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Sample records for accelerated cognitive decline

  1. Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging

    PubMed Central

    2014-01-01

    Background. Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. Methods. Up to 1,400 participants aged 19–94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. Results. Analyses revealed significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max demonstrated accelerated trajectories of cognitive decline over time. Conclusions. Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time. PMID:24192540

  2. Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's.

    PubMed

    Liu, Ganqiang; Boot, Brendon; Locascio, Joseph J; Jansen, Iris E; Winder-Rhodes, Sophie; Eberly, Shirley; Elbaz, Alexis; Brice, Alexis; Ravina, Bernard; van Hilten, Jacobus J; Cormier-Dequaire, Florence; Corvol, Jean-Christophe; Barker, Roger A; Heutink, Peter; Marinus, Johan; Williams-Gray, Caroline H; Scherzer, Clemens R

    2016-11-01

    We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates. A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models. Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60-6.25) and a hastened decline in Mini-Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18-8.73; p = 0.022). By contrast, the common, non-neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92-4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89-2.05) did not reach significance. Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674-685. © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

  3. Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

    PubMed Central

    Liu, Ganqiang; Boot, Brendon; Locascio, Joseph J.; Jansen, Iris E.; Winder‐Rhodes, Sophie; Eberly, Shirley; Elbaz, Alexis; Brice, Alexis; Ravina, Bernard; van Hilten, Jacobus J.; Cormier‐Dequaire, Florence; Corvol, Jean‐Christophe; Barker, Roger A.; Heutink, Peter; Marinus, Johan; Williams‐Gray, Caroline H.; Scherzer, C.; Hyman, B.T.; Ivinson, A.J.; Trisini‐Lipsanopoulos, A.; Franco, D.; Burke, K.; Sudarsky, L.R.; Hayes, M.T.; Umeh, C.C.; Growdon, J.H.; Schwarzschild, M.A.; Hung, A.Y.; Flaherty, A.W.; Wills, A.‐M.; Mejia, N.I.; Gomperts, S.N.; Khurana, V.; Selkoe, D.J.; Yi, T.; Page, K.; Liao, Z.; Barker, R.; Foltynie, T.; Williams‐Gray, C.H.; Mason, S.; Winder‐Rhodes, S.; Barker, R.; Williams‐Gray, C.H.; Breen, D.; Cummins, G.; Evans, J.; Winder‐Rhodes, S.; Corvol, J.‐C.; Brice, A.; Elbaz, A.; Mallet, A.; Vidailhet, M.; Bonnet, A.‐M.; Bonnet, C.; Grabli, D.; Hartmann, A.; Klebe, S.; Lacomblez, L.; Mangone, G.; Bourdain, F.; Brandel, J.‐P.; Derkinderen, P.; Durif, F.; Mesnage, V.; Pico, F.; Rascol, O.; Forlani, S.; Lesage, S.; Tahiri, K.; van Hilten, J.J.; Marinus, J.; Liao, Z.; Page, K.; Franco, D.; Duong, K.; Yi, T.; Trisini‐Lipsanopoulos, A.; Dong, X.; Sudarsky, L.R.; Hutten, S.J.; Amr, S.S.; Shoulson, I.; Tanner, C.M.; Lang, A.E.; Nalls, M.A.

    2016-01-01

    Objective We hypothesized that specific mutations in the β‐glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non‐neuropathic GD mutations confer intermediate progression rates. Methods A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models. Results Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60–6.25) and a hastened decline in Mini–Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18–8.73; p = 0.022). By contrast, the common, non‐neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92–4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89–2.05) did not reach significance. Interpretation Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into “high gear.” These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674–685 PMID:27717005

  4. Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology.

    PubMed

    Insel, Philip S; Mattsson, Niklas; Mackin, R Scott; Schöll, Michael; Nosheny, Rachel L; Tosun, Duygu; Donohue, Michael C; Aisen, Paul S; Jagust, William J; Weiner, Michael W

    2016-05-17

    To estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline. © 2016 American Academy of Neurology.

  5. Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

    DOE PAGES

    Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott; ...

    2016-04-15

    Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity,more » with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.« less

  6. Accelerating rates of cognitive decline and imaging markers associated with β-amyloid pathology

    SciTech Connect

    Insel, Philip S.; Mattsson, Niklas; Mackin, R. Scott; Schöll, Michael; Nosheny, Rachel L.; Tosun, Duygu; Donohue, Michael C.; Aisen, Paul S.; Jagust, William J.; Weiner, Michael W.

    2016-04-15

    Objective: Our objective is to estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate. Methods: In 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression. Results: Rates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline. Conclusions: A considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Lastly, future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.

  7. Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

    PubMed

    Schipper, Sandra; Aalbers, Marlien W; Rijkers, Kim; Lagiere, Melanie; Bogaarts, Jan G; Blokland, Arjan; Klinkenberg, Sylvia; Hoogland, Govert; Vles, Johan S H

    2016-12-01

    Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Synergistic Interactions between Aβ, Tau, and α-Synuclein: Acceleration of Neuropathology and Cognitive Decline

    PubMed Central

    Clinton, Lani K.; Blurton-Jones, Mathew; Myczek, Kristoffer; Trojanowski, John Q.

    2010-01-01

    Alzheimer's disease (AD), the most prevalent age-related neurodegenerative disorder, is characterized pathologically by the accumulation of β-amyloid (Aβ) plaques and tau-laden neurofibrillary tangles. Interestingly, up to 50% of AD cases exhibit a third prevalent neuropathology: the aggregation of α-synuclein into Lewy bodies. Importantly, the presence of Lewy body pathology in AD is associated with a more aggressive disease course and accelerated cognitive dysfunction. Thus, Aβ, tau, and α-synuclein may interact synergistically to promote the accumulation of each other. In this study, we used a genetic approach to generate a model that exhibits the combined pathologies of AD and dementia with Lewy bodies (DLB). To achieve this goal, we introduced a mutant human α-synuclein transgene into 3xTg-AD mice. As occurs in human disease, transgenic mice that develop both DLB and AD pathologies (DLB-AD mice) exhibit accelerated cognitive decline associated with a dramatic enhancement of Aβ, tau, and α-synuclein pathologies. Our findings also provide additional evidence that the accumulation of α-synuclein alone can significantly disrupt cognition. Together, our data support the notion that Aβ, tau, and α-synuclein interact in vivo to promote the aggregation and accumulation of each other and accelerate cognitive dysfunction. PMID:20505094

  9. Does Caring for a Spouse With Dementia Accelerate Cognitive Decline? Findings From the Health and Retirement Study.

    PubMed

    Dassel, Kara Bottiggi; Carr, Dawn C; Vitaliano, Peter

    2017-04-01

    The purpose of this study is to expand our recent work, which showed that spousal dementia caregivers compared to spousal nondementia caregivers experience an accelerated rate of frailty over time, by exploring cognitive health outcomes between dementia and nondementia caregivers. Using 8 biannual waves of the Health and Retirement Study data and performance on the modified Telephone Interview for Cognitive Status, we examined changes in cognitive health among surviving spousal caregivers (N = 1,255) of individuals with dementia (n = 192) and without dementia (n = 1,063), 2 waves prior and 2 waves following the death of the care recipient. Controlling for baseline health and contextual factors (e.g., frailty status, age, education), results revealed that dementia caregivers had significantly greater cognitive decline (p < .01) compared to nondementia caregivers. Relative to 2 waves prior to the death of their spouse, dementia caregivers declined by 1.77 points relative to nondementia caregivers (0.87 points) at the time their spouses' deaths were reported and 1.89 relative to the 1.18 points at the wave following these deaths, respectively. The findings from this study show that spousal caregivers of persons with dementia experience accelerated cognitive decline themselves compared to nondementia caregivers. These results, along with our previous study findings, suggest that this vulnerable group could benefit from early cognitive screening and psychosocial interventions designed to help dementia caregivers better maintain their cognitive and physical health during and following their intensive caregiving responsibilities.

  10. Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment

    PubMed Central

    Mei, Yufei; Duan, Chunli; Li, Xiaoxiao; Zhao, Yun; Cao, Fenghua; Shang, Shuai; Ding, Shumao; Yue, Xiangpei; Gao, Ge; Yang, Hui; Shen, Luxi; Feng, Xueyan; Jia, Jianping; Tong, Zhiqian; Yang, Xu

    2016-01-01

    Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m3) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations. PMID:26938543

  11. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

    PubMed

    Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

    2011-08-31

    Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

  12. Association Between Accelerated Multimorbidity and Age-Related Cognitive Decline in Older Baltimore Longitudinal Study of Aging Participants without Dementia.

    PubMed

    Fabbri, Elisa; An, Yang; Zoli, Marco; Tanaka, Toshiko; Simonsick, Eleanor M; Kitner-Triolo, Melissa H; Studenski, Stephanie A; Resnick, Susan M; Ferrucci, Luigi

    2016-05-01

    To explore the association between rate of physical health deterioration, operationalized as rising multimorbidity overtime, and longitudinal decline in cognitive function in older adults without dementia. Longitudinal (Baltimore Longitudinal Study of Aging (BLSA)). Community. BLSA participants aged 65 and older followed for an average of 3 years and free of dementia or mild cognitive impairment (MCI) at baseline and follow-up (N = 756). Standardized neurocognitive tests evaluating mental status, memory, executive function, processing speed, and verbal fluency were administered. Multimorbidity was assessed at each visit as number of diagnosed chronic diseases from a predefined list. Faster accumulation of chronic diseases was defined as upper quartile of rate of change in number of diseases over time (≥0.25 diseases/year). Faster accumulation of chronic diseases was significantly associated with greater rate of decline on the Category (P = .01) and Letter (P = .01) Fluency Tests. Similar trends were also found for the Trail-Making Test Parts A (P = .08) and B (P = .07); no association was found with rate of change in visual and verbal memory. Although further investigations are required to validate the results and fully understand the underlying mechanisms, these findings suggest that accelerated deterioration of physical health is associated with accelerated decline with aging in specific cognitive domains in older adults without dementia. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  13. Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes

    PubMed Central

    Ly, Han

    2016-01-01

    Type II diabetes increases the risk for cognitive decline via multiple traits. Amylin is a pancreatic hormone that has amyloidogenic and cytotoxic properties similar to the amyloid-β peptide. The amylin hormone is overexpressed in individuals with pre-diabetic insulin resistance or obesity leading to amylin oligomerization and deposition in pancreatic islets. Amylin oligomerization was implicated in the apoptosis of the insulin-producing β-cells. Recent studies showed that brain tissue from diabetic patients with cerebrovascular dementia or Alzheimer’s disease contains significant deposits of oligomerized amylin. It has also been reported that the brain amylin deposition reduced exploratory drive, recognition memory and vestibulomotor function in a rat model that overexpresses human amylin in the pancreas. These novel findings are reviewed here and the hypothesis that type II diabetes is linked with cognitive decline by amylin accumulation in the brain is proposed. Deciphering the impact of hyperamylinemia on the brain is critical for both etiology and treatment of dementia. PMID:26503000

  14. Accelerated postmenopausal cognitive decline is restricted to women with normal BMI: longitudinal evidence from the Betula project.

    PubMed

    Thilers, Petra P; Macdonald, Stuart W S; Nilsson, Lars-Göran; Herlitz, Agneta

    2010-05-01

    In order to determine whether cognitive performance is influenced by the menopausal transition, we tested cognitive performance at three time points, sampled women in earlier as well as later stages of the menopausal transition (40-65 years of age), and assessed the moderating influence of body mass index (BMI) on rate of change. Multilevel analyses were used to model change in cognitive performance as a function of number of years post menopause over and above chronological age. We investigated change in the menopausal transition for 10 cognitive outcomes in 193 women who were postmenopausal during the last test wave. The model, controlling for age and education, showed that postmenopausal women within the normal range of BMI (BMI 18.5-25) displayed more rapid decline than women with BMI above 25 for measures of visuospatial ability and episodic memory. In addition, there was an accelerated rate of change post menopause for all women on verbal fluency. The results support the notion that the diminished postmenopausal production of endogenous estrogen may have a slight negative influence on cognitive abilities, but mainly for women within a normal BMI range.

  15. Cognitive decline in Parkinson disease.

    PubMed

    Aarsland, Dag; Creese, Byron; Politis, Marios; Chaudhuri, K Ray; Ffytche, Dominic H; Weintraub, Daniel; Ballard, Clive

    2017-04-01

    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.

  16. Accelerated protein damage in brains of PIMT+/- mice; a possible model for the variability of cognitive decline in human aging.

    PubMed

    Qin, Zhenxia; Dimitrijevic, Aleksandra; Aswad, Dana W

    2015-02-01

    Isoaspartate formation is a common type of protein damage normally kept in check by the repair enzyme protein-L-isoaspartyl methyltransferase (PIMT). Mice with a knockout of the gene (Pcmt1) for this enzyme (KO, -/-) exhibit a pronounced neuropathology with fatal epileptic seizures at 30-60 days. Heterozygous (HZ, +/-) mice have 50% of the PIMT activity found in wild-type (WT, +/+) mice, but appear normal. To see if HZ mice exhibit accelerated aging at the molecular level, we compared brain extracts from HZ and WT mice at 8 months and 2 years with regard to PIMT activity, isoaspartate levels, and activity of an endogenous PIMT substrate, creatine kinase B. PIMT activity declined modestly with age in both genotypes. Isoaspartate was significantly higher in HZ than WT mice at 8 months and more so at 2 years, rising 5× faster in HZ males and 3× faster in females. Creatine kinase activity decreased with age and was always lower in the HZ mice. These findings suggest the individual variation of human PIMT levels may significantly influence the course of age-related central nervous system dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. 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.

  18. Intracerebral haemorrhage and cognitive decline.

    PubMed

    Murao, K; Rossi, C; Cordonnier, C

    2013-10-01

    Relationships between intracerebral hemorrhage (ICH) and dementia might be of interest since some causes of ICH such as cerebral amyloid angiopathy are strongly linked with dementia, especially Alzheimer's disease. The aim of this narrative review was to highlight the interesting relationship of ICH lesions and cognitive decline leading to dementia. We considered the whole spectrum of hemorrhagic lesions in the brain parenchyma, namely spontaneous ICH and brain microbleeds. Copyright © 2013. Published by Elsevier Masson SAS.

  19. Association of gene variants of the renin-angiotensin system with accelerated hippocampal volume loss and cognitive decline in old age.

    PubMed

    Zannas, Anthony S; McQuoid, Douglas R; Payne, Martha E; MacFall, James R; Ashley-Koch, Allison; Steffens, David C; Potter, Guy G; Taylor, Warren D

    2014-11-01

    Genetic factors confer risk for neuropsychiatric phenotypes, but the polygenic etiology of these phenotypes makes identification of genetic culprits challenging. An approach to this challenge is to examine the effects of genetic variation on relevant endophenotypes, such as hippocampal volume loss. A smaller hippocampus is associated with gene variants of the renin-angiotensin system (RAS), a system implicated in vascular disease. However, no studies to date have investigated longitudinally the effects of genetic variation of RAS on the hippocampus. The authors examined the effects of polymorphisms of AGTR1, the gene encoding angiotensin-II type 1 receptor of RAS, on longitudinal hippocampal volumes of older adults. In all, 138 older adults (age ≥60 years) were followed for an average of about 4 years. The participants underwent repeated structural MRI and comprehensive neurocognitive testing, and they were genotyped for four AGTR1 single-nucleotide polymorphisms (SNPs) with low pairwise linkage disequilibrium values and apolipoprotein E (APOE) genotype. Genetic variants at three AGTR1 SNPs (rs2638363, rs1492103, and rs2675511) were independently associated with accelerated hippocampal volume loss over the 4-year follow-up period in the right but not left hemisphere. Intriguingly, these AGTR1 risk alleles also predicted worse episodic memory performance but were not related to other cognitive measures. Two risk variants (rs2638363 and rs12721331) interacted with the APOE4 allele to accelerate right hippocampal volume loss. Risk genetic variants of the RAS may accelerate memory decline in older adults, an effect that may be conferred by accelerated hippocampal volume loss. Molecules involved in this system may hold promise as early therapeutic targets for late-life neuropsychiatric disorders.

  20. Gene variants of the renin-angiotensin system are associated with accelerated hippocampal volume loss and cognitive decline in old age

    PubMed Central

    Zannas, Anthony S.; McQuoid, Douglas R.; Payne, Martha E; MacFall, James R.; Ashley-Koch, Allison; Steffens, David C.; Potter, Guy G.; Taylor, Warren D.

