alzheimer’s disease is of great importance, as this stage of the Alzheimer’s continuum is believed to provide a key window for intervention and prevention. As Alzheimer’s disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer’s disease; (ii) mixed Alzheimer’s disease and vascular aetiology; (iii) suspected non-Alzheimer’s disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal

Tooth loss associated with physical and cognitive decline in older adults.

PubMed

Tsakos, Georgios; Watt, Richard G; Rouxel, Patrick L; de Oliveira, Cesar; Demakakos, Panayotes

2015-01-01

To examine the effect of total tooth loss (edentulousness) on decline in physical and cognitive functioning over 10 years in older adults in England. Secondary data analysis. English Longitudinal Study of Ageing, a national prospective cohort study of community-dwelling people aged 50 and older. Individuals aged 60 and older (N = 3,166). Cognitive function (memory) was measured using a 10-word recall test. Physical function was assessed using gait speed (m/s). Generalized estimating equations were used to model associations between baseline edentulousness and six repeated measurements of gait speed and memory from 2002-03 to 2012-13. Models were sequentially adjusted for time, demographic characteristics, socioeconomic status, comorbidities, health behaviors, depressive symptoms, and anthropometric measurements and mutually adjusted for gait speed or memory. Edentulous participants recalled 0.88 fewer words and were 0.09 m/s slower than dentate participants after adjusting for time and demographics. Only the latter association remained significant after full adjustment, with edentulous participants being 0.02 m/s slower than dentate participants. In age-stratified analyses, baseline edentulousness was associated with both outcomes in fully adjusted models in participants aged 60 to 74 but not in those aged 75 and older. Supplementary analysis indicated significant associations between baseline edentulousness and 4-year change in gait speed and memory in participants aged 60 to 74; the former was fully explained in the fully adjusted model and the latter after adjusting for socioeconomic status. Total tooth loss was independently associated with physical and cognitive decline in older adults in England. Tooth loss is a potential early marker of decline in older age. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Association of Long-Term Adherence to the MIND Diet with Cognitive Function and Cognitive Decline in American Women.

PubMed

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.

Dietary enrichment counteracts age-associated cognitive dysfunction in canines.

PubMed

Milgram, N W; Zicker, S C; Head, E; Muggenburg, B A; Murphey, H; Ikeda-Douglas, C J; Cotman, C W

2002-01-01

Advanced age is accompanied by cognitive decline indicative of central nervous system dysfunction. One possibly critical causal factor is oxidative stress. Accordingly, we studied the effects of dietary antioxidants and age in a canine model of aging that parallels the key features of cognitive decline and neuropathology in humans. Old and young animals were placed on either a standard control food, or a food enriched with a broad spectrum of antioxidants and mitochondrial enzymatic cofactors. After 6 months of treatment, the animals were tested on four increasingly difficult oddity discrimination learning problems. The old animals learned more slowly than the young, making significantly more errors. However, this age-associated decline was reduced in the animals fed the enriched food, particularly on the more difficult tasks. These results indicate that maintenance on foods fortified with complex mixtures of antioxidants can partially counteract the deleterious effects of aging on cognition. Copyright 2002 Elsevier Science Inc.

Gray matter network measures are associated with cognitive decline in mild cognitive impairment.

PubMed

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.

Predicting the Rate of Cognitive Decline in Alzheimer Disease: Data From the ICTUS Study.

PubMed

Canevelli, Marco; Kelaiditi, Eirini; Del Campo, Natalia; Bruno, Giuseppe; Vellas, Bruno; Cesari, Matteo

2016-01-01

Different rates of cognitive progression have been observed among Alzheimer disease (AD) patients. The present study aimed at evaluating whether the rate of cognitive worsening in AD may be predicted by widely available and easy-to-assess factors. Mild to moderate AD patients were recruited in the ICTUS study. Multinomial logistic regression analysis was performed to measure the association between several sociodemographic and clinical variables and 3 different rates of cognitive decline defined by modifications (after 1 year of follow-up) of the Mini Mental State Examination (MMSE) score: (1) "slow" progression, as indicated by a decrease in the MMSE score ≤1 point; (2) "intermediate" progression, decrease in the MMSE score between 2 and 5 points; and (3) "rapid" progression, decrease in the MMSE score ≥6 points. A total of 1005 patients were considered for the present analyses. Overall, most of the study participants (52%) exhibited a slow cognitive course. Higher ADAS-Cog scores at baseline were significantly associated with both "intermediate" and "rapid" decline. Conversely, increasing age was negatively associated with "rapid" cognitive worsening. A slow progression of cognitive decline is common among AD patients. The influence of age and baseline cognitive impairment should always be carefully considered when designing AD trials and defining study populations.