    2014-01-01

    Objective Genetic factors confer risk for neuropsychiatric phenotypes, but the polygenic etiology of these phenotypes makes identification of genetic culprits challenging. An approach to this challenge is to examine the effects of genetic variation on relevant endophenotypes, such as hippocampal volume loss. Smaller hippocampus is associated with gene variants of the renin-angiotensin system (RAS), a system implicated in vascular disease. However, no studies have investigated longitudinally the effects of genetic variation of RAS on the hippocampus. Method We examined the effects of polymorphisms of AGTR1, the gene encoding angiotensin-II type 1 receptor of RAS, on longitudinal hippocampal volumes of older adults. 138 older adults (age ≥ 60 years) were followed for an average of about four years. Subjects underwent repeated structural MRI and comprehensive neurocognitive testing, and were genotyped for four AGTR1 SNPs with low pairwise linkage disequilibrium values and apolipoprotein E (APOE) genotype. Results Genetic variants at three AGTR1 SNPs (rs2638363, rs1492103, rs2675511) were independently associated with accelerated hippocampal volume loss over the four-year follow-up in the right but not left hemisphere. Intriguingly, these AGTR1 risk alleles also predicted worse episodic memory performance but were not related to other cognitive measures. Two risk variants (rs2638363 and rs12721331) interacted with the APOE4 allele to accelerate right hippocampal volume loss. Conclusions Risk genetic variants of RAS may accelerate memory decline in older adults, an effect that may be conferred by accelerated hippocampal volume loss. Molecules involved in this system may hold promise as early therapeutic targets for late-life neuropsychiatric disorders. PMID:25124854

  1. Dietary Factors and Cognitive Decline.

    PubMed

    Smith, P J; Blumenthal, J A

    2016-03-01

    Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing 'whole' diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed.

  2. Dietary Factors and Cognitive Decline

    PubMed Central

    Smith, P.J.; Blumenthal, J.A.

    2015-01-01

    Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing ‘whole’ diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed. PMID:26900574

  3. Senescence-accelerated OXYS rats: a model of age-related cognitive decline with relevance to abnormalities in Alzheimer disease.

    PubMed

    Stefanova, Natalia A; Kozhevnikova, Oyuna S; Vitovtov, Anton O; Maksimova, Kseniya Yi; Logvinov, Sergey V; Rudnitskaya, Ekaterina A; Korbolina, Elena E; Muraleva, Natalia A; Kolosova, Nataliya G

    2014-01-01

    Senescence-accelerated OXYS rats are an experimental model of accelerated aging that was established from Wistar stock via selection for susceptibility to cataractogenic effects of a galactose-rich diet and via subsequent inbreeding of highly susceptible rats. Currently, we have the 102nd generation of OXYS rats with spontaneously developing cataract and accelerated senescence syndrome, which means early development of a phenotype similar to human geriatric disorders, including accelerated brain aging. In recent years, our group found strong evidence that OXYS rats are a promising model for studies of the mechanisms of brain aging and neurodegenerative processes similar to those seen in Alzheimer disease (AD). The manifestation of behavioral alterations and learning and memory deficits develop since the fourth week of age, i.e., simultaneously with first signs of neurodegeneration detectable on magnetic resonance imaging and under a light microscope. In addition, impaired long-term potentiation has been demonstrated in OXYS rats by the age of 3 months. With age, neurodegenerative changes in the brain of OXYS rats become amplified. We have shown that this deterioration happens against the background of overproduction of amyloid precursor protein (AβPP), accumulation of β-amyloid (Aβ), and hyperphosphorylation of the tau protein in the hippocampus and cortex. The development of AMD-like retinopathy in OXYS rats is also accompanied by increased accumulation of Aβ in the retina. These published data suggest that the OXYS strain may serve as a spontaneous rat model of AD-like pathology and could help to decipher the pathogenesis of AD.

  4. Early Onset of Diabetes Mellitus Accelerates Cognitive Decline in Japanese Patients with Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episodes.

    PubMed

    Murakami, Takaaki; Shinoto, Yuya; Yonemitsu, Shin; Muro, Seiji; Oki, Shogo; Koga, Yasutoshi; Goto, Yu-Ichi; Kaneda, Daita

    2016-04-01

    Approximately 80% of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) carry the A3243G mutation in the mitochondrial tRNALeu (UUR) gene. Conversely, this mutation has also been identified as one of the most prevalent genetic abnormalities in patients with diabetes mellitus. Mitochondrial diabetes mellitus complicated with MELAS is relatively common, and 12.5% of patients with the A3243G mutation develop MELAS after being diagnosed with diabetes mellitus. However, the clinical impact of diabetes mellitus in MELAS patients remains unclear. Therefore, we retrospectively studied 14 Japanese MELAS patients with the A3243G mutation: three men and eleven women, with the mean age of 48.0 (± 15.4) years. Eight patients had been diagnosed with diabetes mellitus prior to the diagnosis of mitochondrial disease, and all of them were treated with insulin. The other six included four patients with concurrent diagnosis of diabetes and mitochondrial disease, one patient diagnosed with diabetes after the diagnosis of mitochondrial disease, and one patient without developing diabetes currently. We thus compared the patients' characteristics between those with and without early onset of diabetes mellitus. Cognitive decline (75.0% vs. 0%; p = 0.03) and poor glycemic control with severe hypoglycemic events (75.0% vs. 16.7%; p = 0.05) were more common in MELAS patients with a prior diagnosis of diabetes than in those without the prior diagnosis of diabetes. Our data suggest that the latent progress of cognitive decline is accelerated because of early onset of diabetes mellitus in MELAS patients.

  5. The relationship between obesity and cognitive health and decline.

    PubMed

    Dye, Louise; Boyle, Neil Bernard; Champ, Claire; Lawton, Clare

    2017-09-11

    The relationship between obesity and cognitive impairment is important given the globally ageing population in whom cognitive decline and neurodegenerative disorders will carry grave individual, societal and financial burdens. This review examines the evidence for the link between obesity and cognitive function in terms of both the immediate effects on cognitive performance, and effects on the trajectory of cognitive ageing and likelihood of dementia. In mid-life, there is a strong association between obesity and impaired cognitive function. Anthropometric measures of obesity are also associated with reduced neural integrity (e.g. grey and white matter atrophy). Increasing age coupled with the negative metabolic consequences of obesity (e.g. type 2 diabetes mellitus) are likely to significantly contribute to cognitive decline and incidence of dementia. Stress is identified as a potential risk factor promoting abdominal obesity and contributing to impaired cognitive function. However, the potentially protective effects of obesity against cognitive decline in older age require further examination. Finally, surgical and whole diet interventions, which address obesity may improve cognitive capacity and confer some protection against later cognitive decline. In conclusion, obesity and its comorbidities are associated with impaired cognitive performance, accelerated cognitive decline and neurodegenerative pathologies such as dementia in later life. Interventions targeting mid-life obesity may prove beneficial in reducing the cognitive risks associated with obesity.

  6. Trajectory of Cognitive Decline after Incident Stroke

    PubMed Central

    Levine, Deborah A.; Galecki, Andrzej T.; Langa, Kenneth M.; Unverzagt, Frederick W.; Kabeto, Mohammed U.; Giordani, Bruno; Wadley, Virginia G.

    2015-01-01

    .097); however, there was a significantly faster poststroke rate of incident cognitive impairment compared to the prestroke rate (odds ratio, 1.23 per year; 95% CI, 1.10–1.38; P<0.001). For a 70 year-old black woman, stroke at year 3 was associated with greater incident cognitive impairment: absolute difference (95% CI) of 4.0% (−1.2%–9.2%) at year 3 and 12.4% (7.7%–17.1% at year 6). Conclusion Incident stroke was associated with an acute decline in cognition and also accelerated and persistent cognitive decline over 6 years. PMID:26151265

  7. 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

  8. Cognitive decline and the default American lifestyle.

    PubMed

    Mirowsky, John

    2011-07-01

    Upward trends in IQ, education, and mental work suggest that cognitive function among seniors should be rising strongly across cohorts. There is little sign of such improvement in recent decades, and some analyses find poorer function in the newer cohorts. This essay explores possible explanations of the anomaly. Major long-term trends that might increase cognitive impairment are reviewed, and their implications are considered. Physical activity is declining, food is increasingly manufactured, body fat is increasing, diabetes and metabolic syndrome are on the rise, the number of prescription drugs per person is increasing, and the proportion of the population either old or obese is growing. Technological and economic development may lower the cognitive function needed for survival. They also lower physical activity in daily life. Sedentary work, transportation, and leisure undermine the aerobic and metabolic fitness required for the brain to perform well. Some prescription drugs impair cognitive function, and others do so when taken for many years or in combination with others. The growing fraction of the population that is either old or obese may further lower physical activity norms and requirements and substitute medical intervention for health, accelerating a trend toward cognitive impairment.

  9. Cognitive Decline and the Default American Lifestyle

    PubMed Central

    2011-01-01

    Objectives. Upward trends in IQ, education, and mental work suggest that cognitive function among seniors should be rising strongly across cohorts. There is little sign of such improvement in recent decades, and some analyses find poorer function in the newer cohorts. This essay explores possible explanations of the anomaly. Methods. Major long-term trends that might increase cognitive impairment are reviewed, and their implications are considered. Results. Physical activity is declining, food is increasingly manufactured, body fat is increasing, diabetes and metabolic syndrome are on the rise, the number of prescription drugs per person is increasing, and the proportion of the population either old or obese is growing. Discussion. Technological and economic development may lower the cognitive function needed for survival. They also lower physical activity in daily life. Sedentary work, transportation, and leisure undermine the aerobic and metabolic fitness required for the brain to perform well. Some prescription drugs impair cognitive function, and others do so when taken for many years or in combination with others. The growing fraction of the population that is either old or obese may further lower physical activity norms and requirements and substitute medical intervention for health, accelerating a trend toward cognitive impairment. PMID:21743052

  10. Cognitive Issues: Decline, Delirium, Depression, Dementia.

    PubMed

    Harris, Melodee

    2017-09-01

    Cognitive decline in older persons can be pathologic or occur as a part of the normal aging process. Delirium, depression, and dementia are geriatric syndromes and neurocognitive disorders that are the result of cognitive decline associated with pathology. This overview is a brief guide on cognitive decline and how to identify, manage, and treat associated neurocognitive disorders, including delirium, depression, and dementia. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Biomarkers of cognitive decline in Parkinson's disease.

    PubMed

    Lin, Chin-Hsien; Wu, Ruey-Meei

    2015-05-01

    Cognitive impairment is a frequent and devastating non-motor symptom of Parkinson's disease (PD). Impaired cognition has a major impact on either quality of life or mortality in patients with PD. Notably, the rate of cognitive decline and pattern of early cognitive deficits in PD are highly variable between individuals. Given that the underlying mechanisms of cognitive decline or dementia associated with PD remain unclear, there is currently no mechanism-based treatment available. Identification of biological markers, including neuroimaging, biofluids and common genetic variants, that account for the heterogeneity of PD related cognitive decline could provide important insights into the pathological processes that underlie cognitive impairment in PD. These combined biomarker approaches will enable early diagnosis and provide indicators of cognitive progression in PD patients. This review summarizes recent advances in the development of biomarkers for cognitive impairments in PD.

  12. Cognitive deterioration in adult epilepsy: Does accelerated cognitive ageing exist?

    PubMed

    Breuer, L E M; Boon, P; Bergmans, J W M; Mess, W H; Besseling, R M H; de Louw, A; Tijhuis, A G; Zinger, S; Bernas, A; Klooster, D C W; Aldenkamp, A P

    2016-05-01

    A long-standing concern has been whether epilepsy contributes to cognitive decline or so-called 'epileptic dementia'. Although global cognitive decline is generally reported in the context of chronic refractory epilepsy, it is largely unknown what percentage of patients is at risk for decline. This review is focused on the identification of risk factors and characterization of aberrant cognitive trajectories in epilepsy. Evidence is found that the cognitive trajectory of patients with epilepsy over time differs from processes of cognitive ageing in healthy people, especially in adulthood-onset epilepsy. Cognitive deterioration in these patients seems to develop in a 'second hit model' and occurs when epilepsy hits on a brain that is already vulnerable or vice versa when comorbid problems develop in a person with epilepsy. Processes of ageing may be accelerated due to loss of brain plasticity and cognitive reserve capacity for which we coin the term 'accelerated cognitive ageing'. We believe that the concept of accelerated cognitive ageing can be helpful in providing a framework understanding global cognitive deterioration in epilepsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Atrial Fibrillation, Cognitive Decline And Dementia

    PubMed Central

    Alonso, Alvaro; Arenas de Larriva, Antonio P.

    2016-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia. Growing evidence supports a role for AF as a risk factor for cognitive decline and dementia. In this review, we summarize epidemiologic observations linking AF with cognitive outcomes, describe potential mechanisms, and explore the impact of AF treatments on cognitive decline and dementia. Community-based, observational studies show a consistent higher rate of cognitive decline and risk of dementia in persons with AF. These associations are partly due to the increased risk of clinical stroke in AF, but other mechanisms, including incidence of silent cerebral infarcts, microbleeds, and cerebral hypoperfusion, are likely additional contributors. Adequate oral anticoagulation and improved management of the overall cardiovascular risk profile in persons with AF offer the promise of reducing the impact of AF on cognitive decline and dementia. PMID:27547248

  14. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    PubMed

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation.

  15. Cholesterol and late-life cognitive decline.

    PubMed

    van Vliet, Peter

    2012-01-01

    High cholesterol levels are a major risk factor for cardiovascular disease, but their role in dementia and cognitive decline is less clear. This review highlights current knowledge on the role of cholesterol in late-life cognitive function, cognitive decline, and dementia. When measured in midlife, high cholesterol levels associate with an increased risk of late-life dementia and cognitive decline. However, when measured in late-life, high cholesterol levels show no association with cognitive function, or even show an inverse relation. Although statin treatment has been shown to associate with a lower risk of dementia and cognitive decline in observational studies, randomized controlled trials show no beneficial effect of statin treatment on late-life cognitive function. Lowering cholesterol levels may impair brain function, since cholesterol is essential for synapse formation and maturation and plays an important role in the regulation of signal transduction through its function as a component of the cell membrane. However, membrane cholesterol also plays a role in the formation and aggregation of amyloid-β. Factors that influence cholesterol metabolism, such as dietary intake, are shown to play a role in late-life cognitive function and the risk of dementia. In conclusion, cholesterol associates with late-life cognitive function, but the association is strongly age-dependent. There is no evidence that treatment with statins in late-life has a beneficial effect on cognitive function.

  16. Can exercise prevent cognitive decline?

    PubMed

    Behrman, Sophie; Ebmeier, Klaus P

    2014-01-01

    As the tolerability of pharmacological agents decreases with age, exercise may be particularly helpful as a possible treatment or stabiliser of mood and cognitive function in older age. Exercise has been most commonly evaluated for the treatment of depression. Exercise interventions designed primarily for treatment of physical conditions in the elderly do appear to confer psychological benefits as well, with reduction in depressive symptoms over the course of treatment. The effects of exercise on reducing depressive symptoms are not dissimilar to the effects of antidepressant drugs and cognitive behaviour therapy. Exercise may be a useful low-tech intervention for people with mild to moderate depression. In particular, exercise may be helpful in the elderly and in patients who have had insufficient response to, or are intolerant of, pharmacotherapy. Mastery of a new skill and positive feedback from others may increase feelings of self-esteem and improve mood. Exercise may distract participants from persistent negative thoughts. Exercise has been shown to improve executive function acutely in adults of all ages. It is possible that dance routines or other exercise regimens requiring some cognitive input may confer additional benefit to cognitive function. Exercise has a moderate effect on the ability of people with dementia to perform activities of daily living and may improve cognitive function. Midlife exercise may also have an impact on later cognitive function.