Fasting Insulin Levels and Cognitive Decline in Older Women without Diabetes

PubMed Central

van Oijen, Marieke; Okereke, Olivia I.; Kang, Jae Hee; Pollak, Michael N.; Hu, Frank B.; Hankinson, Susan E.; Grodstein, Francine

2008-01-01

Background Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. Methods Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses’ Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70–75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. Results Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, −0.06 (−0.16, 0.03), −0.14 (−0.24, −0.04), and −0.09 (−0.19, 0.01) points (p trend = 0.04); verbal memory, −0.01 (−0.04, 0.02), −0.05 (−0.08, −0.02), and −0.02 (−0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. Conclusions Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes. PMID:18421217

Effects of education and race on cognitive decline: An integrative analysis of generalizability versus study-specific results

PubMed Central

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

Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results.

PubMed

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).

BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention

PubMed Central

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.

PubMed

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.

Complementary cognitive capabilities, economic decision making, and aging.

PubMed

Li, Ye; Baldassi, Martine; Johnson, Eric J; Weber, Elke U

2013-09-01

Fluid intelligence decreases with age, yet evidence about age declines in decision-making quality is mixed: Depending on the study, older adults make worse, equally good, or even better decisions than younger adults. We propose a potential explanation for this puzzle, namely that age differences in decision performance result from the interplay between two sets of cognitive capabilities that impact decision making, one in which older adults fare worse (i.e., fluid intelligence) and one in which they fare better (i.e., crystallized intelligence). Specifically, we hypothesized that older adults' higher levels of crystallized intelligence can provide an alternate pathway to good decisions when the fluid intelligence pathway declines. The performance of older adults relative to younger adults therefore depends on the relative importance of each type of intelligence for the decision at hand. We tested this complementary capabilities hypothesis in a broad sample of younger and older adults, collecting a battery of standard cognitive measures and measures of economically important decision-making "traits"--including temporal discounting, loss aversion, financial literacy, and debt literacy. We found that older participants performed as well as or better than younger participants on these four decision-making measures. Structural equation modeling verified our hypothesis: Older participants' greater crystallized intelligence offset their lower levels of fluid intelligence for temporal discounting, financial literacy, and debt literacy, but not for loss aversion. These results have important implications for public policy and for the design of effective decision environments for older adults.

Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

ERIC Educational Resources Information Center

Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

2008-01-01

A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

Exercise, cognitive function, and aging

PubMed Central

2015-01-01

Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise. PMID:26031719

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women's Health Initiative Memory Study.

PubMed

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.

Entorhinal Tau Pathology, Episodic Memory Decline, and Neurodegeneration in Aging.

PubMed

Maass, Anne; Lockhart, Samuel N; Harrison, Theresa M; Bell, Rachel K; Mellinger, Taylor; Swinnerton, Kaitlin; Baker, Suzanne L; Rabinovici, Gil D; Jagust, William J

2018-01-17

The medial temporal lobe (MTL) is an early site of tau accumulation and MTL dysfunction may underlie episodic-memory decline in aging and dementia. Postmortem data indicate that tau pathology in the transentorhinal cortex is common by age 60, whereas spread to neocortical regions and worsening of cognition is associated with β-amyloid (Aβ). We used [ 18 F]AV-1451 and [ 11 C]PiB positron emission tomography, structural MRI, and neuropsychological assessment to investigate how in vivo tau accumulation in temporal lobe regions, Aβ, and MTL atrophy contribute to episodic memory in cognitively normal older adults ( n = 83; age, 77 ± 6 years; 58% female). Stepwise regressions identified tau in MTL regions known to be affected in old age as the best predictor of episodic-memory performance independent of Aβ status. There was no interactive effect of MTL tau with Aβ on memory. Higher MTL tau was related to higher age in the subjects without evidence of Aβ. Among temporal lobe subregions, episodic memory was most strongly related to tau-tracer uptake in the parahippocampal gyrus, particularly the posterior entorhinal cortex, which in our parcellation includes the transentorhinal cortex. In subjects with longitudinal MRI and cognitive data ( n = 57), entorhinal atrophy mirrored patterns of tau pathology and their relationship with memory decline. Our data are consistent with neuropathological studies and further suggest that entorhinal tau pathology underlies memory decline in old age even without Aβ. SIGNIFICANCE STATEMENT Tau tangles and β-amyloid (Aβ) plaques are key lesions in Alzheimer's disease (AD) but both pathologies also occur in cognitively normal older people. Neuropathological data indicate that tau tangles in the medial temporal lobe (MTL) underlie episodic-memory impairments in AD dementia. However, it remains unclear whether MTL tau pathology also accounts for memory impairments often seen in elderly people and how Aβ affects this relationship

Functional neuroimaging of normal aging: Declining brain, adapting brain.

PubMed

Sugiura, Motoaki

2016-09-01

Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive and motor aging in female chimpanzees.