  17. Rapid cognitive decline in Alzheimer's disease. Consensus paper.

    PubMed

    Soto, M E; Andrieu, S; Arbus, C; Ceccaldi, M; Couratier, P; Dantoine, T; Dartigues, J-F; Gillette-Guyonnet, S; Nourhashemi, F; Ousset, P-J; Poncet, M; Portet, F; Touchon, J; Vellas, B

    2008-12-01

    The rate of cognitive decline in Alzheimer's disease (AD) varies considerably between individuals, with some subjects showing substantial deterioration and others showing little or no change over the course of the disease. These wide variations support the relatively new concept of Rapid Cognitive Decline (RCD). Patients with an accelerated rate of cognitive decline have showed to present a worse evolution in terms of mortality, loss of autonomy and institutionalisation. The conclusions from RCD studies conducted in the past years remain very heterogeneous and sometimes contradictory. This is possibly due to methodological differences, mainly the different "a priori" definitions of RCD used to identify rapid decliners. Consequently of this, there is considerable variation in reported frequency of patients with RCD which may vary from 9.5% to 54%. The lack of both consensus definition and consensual clinical assessment tools is one of the major barriers for establishing an appropriated management of rapid decliners in clinical practice. Presently, management of rapid decliners in AD remains to be a challenge waiting to better know predictive factors of a RCD. To date no specific guidelines exist to follow-up or to treat patients with this condition. This consensus paper proposes the loss of 3 points or greater in Mini-Mental State Examination (MMSE) during six months as an empirical definition of rapid cognitive decline to be used in routine medical practice and to be relevant for clinical-decision making in patients with mild to moderately-severe AD.

  18. The impact of retirement on age related cognitive decline - a systematic review.

    PubMed

    Meng, Annette; Nexø, Mette Andersen; Borg, Vilhelm

    2017-07-21

    Knowledge on factors affecting the rate of cognitive decline and how to maintain cognitive functioning in old age becomes increasingly relevant. The purpose of the current study was to systematically review the evidence for the impact of retirement on cognitive functioning and on age related cognitive decline. We conducted a systematic literature review, following the principles of the PRISMA statement, of longitudinal studies on the association between retirement and cognition. Only seven studies fulfilled the inclusion criteria. We found weak evidence that retirement accelerates the rate of cognitive decline in crystallised abilities, but only for individuals retiring from jobs high in complexity with people. The evidence of the impact of retirement on the rate of decline in fluid cognitive abilities is conflicting. The review revealed a major knowledge gap in regards to the impact of retirement on cognitive decline. More knowledge on the association between retirement and age related cognitive decline as well as knowledge on the mechanisms behind these associations is needed.

  19. MIND diet slows cognitive decline with aging.

    PubMed

    Morris, Martha Clare; Tangney, Christy C; Wang, Yamin; Sacks, Frank M; Barnes, Lisa L; Bennett, David A; Aggarwal, Neelum T

    2015-09-01

    The Mediterranean and dash diets have been shown to slow cognitive decline; however, neither diet is specific to the nutrition literature on dementia prevention. We devised the Mediterranean-Dietary Approach to Systolic Hypertension (DASH) diet intervention for neurodegenerative delay (MIND) diet score that specifically captures dietary components shown to be neuroprotective and related it to change in cognition over an average 4.7 years among 960 participants of the Memory and Aging Project. In adjusted mixed models, the MIND score was positively associated with slower decline in global cognitive score (β = 0.0092; P < .0001) and with each of five cognitive domains. The difference in decline rates for being in the top tertile of MIND diet scores versus the lowest was equivalent to being 7.5 years younger in age. The study findings suggest that the MIND diet substantially slows cognitive decline with age. Replication of these findings in a dietary intervention trial would be required to verify its relevance to brain health. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  20. Nutritional factors, cognitive decline, and dementia.

    PubMed

    Del Parigi, Angelo; Panza, Francesco; Capurso, Cristiano; Solfrizzi, Vincenzo

    2006-03-15

    Nutritional factors and nutritional deficiencies have been repeatedly associated with cognitive impairment. Most of the evidence is based on cross-sectional studies, which cannot prove whether a nutritional deficit is the cause or the consequence of an impaired cognitive status. In fact, cognitive impairment, in turn, can determine changes in dietary habits and consequent nutritional deficiencies. We reviewed clinical and epidemiological studies from January 1983 to June 2004. Several cross-sectional and fewer prospective studies reported an association between dietary or supplemental intake of antioxidants and protection from cognitive decline and dementia. There are negative reports as well and some methodological biases might have affected the consistencies across studies. Deficiencies of several B vitamins have been associated with cognitive dysfunction in many observational studies. More recently, deficiencies of folate (B9) and cobalamine (B12) have been studied in relation to hyperhomocysteinemia as potential determinants of cognitive impairment, dementia, and Alzheimer's disease (AD). A small number of studies assessed the association between intake of macronutrients and cognitive function or dementia. Among the others, the intake of fatty acids and cholesterol has received particular attention. Although the results are not always consistent, most studies have reported a protective role of dietary intakes of poly- and mono-unsaturated fatty acids against cognitive decline and AD. We point out that well designed intervention studies are warranted in order to establish specific levels of micro- and macronutrient deficiencies and to set general recommendations for the population.

  1. 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

  2. Cognitive decline and the neighborhood environment.

    PubMed

    Clarke, Philippa J; Weuve, Jennifer; Barnes, Lisa; Evans, Denis A; Mendes de Leon, Carlos F

    2015-11-01

    Little research has looked beyond individual factors to consider the influence of the neighborhood environment on cognitive function. A greater density of physical resources (e.g., recreational centers and parks) and institutional resources (e.g., community centers) may buffer cognitive decline by offering opportunities for physical activity and social interaction. Using data from the Chicago Health and Aging Project (1993-2011), a prospective cohort study of 6518 adults of age 65 years or older, we fit a three-level growth curve model to examine the role of individual and neighborhood factors (objectively observed at the block group level) on trajectories of cognitive function (composite of East Boston Memory Test, symbol digit test, and Mini Mental State Examination) in later life. Net of individual factors, residence in a neighborhood with community resources, proximity to public transit, and public spaces in good condition were associated with slower rates of cognitive decline, possibly by increasing opportunities for social and physical activities or access to destinations that facilitate engagement in activities. These results highlight the role of neighborhood environments in buffering cognitive decline among older adults aging in place. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Cognitive Decline and the Neighborhood Environment

    PubMed Central

    Clarke, Philippa J.; Weuve, Jennifer; Barnes, Lisa; Evans, Denis A.; Mendes de Leon, Carlos F.

    2015-01-01

    Purpose Little research has looked beyond individual factors to consider the influence of the neighborhood environment on cognitive function. A greater density of physical resources (e.g., recreational centers and parks) and institutional resources (e.g., community centers) may buffer cognitive decline by offering opportunities for physical activity and social interaction. Methods Using data from the Chicago Health and Aging Project (1993–2011), a prospective cohort study of 6518 adults age 65+, we fit a 3-level growth curve model to examine the role of individual and neighborhood factors (objectively observed at the block group level) on trajectories of cognitive function (composite of East Boston Memory Test, symbol digit test, MMSE) in later life. Results Net of individual factors, residence in a neighborhood with community resources, proximity to public transit, and public spaces in good condition were associated with slower rates of cognitive decline, possibly by increasing opportunities for social and physical activities or access to destinations that facilitate engagement in activities. Conclusions These results highlight the role of neighborhood environments in buffering cognitive decline among older adults aging in place. PMID:26253697

  4. Antihypertensive treatments, cognitive decline, and dementia.

    PubMed

    Duron, Emmanuelle; Hanon, Olivier

    2010-01-01

    Chronic hypertension is associated with an increased risk of both vascular dementia and Alzheimer's disease (AD). In this context, the role of anti-hypertensive therapy for the prevention and delay of cognitive decline and dementia is of central importance. Most longitudinal studies have shown a significant inverse association between anti-hypertensive therapies and dementia incidence and for some of these, particularly in AD. Seven randomized, double blind placebo-controlled trials have evaluated the benefit of antihypertensive treatments on cognition. Three of them found positive results in term of prevention of dementia (SYST-EUR) or cognitive decline (PROGRESS, HOPE). Others disclosed non-significant results (MRC, SHEP, SCOPE, HYVET-COG). This discrepancy emphasizes the difficulty to perform such trials: the follow-up has to be long enough to disclose a benefit, a large number of patients is needed for these studies, and because of ethical reasons some anti-hypertensive treatments are often prescribed in the placebo group. Results of the two more recent meta-analyses are inconsistent, possibly due to methodological issues. Antihypertensive treatments could be beneficial to cognitive function by lowering blood pressure and/or by specific neuroprotective effect. Three main antihypertensive subclasses have been associated with a beneficial effect on cognitive function beyond blood pressure reduction (calcium channel blockers, angiotensin converting enzyme inhibitor, angiotensin-AT1-receptor-blockers). Further long-term randomized trials, designed especially to assess a link between antihypertensive therapy and cognitive decline or dementia are therefore needed with cognition as the primary outcome. A low blood pressure threshold that could be deleterious for cognitive function should also be determined.

  5. The neuroinflammatory response of postoperative cognitive decline

    PubMed Central

    Vacas, Susana; Degos, Vincent; Feng, Xiaomei; Maze, Mervyn

    2013-01-01

    Background Aseptic surgical trauma provokes a homeostatic neuroinflammatory response to promote healing and protect the organism from further injury. When this response is dysregulated, harmful consequences can follow, including postoperative cognitive decline. Sources of data We performed a comprehensive search on PubMed related to postoperative cognitive dysfunction (POCD). Areas of agreement Although the precise pathogenic mechanisms for POCD remain unclear, certain risk factors are known. Areas of controversy The mechanisms that lead to exaggerated and persistent neuroinflammation and the best way to counteract it are still unknown. Areas for developing research It is imperative that we identify the underlying processes that increase the risk of cognitive decline in elderly surgical patients. In this review we explore non-resolution of inflammation as an underlying cause of developing exaggerated and persistent POCD. If interventions can be developed to promote resolution of neuroinflammation, the patient's postoperative recovery will be enhanced and long-term consequences can be prevented. PMID:23558082

  6. Detection and Prevention of Cognitive Decline.

    PubMed

    Small, Gary W

    2016-12-01

    Current diagnostic and treatment strategies for cognitive decline can help patients maintain cognitive ability and higher levels of function longer. Despite advances in detection and early treatment strategies, many patients do not receive proper assessments and available therapies. A systematic assessment strategy will increase the likelihood of an accurate diagnosis, which can facilitate pharmacologic and non-pharmacologic treatment plans that can have a meaningful impact on prognosis. Available data support the integration of healthy lifestyle strategies in the treatment plan to help to stabilize symptoms and potentially delay future cognitive decline. While investigators continue to pursue more effective detection, treatment, and prevention strategies, the scientific data support the use of symptomatic drug treatments and recommendations for healthy lifestyle behaviors to improve quality of life and potentially stave off future cognitive decline. Success of such healthy lifestyle programs involves educating participants on the connection between lifestyle and disease prevention, offering enjoyable exercises that target the patient's skill level, and providing feedback that motivates participants to continue their healthy behaviors so they become habits.

  7. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  8. Inappropriate treatments for patients with cognitive decline.

    PubMed

    Robles Bayón, A; Gude Sampedro, F

    2014-01-01

    Some treatments are inappropriate for patients with cognitive decline. We analyse their use in 500 patients and present a literature review. Benzodiazepines produce dependence, and reduce attention, memory, and motor ability. They can cause disinhibition or aggressive behaviour, facilitate the appearance of delirium, and increase accident and mortality rates in people older than 60. In subjects over 65, low systolic blood pressure is associated with cognitive decline. Maintaining this figure between 130 and 140 mm Hg (145 in patients older than 80) is recommended. Hypocholesterolaemia < 160 mg/dl is associated with increased morbidity and mortality, aggressiveness, and suicide; HDL-cholesterol<40 mg/dl is associated with memory loss and increased vascular and mortality risks. Old age is a predisposing factor for developing cognitive disorders or delirium when taking opioids. The risks of prescribing anticholinesterases and memantine to patients with non-Alzheimer dementia that is not associated with Parkinson disease, mild cognitive impairment, or psychiatric disorders probably outweigh the benefits. Anticholinergic drugs acting preferentially on the peripheral system can also induce cognitive side effects. Practitioners should be aware of steroid-induced dementia and steroid-induced psychosis, and know that risk of delirium increases with polypharmacy. Of 500 patients with cognitive impairment, 70.4% were on multiple medications and 42% were taking benzodiazepines. Both conditions were present in 74.3% of all suspected iatrogenic cases. Polypharmacy should be avoided, if it is not essential, especially in elderly patients and those with cognitive impairment. Benzodiazepines, opioids and anticholinergics often elicit cognitive and behavioural disorders. Moreover, systolic blood pressure must be kept above 130 mm Hg, total cholesterol levels over 160 mg/dl, and HDL-cholesterol over 40 mg/dl in this population. Copyright © 2012 Sociedad Española de Neurolog

  9. Delirium is a risk factor for further cognitive decline in cognitively impaired hip fracture patients.

    PubMed

    Krogseth, Maria; Watne, Leiv Otto; Juliebø, Vibeke; Skovlund, Eva; Engedal, Knut; Frihagen, Frede; Wyller, Torgeir Bruun

    2016-01-01

    Delirium is a risk factor for dementia in cognitively intact patients. Whether an episode of delirium accelerates cognitive decline in patients with known dementia, is less explored. This is a prospective follow-up study of 287 hip fracture patients with pre-fracture cognitive impairment. During the hospitalization, the patients were screened daily for delirium using the Confusion Assessment Method. Pre-fracture cognitive impairment was defined as a score of 3.44 or higher on the pre-fracture Informant Questionnaire on Cognitive Decline in the Elderly Short Form (IQCODE-SF). At follow-up after 4-6 months, the caregivers rated cognitive changes emerging after the fracture using the IQCODE-SF, and the patients were tested with the Mini Mental State Examination (MMSE). A sub-group of the patients had a pre-fracture MMSE score which was used to calculate the yearly decline on the MMSE in patients with and without delirium. 201 of the 287 patients developed delirium in the acute phase. In linear regression analysis, delirium was a significant and independent predictor of a more prominent cognitive decline at follow-up measured by the IQCODE-SF questionnaire (p=0.002). Among patients having a pre-fracture MMSE score, the patients developing delirium had a median (IQR) yearly decline of 2.4 points (1.1-3.9), compared to 1.0 points (0-1.9) in the group without delirium (p=0.001, Mann-Whitney test). Hip fracture patients with pre-fracture dementia run a higher risk of developing delirium. Delirium superimposed on dementia is a significant predictor of an accelerated further cognitive decline. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Dehydroepiandrosterone and age-related cognitive decline.

    PubMed

    Sorwell, Krystina G; Urbanski, Henryk F

    2010-03-01

    In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.

  11. Educational inequalities in aging-related declines in fluid cognition and the onset of cognitive pathology.

    PubMed

    Clouston, Sean A P; Glymour, Maria; Terrera, Graciela Muñiz

    2015-09-01

    Education has been robustly associated with cognitive reserve and dementia, but not with the rate of cognitive aging, resulting in some confusion about the mechanisms of cognitive aging. This study uses longitudinal data to differentiate between trajectories indicative of healthy versus pathological cognitive aging. Participants included 9,401 Health and Retirement Study respondents aged 55 and older who completed cognitive testing regularly over 17.3 years until most recently in 2012. Individual-specific random change-point modeling was used to identify age of incident pathological decline; acceleration is interpreted as indicating likely onset of pathological decline when it is significant and negative. These methods detect incident dementia diagnoses with specificity/sensitivity of 89.3%/44.3%, 5.6 years prior to diagnosis. Each year of education was associated with 0.09 (95% CI, 0.087-0.096; P<0.001) standard deviation higher baseline cognition and delayed onset of cognitive pathology (HR, 0.98; 95% CI, 0.96-0.99; P=0.006). Longitudinal random change-point modeling was able to reliably identify incident dementia. Accounting for incident cognitive pathology, we find that education predicts cognitive capability and delayed onset pathological declines.