PubMed

Lacreuse, Agnès; Russell, Jamie L; Hopkins, William D; Herndon, James G

2014-03-01

We present the first longitudinal data on cognitive and motor aging in the chimpanzee (Pan troglodytes). Thirty-eight adult female chimpanzees (10-54 years old) were studied. The apes were tested longitudinally for 3 years in a modified Primate Cognition Test Battery, which comprised 12 tests of physical and social cognition. The chimpanzees were also administered a fine motor task requiring them to remove a steel nut from rods of various complexity. There was little evidence for an age-related decline in tasks of Physical Cognition: for most tasks, performance was either stable or improved with repeated testing across age groups. An exception was Spatial Memory, for which 4 individuals more than 50 years old experienced a significant performance decline across the 3 years of testing. Poorer performance with age was found in 2 tasks of Social Cognition, an attention-getting task and a gaze-following task. A slight motor impairment was also observed, with old chimpanzees improving less than younger animals with repeated testing on the simplest rod. Hormonal status effects were restricted to spatial memory, with non-cycling females outperforming cycling females independently of age. Unexpectedly, older chimpanzees were better than younger individuals in understanding causality relationships based on sound. Copyright © 2014 Elsevier Inc. All rights reserved.

Gait Rather Than Cognition Predicts Decline in Specific Cognitive Domains in Early Parkinson's Disease.

PubMed

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.

Cerebral microbleeds are associated with cognitive decline and dementia: the Rotterdam Study

PubMed Central

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

Longitudinal Modeling of Functional Decline Associated with Pathologic Alzheimer's Disease in Older Persons without Cognitive Impairment.

PubMed

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.

Plasma cytokine IL-6 levels and subjective cognitive decline: preliminary findings.

PubMed

Keegan, Andrew P; Paris, Daniel; Luis, Cheryl A; Abdullah, Laila; Ait-Ghezala, Ghania; Beaulieu-Abdelahad, David; Pryor, Makenzie; Chaykin, Jillian; Crynen, Gogce; Crawford, Fiona; Mullan, Michael

2018-02-01

Detection of Alzheimer's disease (AD) prior to clinical inception will be paramount for introducing disease modifying treatments. We have begun collecting baseline characteristics of a community cohort for longitudinal assessment and testing of antecedent blood-based biomarkers. We describe the baseline visit from the first 131 subjects in relationship to a commonly described cytokine, interleukin 6 (IL-6). Subjects from the community presented for a free memory screening with varying degrees of memory concern. We quantified the baseline plasma levels of the cytokine IL-6 and assessed cognition (Montreal Cognitive Assessment, MoCA) and mood (Geriatric Depression Scale, GDS) in relationship to their memory concern. Baseline MoCA scores were inversely related to age, and this association was influenced by an AD risk factor, Apolipoprotein E (APOE4) carrier status. The degree of subjective cognitive decline correlated with GDS and was inversely related to MoCA scores. Interleukin 6 levels were related to age, body mass index, and years of education. It will be important to assess how these baseline IL-6 levels and forthcoming novel biomarkers relate to future cognitive decline. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Roles of Arterial Stiffness and Blood Pressure in Hypertension-Associated Cognitive Decline in Healthy Adults.

PubMed

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.

Longitudinal cognitive decline in the AIBL cohort: The role of APOE ε4 status.

PubMed

Albrecht, Matthew A; Szoeke, Cassandra; Maruff, Paul; Savage, Greg; Lautenschlager, Nicola T; Ellis, Kathryn A; Taddei, Kevin; Martins, Ralph; Masters, Colin L; Ames, David; Foster, Jonathan K

2015-08-01

The ε4 polymorphism of the APOE gene confers a substantially increased risk of developing Alzheimer's disease. However, the influence of the ε4 allele on age-related cognitive functioning is more contentious. Previously, we demonstrated relatively little evidence for a role of the ε4 allele on baseline cognitive performance in older adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing (Foster et al., 2013). We here investigated whether the APOE ε4 allele influenced cognitive status over time when the AIBL cohort was studied longitudinally over a 3-year period. The AIBL neuropsychological test battery was administered at baseline, after 18 months and again after 36 months. Participants comprised 764 Healthy Controls and 131 Mild Cognitively Impaired individuals enrolled in the AIBL Study of Ageing. We compared individuals within each group with and without an ε4 allele. Healthy Controls with an ε4 allele manifested a modest acceleration in cognitive decline over 36 months on measures of verbal episodic memory. By contrast, Mild Cognitively Impaired individuals with an ε4 allele showed increased cognitive decline across a range of cognitive tasks, putatively reflecting early cognitive signs of Alzheimer's disease. Given the long prodromal period that has been noted in late onset Alzheimer's disease, we suggest that these findings are consistent with a prodromal account rather than a phenotypic account of ε4-related cognitive ageing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

PubMed

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

Bereavement and behavioral changes as risk factors for cognitive decline in adults with Down syndrome.

PubMed

Fonseca, Luciana Mascarenhas; de Oliveira, Melaine Cristina; de Figueiredo Ferreira Guilhoto, Laura Maria; Cavalheiro, Esper Abrao; Bottino, Cássio Mc

2014-01-01

Cognitive decline and Alzheimer's disease often affect older adults with Down syndrome (DS) much earlier than those in the general population. There is also growing evidence of the effects of negative life events on the mental health and behavior of individuals with intellectual disability. However, to our knowledge, this is the first study investigating objective cognitive decline following bereavement in aging individuals with DS. The objective of this study was to determine whether cognitive decline correlates with bereavement following the recent loss of a caregiver or with behavioral changes in a sample of adult individuals with DS who do not meet the criteria for dementia or depression, using the longitudinal assessment of the Cambridge Cognitive Examination (CAMCOG), together with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We evaluated 18 subjects at baseline and over a follow-up period of 14-22 months, attempting to determine whether cognitive decline correlates with bereavement following the recent loss of the main caregiver or with behavioral changes (as assessed with the Neuropsychiatric Inventory). The mean rate of change in CAMCOG was -1.83 (standard deviation 4.51). Behavioral changes had a significant direct influence on cognitive decline. When bereavement was accompanied by behavioral changes, the probability of cognitive decline was 87% (odds ratio 3.82). The occurrence of behavioral changes attributed to bereavement following the loss of the primary caregiver significantly increases the probability of cognitive decline in individuals with DS. Longitudinal comparison of the CAMCOG and use of the IQCODE appear to enrich the analysis of cognitive decline in individuals with DS. Further studies involving larger samples are needed in order to corroborate and expand upon our findings, which can have implications for the clinical management of older adults with DS.

Identifying elderly people at risk for cognitive decline by using the 2-step test.

PubMed

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.

Midlife C-reactive protein and risk of cognitive decline: a 31-year follow-up.

PubMed

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.

Bilingualism does not alter cognitive decline or dementia risk among Spanish-speaking immigrants.

PubMed

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

PubMed Central

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

Cognitive decline and survival in Alzheimer's disease according to education level.

PubMed

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 (12 years). Cognitive function was measured with the Mini Mental State Examination (MMSE) and the Mattis Dementia Rating Scale (DRS). Survival was analyzed with a Cox model. Analyses were adjusted for age, sex, cholinesterase inhibitor treatment, diabetes, hypertension, visible vascular lesions on MRI, baseline DRS and MMSE. The adjusted mixed random model showed that MMSE declined faster for patients with high and intermediate educational levels compared with those with a low educational level (p < 0.0001). The mean annually adjusted DRS decline was highest for the groups with the most education (p = 0.05). The mortality risk was not higher in the better-educated groups (high vs. low: RR = 0.84; 95% CI = 0.35-1.99, intermediate vs. low: RR = 0.82; 95% CI = 0.41-1.63). In our cohort, highly educated patients had a faster cognitive decline than less educated patients but similar mortality rates. Our findings support the cognitive reserve hypothesis. (c) 2007 S. Karger AG, Basel.

Terminal-decline effects for select cognitive tasks after controlling for preclinical dementia.

PubMed

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.

Does physical activity prevent cognitive decline and dementia?: A systematic review and meta-analysis of longitudinal studies

PubMed Central

2014-01-01

Background By 2050, it has been estimated that approximately one-fifth of the population will be made up of older adults (aged ≥60 years). Old age often comes with cognitive decline and dementia. Physical activity may prevent cognitive decline and dementia. Methods We reviewed and synthesised prospective studies into physical activity and cognitive decline, and physical activity and dementia, published until January 2014. Forty-seven cohorts, derived from two previous systematic reviews and an updated database search, were used in the meta-analyses. Included participants were aged ≥40 years, in good health and/or randomly selected from the community. Studies were assessed for methodological quality. Results Twenty-one cohorts on physical activity and cognitive decline and twenty-six cohorts on physical activity and dementia were included. Meta-analysis, using the quality-effects model, suggests that participants with higher levels of physical activity, when compared to those with lower levels, are at reduced risk of cognitive decline, RR 0.65, 95% CI 0.55-0.76, and dementia, RR 0.86, 95% CI 0.76-0.97. Sensitivity analyses revealed a more conservative estimate of the impact of physical activity on cognitive decline and dementia for high quality studies, studies reporting effect sizes as ORs, greater number of adjustments (≥10), and longer follow-up time (≥10 years). When one heavily weighted study was excluded, physical activity was associated with an 18% reduction in the risk of dementia (RR 0.82; 0.73-0.91). Conclusions Longitudinal observational studies show an association between higher levels of physical activity and a reduced risk of cognitive decline and dementia. A case can be made for a causal interpretation. Future research should use objective measures of physical activity, adjust for the full range of confounders and have adequate follow-up length. Ideally, randomised controlled trials will be conducted. Regardless of any effect on cognition

 Cortical Atrophy is Associated with Accelerated Cognitive Decline in Mild Cognitive Impairment with Subsyndromal Depression.