  12. Perspectives on depression, mild cognitive impairment, and cognitive decline.

    PubMed

    Steffens, David C; Otey, Emeline; Alexopoulos, George S; Butters, Meryl A; Cuthbert, Bruce; Ganguli, Mary; Geda, Yonas E; Hendrie, Hugh C; Krishnan, Ranga R; Kumar, Anand; Lopez, Oscar L; Lyketsos, Constantine G; Mast, Benjamin T; Morris, John C; Norton, Maria C; Peavy, Guerry M; Petersen, Ronald C; Reynolds, Charles F; Salloway, Stephen; Welsh-Bohmer, Kathleen A; Yesavage, Jerome

    2006-02-01

    The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

  13. Cognition enhancers in age-related cognitive decline.

    PubMed

    Riedel, W J; Jolles, J

    1996-04-01

    A review of recently published studies on the effect of cognition enhancers in non-demented human study participants is presented. The heterogeneity of the therapeutic target, age-associated cognitive decline, can be improved by separately treating groups in whom age-extrinsic factors may underlie cognitive pathology. Standardisation of cognitive assessments is necessary, since many different tests are applied to answer the same question. Modelling cognitive dysfunction, either by pharmacological or nonpharmacological means, in humans is highly recommended since it allows hypotheses to be tested in a clearly operationalised way. Predictive validity of the currently applied models for the clinical situation remains a problem, however. The scopolamine (hyoscine) model has, to a reasonable extent, predictive validity for the cholinergic agents. The results of 67 single-dose studies and 30 multiple-dose studies are summarised. All single-dose studies and 14 multiple-dose studies were carried out in young or elderly human volunteers. In 45 of 81 volunteer studies, models of cognitive dysfunction were employed. The scopolamine model was the most used (n = 21); the other studies induced cognitive dysfunction by means of benzodiazepines (8), hypoxia (7), alcohol (5) and sleep-deprivation (4). The remaining 16 multiple-dose studies were clinical trials of a duration varying between 2 weeks and 1 year (average duration was 14 weeks). In these trials, the effects of cognition enhancers were assessed in elderly people in whom impairment of memory, psychomotor performance or cognitive function was determined. These included age-associated memory impairment (AAMI) and age-associated cognitive decline (AACD). There were many studies in which the cognition enhancing properties of substances in humans were reliably demonstrated. The cognition enhancing properties of substances that are widely used, such as caffeine, nicotine and vitamins, may already be active against AACD. New

  14. 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

  15. Cognitive decline in Huntington's disease expansion gene carriers.

    PubMed

    Baake, Verena; Reijntjes, Robert H A M; Dumas, Eve M; Thompson, Jennifer C; Roos, Raymund A C

    2017-10-01

    In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline over time is unknown. The aim of this study is to quantify the progression of cognitive decline across all HD stages, from pre-motormanifest to advanced HD, and to investigate if CAG length mediates cognitive decline. In the European REGISTRY study 2669 HD expansion gene carriers underwent annual cognitive assessment. General linear mixed models were used to model the cognitive decline for each cognitive task across all disease stages. Additionally, a model was developed to evaluate the cognitive decline based on CAG length and age rather than disease stage. There was significant cognitive decline on all administered tasks throughout pre-motormanifest (close to estimated disease onset) participants and the subsequent motormanifest participants from stage 1 to stage 4. Performance on the Stroop Word and Stroop Color tests additionally declined significantly across the two pre-motormanifest groups: far and close to estimated disease onset. The evaluation of cognition performance in relation to CAG length and age revealed a more rapid cognitive decline in participants with longer CAG length than participants with shorter CAG length over time. Cognitive performance already shows decline in pre-motormanifest HD gene expansion carriers and gradually worsens to late stage HD. HD gene expansion carriers with certain CAG length have their own cognitive profile, i.e., longer CAG length is associated with more rapid decline. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Depressed Mood Mediates Decline in Cognitive Processing Speed in Caregivers

    ERIC Educational Resources Information Center

    Vitaliano, Peter P.; Zhang, Jianping; Young, Heather M.; Caswell, Lisa W.; Scanlan, James M.; Echeverria, Diana

    2009-01-01

    Purpose: Very few studies have examined cognitive decline in caregivers versus noncaregivers, and only 1 study has examined mediators of such decline. We evaluated the relationship between caregiver status and decline on the digit symbol test (DST; a measure of processing speed, attention, cognitive-motor translation, and visual scanning) and…

  17. 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.

  18. Folic Acid Supplements: Can They Slow Cognitive Decline?

    MedlinePlus

    ... slow cognitive decline? I've heard that folic acid supplements can improve cognitive function in older adults. ... those with Alzheimer's disease also benefit from folic acid? Answers from Paul Y. Takahashi, M.D. There's ...

  19. Sensorineural Organs Dysfunction and Cognitive Decline: A Review Article

    PubMed Central

    Wongrakpanich, Supakanya; Petchlorlian, Aisawan; Rosenzweig, Andrew

    2016-01-01

    Vision, hearing, olfaction, and cognitive function are essential components of healthy and successful aging. Multiple studies demonstrate relationship between these conditions with cognitive function. The present article focuses on hearing loss, visual impairment, olfactory loss, and dual sensory impairments in relation to cognitive declination and neurodegenerative disorders. Sensorineural organ impairment is a predictive factor for mild cognitive impairment and neurodegenerative disorders in the elderly. We recommend early detection of sensorineural dysfunction by history, physical examination, and screening tests. Assisted device and early cognitive rehabilitation may be beneficial. Future research is warranted in order to explore advanced treatment options and method to slow progression for cognitive declination and sensorineural organ impairment. PMID:28053826

  20. Sensorineural Organs Dysfunction and Cognitive Decline: A Review Article.

    PubMed

    Wongrakpanich, Supakanya; Petchlorlian, Aisawan; Rosenzweig, Andrew

    2016-12-01

    Vision, hearing, olfaction, and cognitive function are essential components of healthy and successful aging. Multiple studies demonstrate relationship between these conditions with cognitive function. The present article focuses on hearing loss, visual impairment, olfactory loss, and dual sensory impairments in relation to cognitive declination and neurodegenerative disorders. Sensorineural organ impairment is a predictive factor for mild cognitive impairment and neurodegenerative disorders in the elderly. We recommend early detection of sensorineural dysfunction by history, physical examination, and screening tests. Assisted device and early cognitive rehabilitation may be beneficial. Future research is warranted in order to explore advanced treatment options and method to slow progression for cognitive declination and sensorineural organ impairment.

  1. 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

  2. Menopause Is Associated with Accelerated Lung Function Decline.

    PubMed

    Triebner, Kai; Matulonga, Bobette; Johannessen, Ane; Suske, Sandra; Benediktsdóttir, Bryndís; Demoly, Pascal; Dharmage, Shyamali C; Franklin, Karl A; Garcia-Aymerich, Judith; Gullón Blanco, José Antonio; Heinrich, Joachim; Holm, Mathias; Jarvis, Debbie; Jõgi, Rain; Lindberg, Eva; Moratalla Rovira, Jesús Martínez; Muniozguren Agirre, Nerea; Pin, Isabelle; Probst-Hensch, Nicole; Puggini, Luca; Raherison, Chantal; Sánchez-Ramos, José Luis; Schlünssen, Vivi; Sunyer, Jordi; Svanes, Cecilie; Hustad, Steinar; Leynaert, Bénédicte; Gómez Real, Francisco

    2017-04-15

    Menopause is associated with changes in sex hormones, which affect immunity, inflammation, and osteoporosis and may impair lung function. Lung function decline has not previously been investigated in relation to menopause. To study whether lung function decline, assessed by FVC and FEV1, is accelerated in women who undergo menopause. The population-based longitudinal European Community Respiratory Health Survey provided serum samples, spirometry, and questionnaire data about respiratory and reproductive health from three study waves (n = 1,438). We measured follicle-stimulating hormone and luteinizing hormone and added information on menstrual patterns to determine menopausal status using latent class analysis. Associations with lung function decline were investigated using linear mixed effects models, adjusting for age, height, weight, pack-years, current smoking, age at completed full-time education, spirometer, and including study center as random effect. Menopausal status was associated with accelerated lung function decline. The adjusted mean FVC decline was increased by -10.2 ml/yr (95% confidence interval [CI], -13.1 to -7.2) in transitional women and -12.5 ml/yr (95% CI, -16.2 to -8.9) in post-menopausal women, compared with women menstruating regularly. The adjusted mean FEV1 decline increased by -3.8 ml/yr (95% CI, -6.3 to -2.9) in transitional women and -5.2 ml/yr (95% CI, -8.3 to -2.0) in post-menopausal women. Lung function declined more rapidly among transitional and post-menopausal women, in particular for FVC, beyond the expected age change. Clinicians should be aware that respiratory health often deteriorates during reproductive aging.

  3. Inspection Time: A Biomarker for Cognitive Decline

    ERIC Educational Resources Information Center

    Gregory, Tess; Nettelbeck, Ted; Howard, Sara; Wilson, Carlene

    2008-01-01

    Inspection Time (IT) is a psychophysical speed measure that has been linked to a range of cognitive abilities with results finding that shorter IT is associated with superior performance in cognitive abilities. Following a recent suggestion by Nettelbeck and Wilson [Nettelbeck, T., & Wilson, C. (2004). The Flynn effect: Smarter not faster.…

  4. Inspection Time: A Biomarker for Cognitive Decline

    ERIC Educational Resources Information Center

    Gregory, Tess; Nettelbeck, Ted; Howard, Sara; Wilson, Carlene

    2008-01-01

    Inspection Time (IT) is a psychophysical speed measure that has been linked to a range of cognitive abilities with results finding that shorter IT is associated with superior performance in cognitive abilities. Following a recent suggestion by Nettelbeck and Wilson [Nettelbeck, T., & Wilson, C. (2004). The Flynn effect: Smarter not faster.…

  5. Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

    PubMed

    Rolstad, Sindre; Berg, Anne Ingeborg; Bjerke, Maria; Johansson, Boo; Zetterberg, Henrik; Wallin, Anders

    2013-01-01

    The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-β (Aβ42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates. In patients with subjective cognitive impairment, T-tau had a small impact on executive functions (r2 = 0.07). T-tau had a small to moderate influence (r2 = 0.06-0.11) on all cognitive functions with the exception of visuospatial functions in patients with mild cognitive impairment (MCI). In patients with dementia, the impact of T-tau was large (r2 = 0.29) on semantic memory. Aβ42 had a small effect (r2 = 0.07) on speed and executive functions in MCI. In patients with dementia, Aβ42 had a moderate influence (r2 = 0.13-0.24) on semantic and verbal working memory/fluency. Our results speak in favor of the notion that CSF biomarkers reflect the rate of cognitive decline across the continuum of cognitive impairment from healthy to dementia. CSF predicted subsequent decline in more cognitive domains among MCI cases, but the impact was most pronounced in patients with dementia.

  6. Trajectories of cognitive decline in different types of dementia.

    PubMed

    Smits, L L; van Harten, A C; Pijnenburg, Y A L; Koedam, E L G E; Bouwman, F H; Sistermans, N; Reuling, I E W; Prins, N D; Lemstra, A W; Scheltens, P; van der Flier, W M

    2015-04-01

    To investigate trajectories of cognitive decline in patients with different types of dementia compared to controls in a longitudinal study. In 199 patients with Alzheimer's disease (AD), 10 with vascular dementia (VaD), 26 with dementia with Lewy bodies (DLB), 20 with behavioural variant frontotemporal dementia (bvFTD), 15 with language variant frontotemporal dementia (lvFTD) and 112 controls we assessed five cognitive domains: memory, language, attention, executive and visuospatial functioning, and global cognition (Mini-Mental State Examination, MMSE). All subjects had at least two neuropsychological assessments (median 2, range 2-7). Neuropsychological data were standardized into z scores using baseline performance of controls as reference. Linear mixed models (LMMs) were used to estimate baseline cognitive functioning and cognitive decline over time for each group, adjusted for age, gender and education. At baseline, patients with dementia performed worse than controls in all cognitive domains (p < 0.05) except visuospatial functioning, which was only impaired in patients with AD and DLB (p < 0.001). During follow-up, patients with AD declined in all cognitive domains (p < 0.001). DLB showed decline in every cognitive domain except language and global cognition. bvFTD showed rapid decline in memory, language, attention and executive functioning (all p < 0.01) whereas visuospatial functioning remained fairly stable. lvFTD declined mostly in attention and executive functioning (p < 0.01). VaD showed decline in attention and executive functioning. We show cognitive trajectories of different types of dementia. These estimations of natural disease course have important value for the design of clinical trials as neuropsychological measures are increasingly being used as outcome measures.

  7. 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

  8. 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

  9. TDP-43 pathology, cognitive decline, and dementia in old age.

    PubMed

    Wilson, Robert S; Yu, Lei; Trojanowski, John Q; Chen, Er-Yun; Boyle, Patricia A; Bennett, David A; Schneider, Julie A

    2013-11-01

    Cognitive decline is a leading cause of disability and death in old age but its neurobiological bases are not well understood. To test the hypothesis that transactive response DNA-binding protein 43 (TDP-43) is related to late-life cognitive decline. Longitudinal clinical-pathologic cohort study involving more than 40 Catholic groups across the United States. A total of 130 older Catholic nuns, priests, and monks underwent annual clinical evaluations, including detailed cognitive testing, for a mean of 10.1 years prior to death. On neuropathologic examination, we collected semiquantitative measures of TDP-43 pathology, density of neuronal neurofibrillary tangles, area occupied by amyloid-beta plaques, and the presence of alpha-synuclein Lewy bodies from multiple brain regions. Gross and microscopic cerebral infarcts and hippocampal sclerosis were also identified. Annual rate of change in a previously established composite measure of global cognition during a mean of 10.1 years of annual observation before death. Transactive response DNA-binding protein 43 pathology, ranging from sparse to severe, was identified in 46% of participants and was associated with amyloid plaques, tangles, and hippocampal sclerosis but not neocortical Lewy bodies or cerebral infarcts. After controlling for amyloid plaques, tangles, and hippocampal sclerosis, TDP-43 pathology was associated with more rapid cognitive decline and accounted for nearly as much of the variability in rates of global cognitive decline as did tangles. Transactive response DNA-binding protein 43 pathology had a distinct cognitive profile that differed from other neuropathologic processes (related to decline in episodic and working memory but not in other cognitive domains), and it was elevated in those who developed dementia but not in those with mild cognitive impairment. The results suggest that TDP-43 is an important brain pathology underlying cognitive decline and dementia in old age.

  10. Nutritional management of older adults with cognitive decline and dementia.

    PubMed

    Ogawa, Sumito

    2014-04-01

    Age-related cognitive decline is a main predictor of disability among elderly people, and with the continued expansion of the aging population and the increase in life expectancy, the prevalence of mild cognitive impairment and dementia represented by Alzheimer's disease (AD), which is a multifactorial neurodegenerative disorder of older adults, have increased. Recent epidemiological and observational studies suggest a relationship exists between lifestyle factors, including nutrition and diet, and cognitive function in aging adults. It is also suggested that malnutrition and nutrient deficiencies are associated with cognitive decline in patients with dementia. There are a variety of nutritional factors, including nutritional status and dietary patterns, that might be associated with cognitive function, and specific micronutrients and dietary components have been suggested to have an association with cognitive function as well. Based on these findings and evidence, evaluation of nutritional state, as well as nutritional intervention, might be able to play a role in the management and prevention of dementia.

  11. Excessive sleepiness is predictive of cognitive decline in the elderly.

    PubMed

    Jaussent, Isabelle; Bouyer, Jean; Ancelin, Marie-Laure; Berr, Claudine; Foubert-Samier, Alexandra; Ritchie, Karen; Ohayon, Maurice M; Besset, Alain; Dauvilliers, Yves

    2012-09-01

    To examine the association of sleep complaints reported at baseline (insomnia complaints and excessive daytime sleepiness (EDS)) and medication, with cognitive decline in community-dwelling elderly. An 8-yr longitudinal study. The French Three-City Study. There were 4,894 patients without dementia recruited from 3 French cities and having a Mini-Mental Status Examination (MMSE) score ≥ 24 points at baseline. Questionnaires were used to evaluate insomnia complaints (poor sleep quality (SQ), difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), early morning awakening (EMA)), EDS, and sleep medication at baseline. Cognitive decline was defined as a 4-point reduction in MMSE score during follow-up at 2, 4, and 8 yr. Logistic regression models were adjusted for sociodemographic, behavioral, physical, and mental health variables, and apolipoprotein E genotype. EDS independently increased the risk of cognitive decline (odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.02-1.56), especially for those patients who also developed dementia during the follow-up period (OR = 1.39, 95% CI = 1.00-1.97). The number of insomnia complaints and DMS were negatively associated with MMSE cognitive decline (OR = 0.77, 95% CI = 0.60-0.98 for 3-4 complaints, OR = 0.81, 95% CI = 0.68-0.96, respectively). The 3 other components of insomnia (SQ, DIS, EMA) were not significantly associated with MMSE cognitive decline. Our results suggest that EDS may be associated independently with the risk of cognitive decline in the elderly population. Such results could have important public health implications because EDS may be an early marker and potentially reversible risk factor of cognitive decline and onset of dementia.