PubMed

Gonzales, Mitzi M; Insel, Philip S; Nelson, Craig; Tosun, Duygu; Mattsson, Niklas; Mueller, Susanne G; Sacuiu, Simona; Bickford, David; Weiner, Michael W; Mackin, R Scott

2017-09-01

To investigate the association between cognitive decline and cortical atrophy in individuals with mild cognitive impairment (MCI) and chronic subsyndromal symptoms of depression (SSD) over a 4-year period. Prospective cohort study. Multicenter, clinic-based. Within the Alzheimer's Disease Neuroimaging Initiative repository, the Neuropsychiatric Inventory was used to identify individuals with MCI and stable endorsement (SSD group N = 32) or no endorsement (non-SSD group N = 69) of depressive symptoms across time points. Repeated measures of cognitive outcomes, cortical atrophy, and their associations were evaluated with mixed effects models adjusting for age, education, sex, and APOE genotype. The SSD group demonstrated accelerated decline on measures of global cognition (Alzheimer Disease Assessment Scale; df = 421, t = 2.242, p = 0.025), memory (Wechsler Memory Scale-Revised Logical Memory II; df = 244, t = -2.525, p = 0.011), information processing speed (Trail Making Test Parts A [df = 421, t = 2.376, p = 0.018] and B [df = 421, t = 2.533, p = 0.012]), and semantic fluency (Category Fluency; df = 424, t = -2.418, p = 0.016), as well as accelerated frontal lobe (df = 341, t = -2.648, p = 0.008) and anterior cingulate (df = 341, t = -3.786, p < 0.001) atrophy. No group differences were observed for rate of decline on measures of attention, learning, and confrontation naming or for rate of atrophy in any other regions. Accelerated frontal lobe and anterior cingulate atrophy was associated with cognitive decline on measures of global cognition, information processing speed, and semantic fluency (all p < 0.05), but not memory. Individuals with chronic SSD may represent an MCI subgroup that is highly vulnerable to accelerated cognitive decline, an effect that may be governed by frontal lobe and anterior cingulate atrophy. Published by Elsevier Inc.

Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function.

PubMed

McBride, Sean M J; Choi, Catherine H; Schoenfeld, Brian P; Bell, Aaron J; Liebelt, David A; Ferreiro, David; Choi, Richard J; Hinchey, Paul; Kollaros, Maria; Terlizzi, Allison M; Ferrick, Neal J; Koenigsberg, Eric; Rudominer, Rebecca L; Sumida, Ai; Chiorean, Stephanie; Siwicki, Kathleen K; Nguyen, Hanh T; Fortini, Mark E; McDonald, Thomas V; Jongens, Thomas A

2010-07-14

Alzheimer's disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced.

An 18-mo randomized, double-blind, placebo-controlled trial of DHA-rich fish oil to prevent age-related cognitive decline in cognitively normal older adults.

PubMed

Danthiir, Vanessa; Hosking, Diane E; Nettelbeck, Ted; Vincent, Andrew D; Wilson, Carlene; O'Callaghan, Nathan; Calvaresi, Eva; Clifton, Peter; Wittert, Gary A

2018-05-01

Fish oil trials in cognitively healthy older adults have yielded inconsistent results. Supplementation may differentially affect the domains that underpin cognitive performance, and effects may differ across sex or genotype. The aim of this study was to test whether docosahexaenoic acid (DHA)-rich fish oil slows 18-mo cognitive decline in cognitively healthy elders. In a double-blind, randomized, placebo-controlled, parallel-group trial, cognitively healthy Australian community-dwelling adults (aged 65-90 y) consumed either 1720 mg DHA and 600 mg eicosapentaenoic acid or low-polyphenolic olive oil daily, as capsules, for 18 mo. Groups were allocated by permuted-block randomization and stratified by age. Cognitive assessment was conducted at baseline and then every 6 mo. Primary analyses tested the difference between groups in the rate of 18-mo cognitive change via latent growth curve models on any of the following: reasoning, working memory, short-term memory, retrieval fluency, and cognitive speed-related constructs. Treatment interactions with sex and APOE-ε4 were tested. Secondary outcomes were self-reported changes in well-being and everyday functioning, blood pressure, biomarkers of n-3 (ω-3) long-chain polyunsaturated fatty acids (LC PUFAs), lipids, glucose metabolism, inflammation, oxidative stress, DNA damage, and Mini-Mental State Examination. A total of 403 people were randomly assigned. Data from those who completed baseline were analyzed (n = 390; intervention n = 194, control n = 196). Daily supplementation with 2.3 g DHA-rich fish oil for 18 mo did not maintain or improve cognitive performance. A small negative main effect was found on psychomotor speed (intervention = -0.02, 95% CI: -0.04 to 0.00; d = 0.24, P = 0.03). Treatment effects differed according to sex on retrieval fluency and some speed-based domains, including psychomotor speed, and according to APOE-ε4 carrier status on reaction time and reasoning. For secondary outcomes

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery.

PubMed

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

Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife.

PubMed

Racine, Annie M; Koscik, Rebecca L; Berman, Sara E; Nicholas, Christopher R; Clark, Lindsay R; Okonkwo, Ozioma C; Rowley, Howard A; Asthana, Sanjay; Bendlin, Barbara B; Blennow, Kaj; Zetterberg, Henrik; Gleason, Carey E; Carlsson, Cynthia M; Johnson, Sterling C

2016-08-01

The ability to detect preclinical Alzheimer's disease is of great importance, as this stage of the Alzheimer's continuum is believed to provide a key window for intervention and prevention. As Alzheimer's disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer's disease; (ii) mixed Alzheimer's disease and vascular aetiology; (iii) suspected non-Alzheimer's disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our

Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.