  12. 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

  13. Should we screen for cognitive decline and dementia?

    PubMed

    Calzà, Laura; Beltrami, Daniela; Gagliardi, Gloria; Ghidoni, Enrico; Marcello, Norina; Rossini-Favretti, Rema; Tamburini, Fabio

    2015-09-01

    Due to increased life expectancy, the prevalence of cognitive decline related to neurodegenerative diseases and to non-neurological conditions is increasing in western countries. As with other diseases, the burden might be reduced through personalized interventions delivered at early stages of the disease. Thus, there is an increasing demand, from both social and healthcare systems, for instruments and strategies to recognize cognitive decline, and possibly distinguish the precursor of serious neurodegeneration from "benign senile forgetfulness" or the temporary consequences of illness or trauma. However, this goal faces both technical and ethical issues. In this article we deal with the following: (i) re-definition of cognitive decline and its relationship with frailty definitions, starting from the recent work of international consensus groups for presymptomatic Alzheimer disease recognition; (ii) ethical problems concerning anonymous and personalized cognitive screening and the need for appropriate counselling; (iii) the need for more sensitive and specific tools to detect and distinguish pathological levels of cognitive decline and delineate the contribution of non-pathological decline to accumulated frailty impacts and (iv) the potential of the language domain and spontaneous speech analyses. Copyright © 2015. Published by Elsevier Ireland Ltd.

  14. Infectious Burden and Cognitive Decline in the Northern Manhattan Study

    PubMed Central

    Wright, Clinton B.; Gardener, Hannah; Dong, Chuanhui; Yoshita, Mitsuhiro; DeCarli, Charles; Sacco, Ralph L.; Stern, Yaakov; Elkind, Mitchell S.V.

    2016-01-01

    Objectives To determine whether infectious burden (IB) is associated with worse performance and decline on a battery of neuropsychological tests. Design Prospective cohort study (Northern Manhattan Study (NOMAS)). Setting Community. Participants A subsample of 588 stroke-free NOMAS participants with IB and cognitive data (mean age 71±8, 62% female, 14% white, 16% black, 70% Hispanic) and 419 with repeat cognitive testing. Measurements Samples used for IB data were collected at baseline. Two waves of neurocognitive assessments occurred during follow-up. Participants underwent a neuropsychological battery and had repeated testing (mean time span 6±2 years). Using factor analysis–derived domain-specific Z scores for language, memory, executive function, and processing speed, associations between a quantitative stroke risk-weighted IB index (IBI), based on five common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, herpes simplex viruses 1 and 2), and cognitive performance and decline in each domain was examined. Results Adjusting for demographic characteristics, socioeconomic status, crystallized cognitive abilities, and vascular risk factors, the IBI was inversely associated with executive function at baseline (beta=−0.10, p=.01) but not with baseline language, memory, or processing speed performance in adjusted analyses. The IBI was associated with cognitive decline in the memory domain, adjusting for demographic and vascular risk factors (p=.02). Conclusion A quantitative measure of IB explained variability in baseline executive function performance and associated with decline in memory. Past exposure to common infections may contribute to vascular cognitive impairment and warrants further study. PMID:26289683

  15. Which factors predict cognitive decline in Parkinson's disease?

    PubMed Central

    Caparros-Lefebvre, D; Pécheux, N; Petit, V; Duhamel, A; Petit, H

    1995-01-01

    The study assessed cognitive decline in non-demented, non-depressed patients with well defined Parkinson's disease and determined the predictive value for cognitive decline of different motor symptoms. Motor disability was measured with the Unified Parkinson's disease rating scale, impairment in activities of daily living, levodopa test, and long term clinical follow up. Neuropsychological evaluations included modified mini mental state, fluency, Wechsler logical memory, Wisconsin card sorting test, and the Montgomery and Asberg depression rating scale. Fifty three patients fulfilling clinical criteria for idiopathic Parkinson's disease were studied. Cognitive performance on initial testing was significantly correlated with education and disease duration but not with age at disease onset. Cognitive performance on retesting after three years of follow up was significantly reduced. This reduction was significantly greater in the late onset group, in patients with isolated dystonic dyskinesiae, and in patients with a lower percentage of motor improvement on levodopa. Cognitive decline in idiopathic Parkinson's disease may depend on both the prevalence of non-dopaminergic lesions and the topography of dopaminergic denervation. Predictive factors for cognitive decline, especially in executive tasks, relate more to non-dopaminergic than to dopaminergic lesions. PMID:7823067

  16. Diagnosing early cognitive decline-When, how and for whom?

    PubMed

    Allan, Charlotte L; Behrman, Sophie; Ebmeier, Klaus P; Valkanova, Vyara

    2017-02-01

    Mild cognitive impairment (MCI) is a term used to describe cognitive impairment in one or more cognitive domains that is greater than any expected age-related changes, but not of the magnitude to warrant a diagnosis of dementia. This review considers how early cognitive decline is diagnosed, focusing on the use of neuropsychological tests and neuroimaging, as well as the differential diagnosis. Potential treatments, including secondary prevention, post-diagnostic support and self-help are discussed. Finally, medico-legal matters such as driving, lasting power of attorney and employment are outlined.

  17. Subtle Cognitive Decline and Biomarker Staging in Preclinical Alzheimer's Disease.

    PubMed

    Edmonds, Emily C; Delano-Wood, Lisa; Galasko, Douglas R; Salmon, David P; Bondi, Mark W

    2015-01-01

    The NIA-AA criteria for "preclinical" Alzheimer's disease (AD) propose a staging method in which AD biomarkers follow an invariable temporal sequence in accordance with the amyloid cascade hypothesis. However, recent findings do not align with the proposed temporal sequence and "subtle cognitive decline," which has not been definitively operationalized, may occur earlier than suggested in preclinical AD. We aimed to define "subtle cognitive decline" using sensitive and reliable neuropsychological tests, and to examine the number and sequence of biomarker abnormalities in the Alzheimer's Disease Neuroimaging Initiative (ADNI). 570 cognitively normal ADNI participants were classified based on NIA-AA criteria and separately based on the number of abnormal biomarkers/cognitive markers associated with preclinical AD that each individual possessed. Results revealed that neurodegeneration alone was 2.5 times more common than amyloidosis alone at baseline. For those who demonstrated only one abnormal biomarker at baseline and later progressed to mild cognitive impairment/AD, neurodegeneration alone was most common, followed by amyloidosis alone or subtle cognitive decline alone, which were equally common. Findings suggest that most individuals do not follow the temporal order proposed by NIA-AA criteria. We provide an operational definition of subtle cognitive decline that captures both cognitive and functional decline. Additionally, we offer a new approach for staging preclinical AD based on number of abnormal biomarkers, without regard to their temporal order of occurrence. This method of characterizing preclinical AD is more parsimonious than the NIA-AA staging system and does not presume that all patients follow a singular invariant expression of the disease.

  18. Cognitive decline, dietary factors and gut-brain interactions.

    PubMed

    Caracciolo, Barbara; Xu, Weili; Collins, Stephen; Fratiglioni, Laura

    2014-01-01

    Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. We reviewed the most recent findings in this rapidly expanding field. Some nutrients, such as vitamins and fatty acids, have been studied longer than others, but strong scientific evidence of an association is lacking even for these compounds. Specific dietary patterns, like the Mediterranean diet, may be more beneficial than a high consumption of single nutrients or specific food items. A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation.

  19. Entorhinal cortex thickness predicts cognitive decline in Alzheimer's disease.

    PubMed

    Velayudhan, Latha; Proitsi, Petroula; Westman, Eric; Muehlboeck, J-Sebastian; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilkka; Spenger, Christian; Hodges, Angela; Powell, John; Lovestone, Simon; Simmons, Andrew

    2013-01-01

    Biomarkers for Alzheimer's disease (AD) based on non-invasive methods are highly desirable for diagnosis, disease progression, and monitoring therapeutics. We aimed to study the use of hippocampal volume, entorhinal cortex (ERC) thickness, and whole brain volume (WBV) as predictors of cognitive change in patients with AD. 120 AD subjects, 106 mild cognitive impairment (MCI), and 99 non demented controls (NDC) from the multi-center pan-European AddNeuroMed study underwent MRI scanning at baseline and clinical evaluations at quarterly follow-up up to 1 year. The rate of cognitive decline was estimated using cognitive outcomes, Mini-Mental State Examination (MMSE) and Alzheimer disease assessment scale-cognitive (ADAS-cog) by fitting a random intercept and slope model. AD subjects had smaller ERC thickness and hippocampal and WBV volumes compared to MCI and NDC subjects. Within the AD group, ERC > WBV was significantly associated with baseline cognition (MMSE, ADAS-cog) and disease severity (Clinical Dementia Rating). Baseline ERC thickness was associated with both longitudinal MMSE and ADAS-cog score changes and WBV with ADAS-cog decline. These data indicate that AD subjects with thinner ERC had lower baseline cognitive scores, higher disease severity, and predicted greater subsequent cognitive decline at one year follow up. ERC is a region known to be affected early in the disease. Therefore, the rate of atrophy in this structure is expected to be higher since neurodegeneration begins earlier. Focusing on structural analyses that predict decline can identify those individuals at greatest risk for future cognitive loss. This may have potential for increasing the efficacy of early intervention.

  20. Predictors of ageing-related decline across multiple cognitive functions.

    PubMed

    Ritchie, Stuart J; Tucker-Drob, Elliot M; Cox, Simon R; Corley, Janie; Dykiert, Dominika; Redmond, Paul; Pattie, Alison; Taylor, Adele M; Sibbett, Ruth; Starr, John M; Deary, Ian J

    2016-01-01

    It is critical to discover why some people's cognitive abilities age better than others'. We applied multivariate growth curve models to data from a narrow-age cohort measured on a multi-domain IQ measure at age 11 years and a comprehensive battery of thirteen measures of visuospatial, memory, crystallized, and processing speed abilities at ages 70, 73, and 76 years (n = 1091 at age 70). We found that 48% of the variance in change in performance on the thirteen cognitive measures was shared across all measures, an additional 26% was specific to the four ability domains, and 26% was test-specific. We tested the association of a wide variety of sociodemographic, fitness, health, and genetic variables with each of these cognitive change factors. Models that simultaneously included all covariates accounted for appreciable proportions of variance in the cognitive change factors (e.g. approximately one third of the variance in general cognitive change). However, beyond physical fitness and possession of the APOE e4 allele, very few predictors were incrementally associated with cognitive change at statistically significant levels. The results highlight a small number of factors that predict differences in cognitive ageing, and underscore that correlates of cognitive level are not necessarily predictors of decline. Even larger samples will likely be required to identify additional variables with more modest associations with normal-range heterogeneity in aging-related cognitive declines.

  1. Vascular risk factors, cognitive decline, and dementia.

    PubMed

    Duron, E; Hanon, Olivier

    2008-01-01

    Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer's disease) and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer's disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.

  2. Rapid cognitive decline: not always Creutzfeldt-Jakob disease.

    PubMed

    Randall, A; Ellis, R; Hywel, B; Davies, R R; Alusi, S H; Larner, A J

    2015-01-01

    A patient with rapidly progressive cognitive decline over an approximately four month period was suspected to have sporadic Creutzfeldt-Jakob disease. Features thought to support this diagnosis included psychiatric symptoms (anxiety and depression), visual hallucinations and a visual field defect. However, the finding of papilloedema broadened the differential diagnosis. Although standard brain imaging and electroencephalography had shown only non-specific abnormalities, subsequent cerebral angiography disclosed an intracranial dural arteriovenous fistula. Following embolisation, the patient made a good functional recovery. Intracranial dural arteriovenous fistula merits consideration in any patient with subacute cognitive decline, and should be included in the differential diagnosis of sporadic Creutzfeldt-Jakob disease.

  3. Predictors of cognitive decline after chemotherapy in breast cancer patients.

    PubMed

    Vearncombe, Katharine J; Rolfe, Margaret; Wright, Margaret; Pachana, Nancy A; Andrew, Brooke; Beadle, Geoffrey

    2009-11-01

    The objective of this study is to identify whether decline in cognitive functioning after chemotherapy in women with breast cancer is associated with health/disease, treatment, and psychological variables. Neuropsychological performance, health/disease, and treatment-related information of 136 women with breast cancer (age M = 49.38; SD = 7.92; range = 25.25-67.92) was assessed pre-chemotherapy and 1-month post-chemotherapy. The Reliable Change Index corrected for practice (RCIp) identified women whose performance significantly declined, while Pearson correlations assessed the relationship between cognitive change and predictor variables. A total of 16.9% of women showed significant decline post-chemotherapy, with affected domains including verbal learning and memory, abstract reasoning, and motor coordination. Decline in hemoglobin levels and increased anxiety over the course of chemotherapy was found to significantly predict impairment in multiple cognitive measures. Change in specific cognitive measures was significantly associated with baseline fatigue, depression, and functional well-being (r = 0.23 to 0.33; p = .01 to < .001). Although the effects are small, there is evidence that psychological and health factors may increase vulnerability to cognitive dysfunction after chemotherapy for breast cancer. Significant associations reported in this study may be useful in the identification and treatment of at-risk individuals.

  4. Neighborhood Integration and Connectivity Predict Cognitive Performance and Decline

    PubMed Central

    Ferdous, Farhana; Diaz Moore, Keith; Burns, Jeffrey M.

    2015-01-01

    Objective: Neighborhood characteristics may be important for promoting walking, but little research has focused on older adults, especially those with cognitive impairment. We evaluated the role of neighborhood characteristics on cognitive function and decline over a 2-year period adjusting for measures of walking. Method: In a study of 64 older adults with and without mild Alzheimer’s disease (AD), we evaluated neighborhood integration and connectivity using geographical information systems data and space syntax analysis. In multiple regression analyses, we used these characteristics to predict 2-year declines in factor analytically derived cognitive scores (attention, verbal memory, mental status) adjusting for age, sex, education, and self-reported walking. Results: Neighborhood integration and connectivity predicted cognitive performance at baseline, and changes in cognitive performance over 2 years. The relationships between neighborhood characteristics and cognitive performance were not fully explained by self-reported walking. Discussion: Clearer definitions of specific neighborhood characteristics associated with walkability are needed to better understand the mechanisms by which neighborhoods may impact cognitive outcomes. These results have implications for measuring neighborhood characteristics, design and maintenance of living spaces, and interventions to increase walking among older adults. We offer suggestions for future research measuring neighborhood characteristics and cognitive function. PMID:26504889

  5. Both Financial and Cognitive Decline Predict Clinical Progression in MCI

    PubMed Central

    Gerstenecker, Adam; Triebel, Kristen L.; Martin, Roy; Snyder, Scott; Marson, Daniel C.

    2015-01-01

    We investigated the roles of financial/functional and cognitive abilities in predicting clinical progression in patients with mild cognitive impairment (MCI). In a longitudinal sample of 51 patients with consensus-conference diagnosed MCI likely due to Alzheimer’s disease (AD). Two-year change scores were calculated for a performance measure of functional ability, cognitive variables, and three outcome measures used to track progression in neurologic disorders. We examined patterns of financial and cognitive decline across the two-year study period, and used this data and the three outcome variables to construct discrete predictor models of clinical progression in MCI. We found that both financial skills and cognitive abilities declined over the two-year study period, were significantly associated with clinical progression, and contributed unique variance all three predictor models. The resulting models accounted for 40–75% of variance in clinical progression across outcome variables. Taken together, our results indicate that changes in both cognitive abilities and higher-order functional skills appear integral to understanding clinical progression in MCI likely due to AD. Specifically, declines in financial skills contribute unique variance to measures commonly used to track progression in neurological disorders associated with aging and thus represent an important functional marker of clinical progression in prodromal AD. PMID:26900988

  6. Both Financial and Cognitive Decline Predict Clinical Progression in MCI.

    PubMed

    Gerstenecker, Adam; Triebel, Kristen L; Martin, Roy; Snyder, Scott; Marson, Daniel C

    2016-01-01

    We investigated the roles of financial/functional and cognitive abilities in predicting clinical progression in patients with mild cognitive impairment (MCI). In a longitudinal sample of 51 patients with consensus conference diagnosed MCI likely due to Alzheimer disease (AD), two-year change scores were calculated for a performance measure of functional ability, cognitive variables, and 3 outcome measures used to track progression in neurological disorders. We examined patterns of financial and cognitive decline across the 2-year study period, and used these data and the 3 outcome variables to construct discrete predictor models of clinical progression in MCI. We found that both financial skills and cognitive abilities declined over the 2-year study period, were significantly associated with clinical progression, and contributed unique variance to all 3 predictor models. The resulting models accounted for 40% to 75% of variance in clinical progression across outcome variables. Taken together, our results indicate that changes in both cognitive abilities and higher order functional skills appear integral to understanding clinical progression in MCI likely due to AD. Specifically, declines in financial skills contribute unique variance to measures commonly used to track progression in neurological disorders associated with aging, and thus represent an important functional marker of clinical progression in prodromal AD.

  7. Healthy obesity and risk of accelerated functional decline and disability.

    PubMed

    Bell, J A; Sabia, S; Singh-Manoux, A; Hamer, M; Kivimäki, M

    2017-06-01

    obesity, even if metabolically healthy, accelerates age-related declines in functional ability and poses a threat to independence in older age.

  8. IANA task force on nutrition and cognitive decline with aging.

    PubMed

    Gillette Guyonnet, S; Abellan Van Kan, G; Andrieu, S; Barberger Gateau, P; Berr, C; Bonnefoy, M; Dartigues, J F; de Groot, L; Ferry, M; Galan, P; Hercberg, S; Jeandel, C; Morris, M C; Nourhashemi, F; Payette, H; Poulain, J P; Portet, F; Roussel, A M; Ritz, P; Rolland, Y; Vellas, B

    2007-01-01

    Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta

  9. 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.

  10. Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

    PubMed

    Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

    2016-06-01

    Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  11. 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.

  12. Cognitive Decline and Aging: The role of Concussive and Subconcussive Impacts

    PubMed Central

    Broglio, Steven P; Eckner, James T.; Paulson, Henry L; Kutcher, Jeffrey S.

    2013-01-01

    Concussion has been viewed historically as a transient injury with no evidence supporting the existence of persistent effects. However, our recent work demonstrates electroencephalographic and motor control changes in otherwise healthy individuals with a history of concussion. We therefore hypothesize that concussive and subconcussive head impacts set about a cascade of pathological events that accelerates declines in cognitive function typically associated with the aging process. PMID:22728452

  13. Computational model of sustained acceleration effects on human cognitive performance.

    PubMed

    McKinlly, Richard A; Gallimore, Jennie J

    2013-08-01

    Extreme acceleration maneuvers encountered in modern agile fighter aircraft can wreak havoc on human physiology, thereby significantly influencing cognitive task performance. As oxygen content declines under acceleration stress, the activity of high order cortical tissue reduces to ensure sufficient metabolic resources are available for critical life-sustaining autonomic functions. Consequently, cognitive abilities reliant on these affected areas suffer significant performance degradations. The goal was to develop and validate a model capable of predicting human cognitive performance under acceleration stress. Development began with creation of a proportional control cardiovascular model that produced predictions of several hemodynamic parameters, including eye-level blood pressure and regional cerebral oxygen saturation (rSo2). An algorithm was derived to relate changes in rSo2 within specific brain structures to performance on cognitive tasks that require engagement of different brain areas. Data from the "precision timing" experiment were then used to validate the model predicting cognitive performance as a function of G(z) profile. The following are value ranges. Results showed high agreement between the measured and predicted values for the rSo2 (correlation coefficient: 0.7483-0.8687; linear best-fit slope: 0.5760-0.9484; mean percent error: 0.75-3.33) and cognitive performance models (motion inference task--correlation coefficient: 0.7103-0.9451; linear best-fit slope: 0.7416-0.9144; mean percent error: 6.35-38.21; precision timing task--correlation coefficient: 0.6856-0.9726; linear best-fit slope: 0.5795-1.027; mean percent error: 6.30-17.28). The evidence suggests that the model is capable of accurately predicting cognitive performance of simplistic tasks under high acceleration stress.

  14. Monounsaturated, trans & saturated fatty acids and cognitive decline in women

    PubMed Central

    Naqvi, Asghar Z.; Harty, Brian; Mukamal, Kenneth J.; Stoddard, Anne M.; Vitolins, Mara; Dunn, Julie E.

    2011-01-01

    Objectives Prospectively assess effects of select dietary fats on cognitive decline Design Prospective observational; 3-year follow-up Setting Subjects recruited at Northwestern University who participated in Women's Health Initiative Observational Study or control group of Diet Modification arm. Participants 482 women ≥ 60 years Measurements We averaged dietary intake from a validated food frequency questionnaire (FFQ) administered twice (mean=2.7 years apart) before baseline cognitive assessment (mean=2.9 years after 2nd FFQ). Testing of memory, vision, executive function, language, and attention was performed at 2 time points, 3 years apart. We created a global Z-score for both time points by averaging all Z-scores for each participant and defined global cognitive change as the difference between follow-up and baseline Z-scores. Results Median intakes of saturated fats (SFA), trans-fats, (TFA), dietary cholesterol (DC) and monounsaturated fats (MUFA) were 18.53 g/d, 3.45 g/d, 0.201 g/d and 19.39 g/d, respectively. There were no associations between degree of cognitive decline and intakes of SFA (p=0.69), TFA (p=0.54) or DC (p=0.64) after adjusting for baseline cognition, total energy, age, education, reading ability, Apolipoprotein E (ε4) allele, BMI, estrogen and beta-blocker use, and intake of caffeine and other fatty acids. In contrast, compared with participants in the lowest quartile, MUFA intake was associated with lower cognitive decline in fully adjusted linear regression models, with decline of 0.21 + 0.05 SE in the lowest versus 0.05 + 0.05 SE in the highest quartiles (p=0.02). This effect of MUFA intake was primarily in the visual and memory domains (p=0.03 for both). Conclusion Higher intakes of SFA, TFA and DC in these women were not associated with cognitive decline, while MUFA intake was associated with less cognitive decline. PMID:21568955

  15. Cognitive decline in prodromal Huntington Disease: implications for clinical trials.

    PubMed

    Paulsen, Jane S; Smith, Megan M; Long, Jeffrey D

    2013-11-01

    Controversy exists regarding the feasibility of preventive clinical trials in prodromal Huntington disease (HD). A primary limitation is a lack of outcome measures for persons with the gene mutation who have not yet been diagnosed with HD. Many longitudinal studies of cognitive decline in prodromal HD have not stratified samples based on disease progression, thereby obscuring differences between symptomatic and nonsymptomatic individuals. Prodromal participants from PREDICT-HD were stratified by disease progression into one of three groups: those having a High, Medium, or Low probability of motor manifestation within the next 5 years. Data from a total of N=1299 participants with up to 5950 data points were subjected to linear mixed effects regression on 29 longitudinal cognitive variables, controlling for age, education, depression, and gender. Performance of the three prodromal HD groups was characterised by insidious and significant cognitive decline over time. Twenty-one variables from 19 distinct cognitive tasks revealed evidence of a disease progression gradient, meaning that the rate of deterioration varied as a function of progression level, with faster deterioration associated with greater disease progression. Nineteen measures showed significant longitudinal change in the High group, nine showed significant change in the Medium group and four showed significant cognitive decline in the Low group. Results indicate that clinical trials may be conducted in prodromal HD using the outcome measures and methods specified. The findings may help inform interventions in HD as well as other neurodegenerative disorders.

  16. Improved diabetes control in the elderly delays global cognitive decline.

    PubMed

    Luchsinger, J A; Palmas, W; Teresi, J A; Silver, S; Kong, J; Eimicke, J P; Weinstock, R S; Shea, S

    2011-06-01

    To examine whether improved diabetes control is related to better cognitive outcomes. Randomized control trial. A randomized trial of telemedicine vs. usual care in elderly persons with type 2 diabetes. Participants were 2169 persons 55 years and older with type 2 diabetes from New York City and Upstate New York. The diabetes case management intervention was implemented by a diabetes nurse, via a telemedicine unit in the participant's home, and in coordination with the primary care physician. Hemoglobin A1c (HbA1c), systolic blood pressure (SBP), and low density lipoprotein cholesterol (LDL), were measured at a baseline visit and at up to 5 annual follow-up visits. Global cognition was measured at those visits with the Comprehensive Assessment and Referral Evaluation (CARE). In mixed models the intervention was related to slower global cognitive decline in the intervention group (p = 0.01). Improvements in HbA1c (p = 0.03), but not SBP or LDL, mediated the effect of the intervention on cognitive decline. Improved diabetes control in the elderly following existing guidelines through a telemedicine intervention was associated with less global cognitive decline. The main mediator of this effect seemed to be improvements in HbA1c.

  17. Dietary patterns, cognitive decline, and dementia: a systematic review.

    PubMed

    van de Rest, Ondine; Berendsen, Agnes Am; Haveman-Nies, Annemien; de Groot, Lisette Cpgm

    2015-03-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline.

  18. Dietary Patterns, Cognitive Decline, and Dementia: A Systematic Review12

    PubMed Central

    van de Rest, Ondine; Berendsen, Agnes AM; Haveman-Nies, Annemien; de Groot, Lisette CPGM

    2015-01-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline. PMID:25770254

  19. Infectious Burden and Cognitive Decline in the Northern Manhattan Study.

    PubMed

    Wright, Clinton B; Gardener, Hannah; Dong, Chuanhui; Yoshita, Mitsuhiro; DeCarli, Charles; Sacco, Ralph L; Stern, Yaakov; Elkind, Mitchell S V

    2015-08-01

    To determine whether infectious burden (IB) is associated with worse performance and decline on a battery of neuropsychological tests. Prospective cohort study (Northern Manhattan Study (NOMAS)). Community. A subsample of 588 stroke-free NOMAS participants with IB and cognitive data (mean age 71 ± 8, 62% female, 14% white, 16% black, 70% Hispanic) and 419 with repeat cognitive testing. Samples used for IB data were collected at baseline. Two waves of neurocognitive assessments occurred during follow-up. Participants underwent a neuropsychological battery and had repeated testing (mean time span 6 ± 2 years). Using factor analysis-derived domain-specific Z scores for language, memory, executive function, and processing speed, associations between a quantitative stroke risk-weighted IB index (IBI), based on five common infections (Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, herpes simplex viruses 1 and 2), and cognitive performance and decline in each domain was examined. Adjusting for demographic characteristics, socioeconomic status, crystallized cognitive abilities, and vascular risk factors, the IBI was inversely associated with executive function at baseline (beta = -0.10, P = .01) but not with baseline language, memory, or processing speed performance in adjusted analyses. The IBI was associated with cognitive decline in the memory domain, adjusting for demographic and vascular risk factors (P = .02). A quantitative stroke risk-weighted measure of IB explained variability in baseline executive function performance and associated with decline in memory. Past exposure to common infections may contribute to vascular cognitive impairment and warrants further study. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  20. Cognitive declines precede and predict functional declines in aging and Alzheimer's disease.

    PubMed

    Zahodne, Laura B; Manly, Jennifer J; MacKay-Brandt, Anna; Stern, Yaakov

    2013-01-01

    To investigate the temporal ordering of cognitive and functional declines separately in older adults with or without Alzheimer's disease (AD). A community-based longitudinal study of aging and dementia in Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging Project) and a multicenter, clinic-based longitudinal study of prevalent AD at Columbia University Medical Center, Johns Hopkins School of Medicine, Massachusetts General Hospital, and the Hôpital de la Salpêtrière in Paris, France (the Predictors Study). 3,443 initially non-demented older adults (612 with eventual incident dementia) and 517 patients with AD. Cognitive measures included the modified Mini-Mental State Exam and composite scores of memory and language derived from a standardized neuropsychological battery. Function was measured with the Blessed Dementia Rating Scale, completed by the participant (in the sample of non-demented older adults) or an informant (in the sample of prevalent AD patients). Data were analyzed with autoregressive cross-lagged panel analysis. Cognitive scores more consistently predicted subsequent functional abilities than vice versa in non-demented older adults, participants with eventual incident dementia, and patients with prevalent AD. Cognitive declines appear to precede and cause functional declines prior to and following dementia diagnosis. Standardized neuropsychological tests are valid predictors of later functional changes in both non-demented and demented older adults.

  1. Visuomotor adaptability in older adults with mild cognitive decline.

    PubMed

    Schaffert, Jeffrey; Lee, Chi-Mei; Neill, Rebecca; Bo, Jin

    2017-02-01

    The current study examined the augmentation of error feedback on visuomotor adaptability in older adults with varying degrees of cognitive decline (assessed by the Montreal Cognitive Assessment; MoCA). Twenty-three participants performed a center-out computerized visuomotor adaptation task when the visual feedback of their hand movement error was presented in a regular (ratio=1:1) or enhanced (ratio=1:2) error feedback schedule. Results showed that older adults with lower scores on the MoCA had less adaptability than those with higher MoCA scores during the regular feedback schedule. However, participants demonstrated similar adaptability during the enhanced feedback schedule, regardless of their cognitive ability. Furthermore, individuals with lower MoCA scores showed larger after-effects in spatial control during the enhanced schedule compared to the regular schedule, whereas individuals with higher MoCA scores displayed the opposite pattern. Additional neuro-cognitive assessments revealed that spatial working memory and processing speed were positively related to motor adaptability during the regular scheduled but negatively related to adaptability during the enhanced schedule. We argue that individuals with mild cognitive decline employed different adaptation strategies when encountering enhanced visual feedback, suggesting older adults with mild cognitive impairment (MCI) may benefit from enhanced visual error feedback during sensorimotor adaptation.

  2. Cognitive decline in older Mexican Americans with diabetes.

    PubMed Central

    Rotkiewicz-Piorun, Anna M.; Al Snih, Soham; Raji, Mukaila A.; Kuo, Yong-Fang; Markides, Kyriakos S.

    2006-01-01

    OBJECTIVE: To examine social, demographic and health factors associated with cognitive decline over a seven-year period among older Mexican Americans with diabetes. METHODS: A population-based sample of 808 noninstitutionalized Mexican Americans aged >65 years with diabetes who had a Mini-Mental State Examination (MMSE) >17 at baseline from the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE). Measurements included sociodemographics, diabetic treatment received (oral hypoglycemic or insulin), self-reported medical conditions, self-reported diabetes-related complications, high depressive symptoms and ADL limitations. RESULTS: The mean MMSE score at baseline was 25.3 + (SD=3.7). The rate of decline in cognitive function (MMSE) during the follow-up period was 0.37 point per year. Using general linear mixed models, we found that being male, and having high depressive symptoms and diabetic complications (kidney impairment, circulation problems or limb amputation) were factors significantly associated with greater declines in MMSE score over time. CONCLUSION: Circulation problems, kidney impairment and depression are the major factors associated with cognitive decline in older Mexican Americans with diabetes. PMID:17128695

  3. Can education rescue genetic liability for cognitive decline?

    PubMed

    Cook, C Justin; Fletcher, Jason M

    2015-02-01

    Although there is a vast literature linking education and later health outcomes, the mechanisms underlying these associations are relatively unknown. In the spirit of some medical literature that leverages developmental abnormalities to understand mechanisms of normative functioning, we explore the ability of higher educational attainments to "rescue" biological/genetic liabilities in brain function through inheritance of a variant of the APOE gene shown to lead to cognitive decline, dementia, and Alzheimer's disease in old age. Deploying a between-sibling design that allows quasi-experimental variation in genotype and educational attainment within a standard gene-environment interaction framework, we show evidence that the genetic effects of the "risky" APOE variant on old-age cognitive decline are absent in individuals who complete college (vs. high school graduates). Auxiliary analyses suggest that the likely mechanisms of education are most consistent through changing brain processes (i.e., "how we think") and potentially building cognitive reserves, rather than alleviating old age cognitive decline through the channels of higher socioeconomic status and resources over the life course. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Exposure to Particulate Air Pollution and Cognitive Decline in Older Women

    PubMed Central

    Weuve, Jennifer; Puett, Robin C.; Schwartz, Joel; Yanosky, Jeff D.; Laden, Francine; Grodstein, Francine