PubMed

Bernick, Charles; Cummings, Jeffrey; Raman, Rema; Sun, Xiaoying; Aisen, Paul

2012-07-01

Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. To determine the influence of age on AD course in a clinical trial setting. Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Alzheimer disease research centers from across the United States. Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

Hypertension, Dietary Sodium, and Cognitive Decline: Results From the Women’s Health Initiative Memory Study

PubMed Central

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

Plasma Klotho and Cognitive Decline in Older Adults: Findings From the InCHIANTI Study

PubMed Central

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

Complementary Cognitive Capabilities, Economic Decision-Making, and Aging

PubMed Central

Li, Ye; Baldassi, Martine; Johnson, Eric J.; Weber, Elke U.

2014-01-01

Fluid intelligence decreases with age, yet evidence about age declines in decision-making quality is mixed: Depending on the study, older adults make worse, equally good, or even better decisions than younger adults. We propose a potential explanation for this puzzle, namely that age differences in decision performance result from the interplay between two sets of cognitive capabilities that impact decision making, one in which older adults fare worse (i.e., fluid intelligence) and one in which they fare better (i.e., crystallized intelligence). Specifically, we hypothesized that older adults’ higher levels of crystallized intelligence can provide an alternate pathway to good decisions when the fluid intelligence pathway declines. The performance of older adults relative to younger adults therefore depends on the relative importance of each type of intelligence for the decision at hand. We tested this complementary capabilities hypothesis in a broad sample of younger and older adults, collecting a battery of standard cognitive measures and measures of economically important decision-making “traits”—including temporal discounting, loss aversion, financial literacy, and debt literacy. We found that older participants performed as well as or better than younger participants on these four decision-making measures. Structural equation modeling verified our hypothesis: Older participants’ greater crystallized intelligence offset their lower levels of fluid intelligence for temporal discounting, financial literacy, and debt literacy, but not for loss aversion. These results have important implications for public policy and for the design of effective decision environments for older adults. PMID:24040999

Aging, Cognitive Decline and Hearing Loss: Effects of Auditory Rehabilitation and Training with Hearing Aids and Cochlear Implants on Cognitive Function and Depression among Older Adults.

PubMed

Castiglione, Alessandro; Benatti, Alice; Velardita, Carmelita; Favaro, Diego; Padoan, Elisa; Severi, Daniele; Pagliaro, Michela; Bovo, Roberto; Vallesi, Antonino; Gabelli, Carlo; Martini, Alessandro

2016-01-01

A growing interest in cognitive effects associated with speech and hearing processes is spreading throughout the scientific community essentially guided by evidence that central and peripheral hearing loss is associated with cognitive decline. For the present research, 125 participants older than 65 years of age (105 with hearing impairment and 20 with normal hearing) were enrolled, divided into 6 groups according to their degree of hearing loss and assessed to determine the effects of the treatment applied. Patients in our research program routinely undergo an extensive audiological and cognitive evaluation protocol providing results from the Digit Span test, Stroop color-word test, Montreal Cognitive Assessment and Geriatric Depression Scale, before and after rehabilitation. Data analysis was performed for a cross-sectional and longitudinal study of the outcomes for the different treatment groups. Each group demonstrated improvement after auditory rehabilitation or training on short- and long-term memory tasks, level of depression and cognitive status scores. Auditory rehabilitation by cochlear implants or hearing aids is effective also among older adults (median age of 74 years) with different degrees of hearing loss, and enables positive improvements in terms of social isolation, depression and cognitive performance. © 2016 The Author(s) Published by S. Karger AG, Basel.

Reversal of cognitive decline in Alzheimer's disease

PubMed Central

Bredesen, Dale E.; Amos, Edwin C.; Canick, Jonathan; Ackerley, Mary; Raji, Cyrus; Fiala, Milan; Ahdidan, Jamila

2016-01-01

Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4−, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype. PMID:27294343

Cognitive Decline in Older Persons Initiating Anticholinergic Medications

PubMed Central

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

A more randomly organized grey matter network is associated with deteriorating language and global cognition in individuals with subjective cognitive decline.

PubMed

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

Relation between speech-in-noise threshold, hearing loss and cognition from 40-69 years of age.

PubMed

Moore, David R; Edmondson-Jones, Mark; Dawes, Piers; Fortnum, Heather; McCormack, Abby; Pierzycki, Robert H; Munro, Kevin J