    2013-01-01

    Background Chronic exposure to particulate air pollution may accelerate cognitive decline in older adults, although data on this association are limited. Our objective was to examine long-term exposure to particulate matter (PM) air pollution, both coarse ([PM 2.5–10 μm in diameter [PM2.5-10]) and fine (PM <2.5 μm in diameter [PM2.5]), in relation to cognitive decline. Methods The study population comprised the Nurses’ Health Study Cognitive Cohort, which included 19 409 US women aged 70 to 81 years. We used geographic information system–based spatiotemporal smoothing models to estimate recent (1 month) and long-term (7–14 years) exposures to PM2.5-10, and PM2.5 preceding base-line cognitive testing (1995–2001) of participants residing in the contiguous United States. We used generalized estimating equation regression to estimate differences in the rate of cognitive decline across levels of PM2.5-10 and PM2.5 exposures. The main outcome measure was cognition, via validated telephone assessments, administered 3 times at approximately 2-year intervals, including tests of general cognition, verbal memory, category fluency, working memory, and attention. Results Higher levels of long-term exposure to both PM2.5-10 and PM2.5 were associated with significantly faster cognitive decline. Two-year decline on a global score was 0.020 (95% CI, −0.032 to −0.008) standard units worse per 10 μg/m3 increment in PM2.5-10 exposure and 0.018 (95% CI, −0.035 to −0.002) units worse per 10 μg/m3 increment in PM2.5 exposure. These differences in cognitive trajectory were similar to those between women in our cohort who were approximately 2 years apart in age, indicating that the effect of a 10-μg/m3 increment in long-term PM exposure is cognitively equivalent to aging by approximately 2 years. Conclusion Long-term exposure to PM2.5-10 and PM2.5 at levels typically experienced by many individuals in the United States is associated with significantly worse cognitive

  5. Mixed neuropathologies and associations with domain-specific cognitive decline.

    PubMed

    Brenowitz, Willa D; Hubbard, Rebecca A; Keene, C Dirk; Hawes, Stephen E; Longstreth, W T; Woltjer, Randy L; Kukull, Walter A

    2017-09-22

    To test whether decline in specific cognitive domains associated with Alzheimer disease neuropathologic change (ADNC) is modified by co-occurrence of other neuropathologies such as Lewy body disease (LBD) or vascular brain injury (VBI). Data came from 1,603 autopsied participants evaluated at US Alzheimer's Disease Centers. Standardized z scores in memory, attention, language, and executive function were derived from neuropsychological test scores assessed at each annual visit. Multivariable linear mixed-effects models assessed associations between neuropathologies and longitudinal trajectories of domain scores. Compared to other participants, those with ADNC + LBD generally had worse cognitive trajectories, particularly lower initial executive function and faster attention decline. Participants with ADNC + VBI typically had less impairment and slower decline. Interactions were significant between LBD and ADNC for memory (p = 0.046) and between VBI and ADNC for language (p = 0.03); decline was slower than expected if these neuropathologies acted additively on the rate of decline. In secondary models, these interactions were limited to those with high ADNC (but not intermediate ADNC). In a subset of 260 participants with data on microinfarct location, cortical and subcortical microinfarcts were associated with decline in memory, language, and executive function in those without ADNC, but this effect was reduced among those with ADNC. ADNC + LBD (but not ADNC + VBI) was associated with poorer executive function and attention compared to other pathology groupings. However, the effect of co-occurring pathologies on cognitive trajectories may depend on the severity of ADNC. Future studies using antemortem biomarkers should seek to replicate these neuropathologic observations. © 2017 American Academy of Neurology.

  6. Dynamic hub load predicts cognitive decline after resective neurosurgery.

    PubMed

    Carbo, Ellen W S; Hillebrand, Arjan; van Dellen, Edwin; Tewarie, Prejaas; de Witt Hamer, Philip C; Baayen, Johannes C; Klein, Martin; Geurts, Jeroen J G; Reijneveld, Jaap C; Stam, Cornelis J; Douw, Linda

    2017-02-07

    Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of 'hub (over)load', caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning.

  7. Dynamic hub load predicts cognitive decline after resective neurosurgery

    PubMed Central

    Carbo, Ellen W. S.; Hillebrand, Arjan; van Dellen, Edwin; Tewarie, Prejaas; de Witt Hamer, Philip C.; Baayen, Johannes C.; Klein, Martin; Geurts, Jeroen J. G.; Reijneveld, Jaap C.; Stam, Cornelis J.; Douw, Linda

    2017-01-01

    Resective neurosurgery carries the risk of postoperative cognitive deterioration. The concept of ‘hub (over)load’, caused by (over)use of the most important brain regions, has been theoretically postulated in relation to symptomatology and neurological disease course, but lacks experimental confirmation. We investigated functional hub load and postsurgical cognitive deterioration in patients undergoing lesion resection. Patients (n = 28) underwent resting-state magnetoencephalography and neuropsychological assessments preoperatively and 1-year after lesion resection. We calculated stationary hub load score (SHub) indicating to what extent brain regions linked different subsystems; high SHub indicates larger processing pressure on hub regions. Dynamic hub load score (DHub) assessed its variability over time; low values, particularly in combination with high SHub values, indicate increased load, because of consistently high usage of hub regions. Hypothetically, increased SHub and decreased DHub relate to hub overload and thus poorer/deteriorating cognition. Between time points, deteriorating verbal memory performance correlated with decreasing upper alpha DHub. Moreover, preoperatively low DHub values accurately predicted declining verbal memory performance. In summary, dynamic hub load relates to cognitive functioning in patients undergoing lesion resection: postoperative cognitive decline can be tracked and even predicted using dynamic hub load, suggesting it may be used as a prognostic marker for tailored treatment planning. PMID:28169349

  8. Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice

    PubMed Central

    Feng, Xiaomei; Valdearcos, Martin; Uchida, Yosuke; Lutrin, David; Maze, Mervyn; Koliwad, Suneil K.

    2017-01-01

    Surgery can induce cognitive decline, a risk that increases with advancing age. In rodents, postoperative cognitive decline (POCD) is associated with the inflammatory activation of hippocampal microglia. To examine the role of microglia in POCD, we inhibited the colony-stimulating factor 1 receptor (CSF1R) in adult mice, effectively depleting CNS microglia. Surgical trauma (tibial fracture) reduced the ability of mice to remember a conditioned response learned preoperatively, a deficit more pronounced and persistent in mice with diet-induced obesity (DIO). Whereas microglial depletion by itself did not affect learning or memory, perioperative microglial depletion remarkably protected mice, including those with DIO, from POCD. This protection was associated with reduced hippocampal levels of inflammatory mediators, abrogation of hippocampal recruitment of CCR2+ leukocytes, and higher levels of circulating inflammation-resolving factors. Targeting microglia may thus be a viable strategy to mitigate the development of POCD, particularly in those with increased vulnerability. PMID:28405620

  9. Effect of APOE and CD33 on Cognitive Decline.

    PubMed

    Hayden, Kathleen M; Lutz, Michael W; Kuchibhatla, Maragatha; Germain, Cassandra; Plassman, Brenda L

    2015-01-01

    An Alzheimer's disease (AD) diagnosis is preceded by a long period of cognitive decline. We previously demonstrated increased risk of decline among individuals possessing one or more APOE ε4 alleles together with a family history of AD. The objective of this study is to investigate the possibility that such an increased risk might be due to AD risk genes with small effects in combination with APOE. Participants in the Health and Retirement Study (HRS) over the age of 65, who contributed DNA, and had two or more evaluations with an abbreviated version of the modified Telephone Interview for Cognitive Status (TICS-m) were eligible for the study (n = 7451). A genetic risk score (g-score) was derived using AD risk genes' meta-analyses data, assigning risk according to the number of risk alleles and summed over all the risk genes. Trajectories of cognitive function were modeled in four groups of Caucasian participants with and without one or more APOE ε4 alleles and either a high or low g-score: APOE ε4-/low g-score; APOE ε4-/high g-score; APOE ε4+/low g-score; and APOE ε4+/high g-score. Post hoc analyses evaluated interactions between individual genes and APOE. Individuals in the APOE ε4+/high g-score group exhibited the greatest cognitive decline over time (p<.0001). This risk appeared to be greater than the sum of the effects of either high g-score or APOE ε4 alone. When gene interactions were individually tested with APOE, a statistically significant interaction with CD33 was discovered (p = 0.04) although the interaction was no longer significant when adjusted for multiple comparisons. Individuals with multiple AD risk genes in addition to having one or more APOE ε4 alleles are at greater risk of cognitive decline than individuals with either APOE ε4 or a high genetic risk score. Among those with one or more APOE ε4 alleles, having one or more copies of the CD33 C (risk) allele may further increase the risk of cognitive decline.

  10. Chronic obstructive pulmonary disease. An original model of cognitive decline.

    PubMed

    Incalzi, R A; Gemma, A; Marra, C; Muzzolon, R; Capparella, O; Carbonin, P

    1993-08-01

    In order to characterize the neuropsychologic profile of patients with hypoxic-hypercapnic chronic obstructive pulmonary disease (COPD), the performance of 36 patients with COPD 69 +/- 10 yr of age (mean +/- SD) on 19 tests exploring eight cognitive domains was compared with those of 29 normal adults (69 +/- 7 yr of age), 20 normal elderly adults (78 +/- 2 yr of age), 26 patients with Alzheimer-type dementia (72 +/- 6 yr of age), and 28 with multi-infarct dementia (MID) (70 +/- 8 yr of age). The discriminant analysis of cognitive test scores showed that 48.5% of patients with COPD had a specific pattern of cognitive deterioration characterized by a dramatic impairment in verbal and verbal memory tasks, well-preserved visual attention, and diffuse worsening of the other functions. The remaining patients with COPD were functionally classified as normal adults (12.1%), normal elderly adults (15.2%), those with MID (12.1%), and those with Alzheimer-type dementia (12.1%) according to discriminant analysis. Cognitive impairment was significantly and positively correlated with age (p < 0.05) and duration of hypoxic-hypercapnic chronic respiratory failure (p < 0.05). Because patients with COPD were receiving oxygen therapy from the beginning of oxyhemoglobin desaturation, results suggest that continuous oxygen therapy does not prevent or only partly prevents cognitive decline in COPD. Although some analogies between age-related and COPD-related cognitive decline are evident, a distinct cognitive profile was found in a large fraction of patients with COPD and it differs in several aspects from those of both normal and demented subjects.

  11. Nutrition, the brain and cognitive decline: insights from epigenetics.

    PubMed

    Dauncey, M J

    2014-11-01

    Nutrition affects the brain throughout life, with profound implications for cognitive decline and dementia. These effects are mediated by changes in expression of multiple genes, and responses to nutrition are in turn affected by individual genetic variability. An important layer of regulation is provided by the epigenome: nutrition is one of the many epigenetic regulators that modify gene expression without changes in DNA sequence. Epigenetic mechanisms are central to brain development, structure and function, and include DNA methylation, histone modifications and non-protein-coding RNAs. They enable cell-specific and age-related gene expression. Although epigenetic events can be highly stable, they can also be reversible, highlighting a critical role for nutrition in prevention and treatment of disease. Moreover, they suggest key mechanisms by which nutrition is involved in the pathogenesis of age-related cognitive decline: many nutrients, foods and diets have both immediate and long-term effects on the epigenome, including energy status, that is, energy intake, physical activity, energy metabolism and related changes in body composition, and micronutrients involved in DNA methylation, for example, folate, vitamins B6 and B12, choline, methionine. Optimal brain function results from highly complex interactions between numerous genetic and environmental factors, including food intake, physical activity, age and stress. Future studies linking nutrition with advances in neuroscience, genomics and epigenomics should provide novel approaches to the prevention of cognitive decline, and treatment of dementia and Alzheimer's disease.

  12. Bilingualism and Cognitive Decline: A Story of Pride and Prejudice.

    PubMed

    Woumans, Evy; Versijpt, Jan; Sieben, Anne; Santens, Patrick; Duyck, Wouter

    2017-09-11

    In a recent review, Mukadam, Sommerlad, and Livingston (2017) argue that bilingualism offers no protection against cognitive decline. The authors examined the results of 13 studies (five prospective, eight retrospective) in which monolinguals and bilinguals were compared for cognitive decline and onset of dementia symptoms. Analysis of four of the five prospective studies resulted in the conclusion that there was no difference between monolinguals and bilinguals, whereas seven of the eight retrospective studies actually showed bilingualism to result in a four-to-five year delay of symptom onset. The authors decided to ignore the results from the retrospective studies in favor of those from the prospective studies, reasoning that the former may be confounded by participants' cultural background and education levels. In this commentary, we argue that most of these studies actually controlled for these two variables and still found a positive effect of bilingualism. Furthermore, we argue that the meta-analysis of the prospective studies is not complete, lacking the results of two crucial reports. We conclude that the literature offers substantial evidence for a bilingual effect on the development of cognitive decline and dementia.

  13. 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.

  14. Neuroanatomical substrates of age-related cognitive decline

    PubMed Central

    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 age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and DTI measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerned with measurement and methodology that may lead to stronger conclusions in the future. PMID:21463028

  15. Flavonol Intake and Cognitive Decline in Middle-Aged Adults.

    PubMed

    Root, Martin; Ravine, Erin; Harper, Anne

    2015-12-01

    Cognitive decline occurs with age and may be slowed by dietary measures, including increased intake of dietary phytochemicals. However, evidence from large and long-term studies of flavonol intake is limited. Dietary intakes of flavonols were assessed from a large biracial study of 10,041 subjects, aged 45-64, by analysis of a food frequency questionnaire administered at visit 1 of triennial visits. Cognitive function was assessed at visits 2 and 4 with the following three cognitive performance tests: the delayed word recall test, the revised Wechsler Adult Intelligence Scale digit symbol subtest, and the word fluency test of the Multilingual Aphasia Examination. The change in each score over 6 years was calculated, and a combined standardized change score was calculated. Generalized linear models controlled for age, ethnicity, gender, education level, energy intake, current smoking, physical activity, body mass index, diabetes, and vitamin C intake. Total flavonols across quintiles of intake were positively associated with preserved combined cognitive function (P<.001). This pattern with preserved combined cognitive function was consistent for the three major individual flavonols in the diet, myricetin, kaempferol, and quercetin (each P<.001). The positive association with total flavonols was strongest for the digit symbol subtest (P<.001). In this cohort, flavonol intake was correlated with protected cognitive function over time.

  16. Faith-based cognitive behavioral therapy: easing depression in the elderly with cognitive decline.

    PubMed

    Ceramidas, Dagmar M

    2012-01-01

    Minimizing depression in residential aged care facilities is a formidable challenge but doing so may improve quality of life and protect against dementia. A pilot project with residents with cognitive decline and concurrent depression tested the suitability of a faith-based cognitive behavioral therapy (CBT) intervention in reducing participant levels of depression, offering promising results.

  17. Space and location of cerebral microbleeds, cognitive decline, and dementia in the community.

    PubMed

    Ding, Jie; Sigurðsson, Sigurður; Jónsson, Pálmi V; Eiriksdottir, Gudny; Meirelles, Osorio; Kjartansson, Olafur; Lopez, Oscar L; van Buchem, Mark A; Gudnason, Vilmundur; Launer, Lenore J

    2017-05-30

    To assess the association of the number and anatomic location of cerebral microbleeds (CMBs), visible indicators of microvascular damage on MRI, with incident cognitive disease in the general population of older people. In the longitudinal population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, 2,602 participants 66 to 93 years of age and free of prevalent dementia underwent brain MRI and cognitive testing of verbal memory, processing speed, and executive function at baseline and a mean of 5.2 years later. Adjudicated incident dementia cases were diagnosed according to international guidelines. In the multiple linear regression models adjusted for demographic, genetic, cardiovascular risk, and other cerebrovascular MRI markers, the presence of CMBs located in deep or mixed (deep and lobar) areas was associated with a greater decline in all 3 cognitive domains. Mixed CMBs were the strongest correlate for decline in memory and speed. Compared to those with no CMBs, participants with ≥3 CMBs had a steeper decline in a composite measure of global cognitive function, memory, and speed. Among those with ≥3 deep or mixed CMBs, associations were strongest for memory; the association with speed was strongest in those having ≥3 strictly lobar CMBs. People with ≥3 CMBs, regardless of their locations, had a higher incidence of all-cause dementia and vascular dementia. Mixed or a higher load of CMBs, with some specificity for location, is associated with accelerated cognitive decline in older people. These findings suggest a role for hypertensive vasculopathy and the combined effect of hypertensive and cerebral amyloid angiopathy in the pathogenesis of cognitive deterioration. © 2017 American Academy of Neurology.

  18. 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.

  19. Relationship between regional atrophy rates and cognitive decline in mild cognitive impairment

    PubMed Central

    McDonald, Carrie R.; Gharapetian, Lusineh; McEvoy, Linda K.; Fennema-Notestine, Christine; Hagler, Donald J.; Holland, Dominic; Dale, Anders M.