2014-01-01

Healthy hearing depends on sensitive ears and adequate brain processing. Essential aspects of both hearing and cognition decline with advancing age, but it is largely unknown how one influences the other. The current standard measure of hearing, the pure-tone audiogram is not very cognitively demanding and does not predict well the most important yet challenging use of hearing, listening to speech in noisy environments. We analysed data from UK Biobank that asked 40-69 year olds about their hearing, and assessed their ability on tests of speech-in-noise hearing and cognition. About half a million volunteers were recruited through NHS registers. Respondents completed 'whole-body' testing in purpose-designed, community-based test centres across the UK. Objective hearing (spoken digit recognition in noise) and cognitive (reasoning, memory, processing speed) data were analysed using logistic and multiple regression methods. Speech hearing in noise declined exponentially with age for both sexes from about 50 years, differing from previous audiogram data that showed a more linear decline from <40 years for men, and consistently less hearing loss for women. The decline in speech-in-noise hearing was especially dramatic among those with lower cognitive scores. Decreasing cognitive ability and increasing age were both independently associated with decreasing ability to hear speech-in-noise (0.70 and 0.89 dB, respectively) among the population studied. Men subjectively reported up to 60% higher rates of difficulty hearing than women. Workplace noise history associated with difficulty in both subjective hearing and objective speech hearing in noise. Leisure noise history was associated with subjective, but not with objective difficulty hearing. Older people have declining cognitive processing ability associated with reduced ability to hear speech in noise, measured by recognition of recorded spoken digits. Subjective reports of hearing difficulty generally show a higher

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

PubMed Central

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

Neuropsychological tests for predicting cognitive decline in older adults

PubMed Central

Baerresen, Kimberly M; Miller, Karen J; Hanson, Eric R; Miller, Justin S; Dye, Richelin V; Hartman, Richard E; Vermeersch, David; Small, Gary W

2015-01-01

Summary Aim To determine neuropsychological tests likely to predict cognitive decline. Methods A sample of nonconverters (n = 106) was compared with those who declined in cognitive status (n = 24). Significant univariate logistic regression prediction models were used to create multivariate logistic regression models to predict decline based on initial neuropsychological testing. Results Rey–Osterrieth Complex Figure Test (RCFT) Retention predicted conversion to mild cognitive impairment (MCI) while baseline Buschke Delay predicted conversion to Alzheimer’s disease (AD). Due to group sample size differences, additional analyses were conducted using a subsample of demographically matched nonconverters. Analyses indicated RCFT Retention predicted conversion to MCI and AD, and Buschke Delay predicted conversion to AD. Conclusion Results suggest RCFT Retention and Buschke Delay may be useful in predicting cognitive decline. PMID:26107318

Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

PubMed Central

Mander, Bryce A.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Lindquist, John R.; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P.

2014-01-01

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life. PMID:23354332

Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice

NASA Astrophysics Data System (ADS)

Xu, Zhipeng; Dong, Yuanlin; Wang, Hui; Culley, Deborah J.; Marcantonio, Edward R.; Crosby, Gregory; Tanzi, Rudolph E.; Zhang, Yiying; Xie, Zhongcong

2014-01-01

Post-operative cognitive dysfunction (POCD) is associated with increased cost of care, morbidity, and mortality. However, its pathogenesis remains largely to be determined. Specifically, it is unknown why elderly patients are more likely to develop POCD and whether POCD is dependent on general anesthesia. We therefore set out to investigate the effects of peripheral surgery on the cognition and Alzheimer-related neuropathology in mice with different ages. Abdominal surgery under local anesthesia was established in the mice. The surgery induced post-operative elevation in brain β-amyloid (Aβ) levels and cognitive impairment in the 18 month-old wild-type and 9 month-old Alzheimer's disease transgenic mice, but not the 9 month-old wild-type mice. The Aβ accumulation likely resulted from elevation of beta-site amyloid precursor protein cleaving enzyme and phosphorylated eukaryotic translation initiation factor 2α. γ-Secretase inhibitor compound E ameliorated the surgery-induced brain Aβ accumulation and cognitive impairment in the 18 month-old mice. These data suggested that the peripheral surgery was able to induce cognitive impairment independent of general anesthesia, and that the combination of peripheral surgery with aging- or Alzheimer gene mutation-associated Aβ accumulation was needed for the POCD to occur. These findings would likely promote more research to investigate the pathogenesis of POCD.

Demonstration of cognitive decline in Parkinson's disease using the Cambridge Cognitive Assessment (Revised) (CAMCOG-R).

PubMed

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.

Genetic Risk for Age-Related Cognitive Impairment Does Not Predict Cognitive Performance in Middle Age.

PubMed

Korthauer, Laura E; Awe, Elizabeth; Frahmand, Marijam; Driscoll, Ira

2018-05-26

Alzheimer's disease (AD) is characterized by memory loss and executive dysfunction, which correspond to structural changes to the medial temporal lobes (MTL) and prefrontal cortex (PFC), respectively. Given the overlap in cognitive deficits between healthy aging and the earliest stages of AD, early detection of AD remains a challenge. The goal of the present study was to study MTL- and PFC-dependent cognitive functioning in middle-aged individuals at genetic risk for AD or cognitive impairment who do not currently manifest any clinical symptoms. Participants (N = 150; aged 40-60 years) underwent genotyping of 47 single nucleotide polymorphisms (SNPs) in six genes previously associated with memory or executive functioning: APOE, SORL1, BDNF, TOMM40, KIBRA, and COMT. They completed two MTL-dependent tasks, the virtual Morris Water Task (vMWT) and transverse patterning discriminations task (TPDT), and the PFC-dependent reversal learning task. Although age was associated with poorer performance on the vMWT and TPDT within this middle-aged sample, there were no genotype-associated differences in cognitive performance. Although the vMWT and TPDT may be sensitive to age-related changes in cognition, carriers of APOE, SORL1, BDNF, TOMM40, KIBRA, and COMT risk alleles do not exhibit alteration in MTL- and PFC-dependent functioning in middle age compared to non-carriers.

Testosterone and Dihydrotestosterone Differentially Improve Cognition in Aged Female Mice

ERIC Educational Resources Information Center

Benice, Ted S.; Raber, Jacob

2009-01-01

Compared with age-matched male mice, female mice experience a more severe age-related cognitive decline (ACD). Since androgens are less abundant in aged female mice compared with aged male mice, androgen supplementation may enhance cognition in aged female mice. To test this, we assessed behavioral performance on a variety of tasks in 22- to…

Sexual Activity and Cognitive Decline in Older Adults.

PubMed

Allen, Mark S

2018-05-16

This prospective study tested whether sexual activity and emotional closeness during partnered sexual activity relate to cognitive decline (episodic memory performance) in older adulthood. In total, 6016 adults aged 50 and over (2672 men, 3344 women; M age = 66.0 ± 8.8 years) completed an episodic memory task and self-report questions related to health, sexual activity, and emotional closeness. Two years later, participants again completed the episodic memory task. After controlling for demographic and health-related lifestyle factors, more frequent sexual activity and greater emotional closeness during partnered sexual activity were associated with better memory performance. The association between sexual activity and memory performance was stronger among older participants in the sample. Memory performance worsened over 2 years, but change in memory performance was unrelated to sexual activity or emotional closeness during partnered sexual activity. These findings build on experimental research that has found sexual activity enhances episodic memory in non-human animals. Further research using longer timeframes and alternative measures of cognitive decline is recommended.

Feasibility and validity of mobile cognitive testing in the investigation of age-related cognitive decline.

PubMed

Schweitzer, Pierre; Husky, Mathilde; Allard, Michèle; Amieva, Hélène; Pérès, Karine; Foubert-Samier, Alexandra; Dartigues, Jean-François; Swendsen, Joel

2017-09-01

Mobile cognitive testing may be used to help characterize subtle deficits at the earliest stages of cognitive decline. Despite growing interest in this approach, comprehensive information concerning its feasibility and validity has been lacking in elderly samples. Over a one-week period, this study applied mobile cognitive tests of semantic memory, episodic memory and executive functioning in a cohort of 114 elderly non-demented community residents. While the study acceptance rate was moderate (66%), the majority of recruited individuals met minimal compliance thresholds and responded to an average of 82% of the repeated daily assessments. Missing data did not increase over the course of the study, but practice effects were observed for several test scores. However, even when controlling for practice effects, traditional neuropsychological tests were significantly associated with mobile cognitive test scores. In particular, the Isaacs Set Test was associated with mobile assessments of semantic memory (γ = 0.084, t = 5.598, p < 0.001), the Grober and Buschke with mobile assessments of episodic memory (γ = 0.069, t = 3.156, p < 0.01, and the Weschler symbol coding with mobile assessments of executive functioning (γ = 0.168, t = 4.562, p < 0.001). Mobile cognitive testing in the elderly may provide complementary and potentially more sensitive data relative to traditional neuropsychological assessment. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Education mitigates age-related decline in N-Acetylaspartate levels.

PubMed

Erickson, Kirk I; Leckie, Regina L; Weinstein, Andrea M; Radchenkova, Polina; Sutton, Bradley P; Prakash, Ruchika Shaurya; Voss, Michelle W; Chaddock-Heyman, Laura; McAuley, Edward; Kramer, Arthur F

2015-03-01

Greater educational attainment is associated with better neurocognitive health in older adults and is thought to reflect a measure of cognitive reserve. In vivo neuroimaging tools have begun to identify the brain systems and networks potentially responsible for reserve. We examined the relationship between education, a commonly used proxy for cognitive reserve, and N-acetylaspartate (NAA) in neurologically healthy older adults (N=135; mean age=66 years). Using single voxel MR spectroscopy, we predicted that higher levels of education would moderate an age-related decline in NAA in the frontal cortex. After controlling for the variance associated with cardiorespiratory fitness, sex, annual income, and creatine levels, there were no significant main effects of education (B=0.016, P=0.787) or age (B=-0.058, P=0.204) on NAA levels. However, consistent with our predictions, there was a significant education X age interaction such that more years of education offset an age-related decline in NAA (B=0.025, P=0.031). When examining working memory via the backwards digit span task, longer span length was associated with greater education (P<0.01) and showed a trend with greater NAA concentrations (P<0.06); however, there was no age X education interaction on digit span performance nor a significant moderated mediation effect between age, education, and NAA on digit span performance. Taken together, these results suggest that higher levels of education may attenuate an age-related reduction in neuronal viability in the frontal cortex.

Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

PubMed

Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

2018-06-01

Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.