    2010-01-01

    We investigated the relationship between regional atrophy rates and 2-year cognitive decline in a large cohort of patients with mild cognitive impairment (MCI; N=103) and healthy controls (N=90). Longitudinal MRIs were analyzed using high-throughput image analysis procedures. Atrophy rates were derived by calculating percent cortical volume loss between baseline and 24-month scans. Step-wise regressions were performed to investigate the contribution of atrophy rates to language, memory, and executive functioning decline, controlling for age, gender, baseline performances, and disease progression. In MCI, left temporal lobe atrophy rates were associated with naming decline, whereas bilateral temporal, left frontal, and left anterior cingulate atrophy rates were associated with semantic fluency decline. Left entorhinal atrophy rate was associated with memory decline and bilateral frontal atrophy rates were associated with executive function decline. These data provide evidence that regional atrophy rates in MCI contribute to domain-specific cognitive decline, which appears to be partially independent of disease progression. MRI measures of regional atrophy can provide valuable information for understanding the neural basis of cognitive impairment in MCI. PMID:20471718

  20. The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease.

    PubMed

    Begeti, Faye; Tan, Adrian Y K; Cummins, Gemma A; Collins, Lucy M; Guzman, Natalie Valle; Mason, Sarah L; Barker, Roger A

    2013-11-01

    Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington's disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke's Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington's disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington's disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington's disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington's disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington's disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.

  1. Citicoline, use in cognitive decline: vascular and degenerative.

    PubMed

    García-Cobos, Rocío; Frank-García, Ana; Gutiérrez-Fernández, María; Díez-Tejedor, Exuperio

    2010-12-15

    CDP-choline has been widespread used in humans for decades as a treatment for many types of cognitive impairment. Despite this, its mechanism of action still remains unclear, but several experimental models in acute cerebral ischaemia suggest that it could have a brain repair action. Due to the lack of significant adverse effects and its high tolerability, there has been a growing interest for this molecule in recent years. In this article, a review of the most significant published clinical trials in cognitive decline has been made. A few Citicoline trials have studied its effects at medium and long-term on vascular cognitive impairment and Alzheimer's disease. Results show that Citicoline seems to have beneficial impact on several cognitive domains, but the methodological heterogeneity of the these studies makes it difficult to draw conclusions about these effects. New trials with a greater number of patients, uniform diagnostic criteria for inclusion and standardized neuropsychological assessment are needed to evidence with much more consistency Citicoline efficacy upon cognitive disorders. The use of new neuroimaging procedures in current trials could be of great interest.

  2. Patterns of Cognitive Decline Prior to Dementia in Persons with Mild Cognitive Impairment

    PubMed Central

    Cloutier, Simon; Chertkow, Howard; Kergoat, Marie-Jeanne; Gauthier, Serge; Belleville, Sylvie

    2015-01-01

    Abstract Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer’s disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults. PMID:26401770

  3. Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline.

    PubMed

    McPhee, Grace M; Downey, Luke A; Noble, Anthony; Stough, Con

    2016-10-01

    As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens. Cognitive training has been shown to improve performance in some cognitive domains; including memory, processing speed, executive function and attention in older adults. These cognitive changes are thought to be related to improvements in brain connectivity and neural circuitry. Bacopa monnieri has also been shown to improve specific domains of cognition, sensitive to age associated cognitive decline (particularly processing speed and memory). These Bacopa monnieri dependent improvements may be due to the increase in specific neuro-molecular mechanisms implicated in the enhancement of neural connections in the brain (i.e. synaptogenesis). In particular, a number of animal studies have shown Bacopa monnieri consumption upregulates calcium dependent kinases in the synapse and post-synaptic cell, crucial for strengthening and growing connections between neurons. These effects have been shown to occur in areas important for cognitive processes, such as the hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that encourage synaptogenesis, while cognitive training enhances brain connectivity, Bacopa monnieri supplementation could theoretically enhance and strengthen synaptic changes acquired through cognitive training. Therefore, the current paper hypothesises that the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently, as an effective

  4. Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults

    PubMed Central

    Miller, Joshua W.; Harvey, Danielle J.; Beckett, Laurel A.; Green, Ralph; Farias, Sarah Tomaszewski; Reed, Bruce R.; Olichney, John M.; Mungas, Dan M.; DeCarli, Charles

    2016-01-01

    cognitively normal groups (16.2 [9.4] vs 20.0 [10.3] and 19.7 [13.1] ng/mL, respectively; P = .006). The mean (SD) follow-up was 4.8 (2.5) years. Rates of decline in episodic memory and executive function among VitD-deficient (episodic memory: β = −0.04 [SE = 0.02], P = .049; executive function: β = −0.05 [SE = 0.02], P = .01) and VitD-insufficient (episodic memory: β = −0.06 [SE = 0.02], P < .001; executive function: β = −0.04 [SE = 0.02], P = .008) participants were greater than those with adequate status after controlling for age, sex, education, ethnicity, body mass index, season of blood draw, vascular risk, and apolipoprotein E4 genotype. Vitamin D status was not significantly associated with decline in semantic memory or visuospatial ability. Exclusion of participants with dementia did not substantially affect the associations between VitD status and rates of cognitive decline. CONCLUSIONS AND RELEVANCE Low VitD status was associated with accelerated decline in cognitive function domains in ethnically diverse older adults, including African American and Hispanic individuals who exhibited a high prevalence of VitD insufficiency or deficiency. It remains to be determined whether VitD supplementation slows cognitive decline. PMID:26366714

  5. Association of Cerebral Microbleeds With Cognitive Decline and Dementia.

    PubMed

    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

    2016-08-01

    Cerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear. To determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population. The Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards. Cerebral microbleed presence, location, and number. Cognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia. In total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference

  6. Relationship between frailty and cognitive decline in older Mexican Americans.

    PubMed

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

    2008-10-01

    To examine the association between frailty status and change in cognitive function over time in older Mexican Americans. Data used were from the Hispanic Established Population for the Epidemiological Study of the Elderly. Five southwestern states: Texas, New Mexico, Colorado, Arizona, and California. One thousand three hundred seventy noninstitutionalized Mexican-American men and women aged 65 and older with a Mini-Mental State Examination (MMSE) score of 21 or higher at baseline (1995/96). Frailty, defined as three or more of the following components: unintentional weight loss of more than 10 pounds, weakness (lowest 20% in grip strength), self-reported exhaustion, slow walking speed (lowest 20% in 16-foot walk time in seconds), and low physical activity level (lowest 20% on Physical Activity Scale for the Elderly score). Information about sociodemographic factors, MMSE score, medical conditions (stroke, heart attack, diabetes mellitus, arthritis, cancer, and hypertension), depressive symptoms, and visual impairment was obtained. Of the 1,370 subjects, 684 (49.9%) were not frail, 626 (45.7%) were prefrail (1-2 components), and 60 (4.4%) were frail (>/=3 components) in 1995/96. Using general linear mixed models, it was found that frail subjects had greater cognitive decline over 10 years than not frail subjects (estimate=-0.67, standard error=0.13; P<.001). This association remained statistically significant after controlling for potential confounding factors. Frail status in older Mexican Americans with MMSE scores of 21 or higher at baseline is an independent predictor of MMSE score decline over a 10-year period. Future research is needed to establish pathophysiological components that can clarify the relationship between frailty and cognitive decline.

  7. The preclinical Alzheimer cognitive composite: measuring amyloid-related decline.

    PubMed

    Donohue, Michael C; Sperling, Reisa A; Salmon, David P; Rentz, Dorene M; Raman, Rema; Thomas, Ronald G; Weiner, Michael; Aisen, Paul S

    2014-08-01

    As Alzheimer disease (AD) research moves to intervene in presymptomatic phases of the disease, we must develop outcome measures sensitive to the earliest disease-related changes. To demonstrate the feasibility of a cognitive composite outcome for clinically normal elderly participants with evidence of AD pathology using the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC). The ADCS-PACC combines tests that assess episodic memory, timed executive function, and global cognition. The ADCS-PACC is the primary outcome measure for the first clinical trial in preclinical AD (ie, the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study). With the ADCS-PACC, we derive pilot estimates of amyloid-related decline using data from 2 observational studies conducted in North America and another conducted in Australia. The participants analyzed had normal cognition and mean ages of 75.81, 71.37, and 79.42 years across the 3 studies. For the 2 studies that collected data on Aβ levels (ADNI and AIBL), we estimate decline in a preclinical AD "Aβ-positive" placebo group and compare them with an "Aβ-negative" group. For the study that did not include data on Aβ levels (the ADCS Prevention Instrument [ADCS-PI] study), we grouped participants by the presence of APOE-ε4 and by clinical progression. In ADNI, Aβ-positive participants showed more decline than did Aβ-negative participants with regard to the ADCS-PACC score at 24 months (mean [SE] difference, -1.239 [0.522] [95% CI, -2.263 to -0.215]; P = .02). In AIBL, the mean (SE) difference is significant at both 18 months (-1.009 [0.406] [95% CI, -1.805 to -0.213]; P = .01) and 36 months (-1.404 [0.452] [95% CI, -2.290 to -0.519]; P = .002). In the ADCS-PI study, APOE-ε4 allele carriers performed significantly worse on the ADCS-PACC at 24 months (mean [SE] score, -0.742 [0.294] [95% CI, -1.318 to -0.165]; P = .01) and 36 months (-1.531 [0.469] [95% CI, -2.450 to -0.612]; P = .001). In the ADCS

  8. Cognitive predictors of functional decline in vascular dementia

    PubMed Central

    Jefferson, Angela L.; Cahn-Weiner, Deborah; Boyle, Patricia; Paul, Robert H.; Moser, David J.; Gordon, Norman; Cohen, Ronald A.

    2009-01-01

    SUMMARY Background This study examined changes in cognitive-functional relationships in vascular dementia (VaD) over the course of one year. Methods Twenty-four patients with probable VaD were administered the Dementia Rating Scale (DRS). Caregivers completed an informant-based measure of instrumental (IADL) and basic activities of daily living (BADL). Follow-up assessment was conducted one-year post-baseline. Results Logistic regression revealed that changes in the DRS Initiation/Perseveration and DRS Memory subscales were significantly associated with declines in IADLs and BADLs, respectively. Conclusions Among patients with VaD, longitudinal changes in IADLs and BADLs are most strongly associated with changes in executive functioning and memory abilities, respectively. Findings suggest that different cognitive functions subserve complex instrumental and rote, habituated basic functional activities, and neuropsychological screening measures are useful in the prediction of such functional changes. PMID:16906630

  9. Reversal of cognitive decline: A novel therapeutic program

    PubMed Central

    Bredesen, Dale E.

    2014-01-01

    This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

  10. Cerebral Microbleeds, CSF p-Tau, and Cognitive Decline: Significance of Anatomic Distribution.

    PubMed

    Chiang, G C; Cruz Hernandez, J C; Kantarci, K; Jack, C R; Weiner, M W

    2015-09-01

    Cerebral microbleeds are associated with aging, hypertension, and Alzheimer disease. Microbleeds in a lobar distribution are believed to reflect underlying amyloid angiopathy, whereas microbleeds in the deep gray matter and infratentorial brain are commonly seen with hypertension. However, it is unknown how microbleeds in either distribution are related to Alzheimer pathogenesis. The purpose of this analysis was to test whether lobar and deep gray/infratentorial microbleeds demonstrate differential associations with CSF amyloid-β and phosphorylated tau 181 protein levels and longitudinal cognitive decline. A total of 626 subjects (151 cognitively normal, 389 with mild cognitive impairment, and 86 with Alzheimer disease) from the Alzheimer's Disease Neuroimaging Initiative who had undergone 3T MR imaging and lumbar puncture were included in the analysis. The number and location of microbleeds were assessed visually. Associations between lobar or deep gray/infratentorial microbleeds with CSF amyloid-β levels, abnormal CSF phosphorylated tau 181 protein levels, and longitudinal cognitive decline were assessed by using ordinary least-squares, logistic, and mixed-effects regression models while adjusting for covariates. Having ≥3 lobar microbleeds was associated with lower levels of CSF amyloid-β (P = .001). After adjusting for CSF amyloid-β level, lobar microbleeds were independently associated with a higher likelihood of having an abnormal CSF phosphorylated tau 181 protein level (P = .004). Lobar microbleeds were associated with accelerated longitudinal cognitive decline (P = .007). Deep gray/infratentorial microbleeds revealed no significant associations. The distribution of microbleeds revealed different associations with amyloid-β and phosphorylated tau 181 protein levels and cognition. Lobar and deep gray/infratentorial microbleeds should be considered separately with regard to Alzheimer disease pathogenesis. © 2015 by American Journal of Neuroradiology.

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

    PubMed Central

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

    2016-01-01

    Background. 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. Methods. 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. Results. 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). Conclusions. 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. PMID:27448678

  12. [Characteristic of the cognitive evoked potentials at elderly people with cognitive decline].

    PubMed

    Deryabina, I N; Dzhos, Yu S

    2017-01-01

    Results of research of cognitive visual evoked potentials at elderly women with various level of cognitive decline are shown in article. Both relevance of the early diagnostics of cognitive disorders and expedience of using of methods of functional neurovisualization to reveal higher cortical dysfunctions are shown also. To appraise cognitive functions we applied express-method of evaluating of cognitive functions during normal aging. According to results of this test two groups were created: the 1st - women without cognitive disorders, the 2nd - with mild cognitive impairment. The evoked potentials were registered for all participants with using of 128-channel system GES-300. Latency of P300-wave and reaction time were calculated. According to temporary characteristics of P300-wave it has been revealed that the group with cognitive decline differed in longer latent period in centro-temporo-parietal area of the left hemisphere, and also longer reaction time. However, latency of P300 in central-parietal areas of the right hemisphere was less than one at persons of the control group. These changes reflect dysfunction of structures of a medial temporal lobe which is expressed mainly by the memory disorders.

  13. Sleep duration, cognitive decline, and dementia risk in older women

    PubMed Central

    Chen, Jiu-Chiuan; Espeland, Mark A.; Brunner, Robert L.; Lovato, Laura C.; Wallace, Robert B.; Leng, Xiaoyan; Phillips, Lawrence S.; Robinson, Jennifer G.; Kotchen, Jane M.; Johnson, Karen C.; Manson, JoAnn E.; Stefanick, Marcia L.; Sarto, Gloria E.; Mysiw, W. Jerry

    2015-01-01

    Background Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. Methods We conducted a prospective study on 7444 community-dwelling women (aged 65–80) with self-reported sleep duration, within the Women’s Health Initiative Memory Study in 1995–2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. Results We found a statistically significant (p=0.03) V-shaped association, with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs.7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. Conclusion In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. PMID:26086180

  14. Cognitive decline before the age of 50 can be detected with sensitive cognitive measures.

    PubMed

    Ferreira, Daniel; Correia, Rut; Nieto, Antonieta; Machado, Alejandra; Molina, Yaiza; Barroso, José

    2015-01-01

    To define the profile of age-related differences in cognition in healthy middle-aged adults in order to identify the most sensitive measures of early cognitive decline. To study whether these differences precede cognitive decline in the elderly. 141 cognitively normal participants (101 middle-aged adults with age 40-50±2; and 40 elderly individuals with age 65±2) were assessed with a comprehensive neuropsychological protocol covering processing speed, attention, executive functions, verbal and visual episodic memory, procedural memory, visuoconstructive, visuoperceptive and visuospatial functions, and language. Age-related differences were detected before the age of 50 in cognitive reaction time, executive control, initial learning in verbal episodic memory, complex visuoconstructive and visuospatial functions, and lexical access. These differences preceded more extensive cognitive decline present at the age of 65. Our findings suggest subtle executive dysfunction before the age of 50, together with slowing in processing speed later on in the transition to old age. This profile could be explained by changes in the frontal lobe and its connections, starting at middle-age. These findings, together with future research, may be important for the diagnosis, prognosis, and prevention of pathological aging at a very early level.

  15. Cognitive Stimulation and Cognitive and Functional Decline in Alzheimer's Disease: The Cache County Dementia Progression Study

    PubMed Central

    Treiber, Katherine A.; Carlson, Michelle C.; Corcoran, Chris; Norton, Maria C.; Breitner, John C. S.; Piercy, Kathleen W.; DeBerard, Michael Scott; Stein, David; Foley, Beth; Welsh-Bohmer, Kathleen A.; Frye, Amber; Lyketsos, Constantine G.

    2011-01-01

    Objectives. To examine the association of engagement in cognitively stimulating activities with cognitive and functional decline in a population-based sample of incident Alzheimer's disease (AD). Method. After diagnosis, 187 participants (65% females) were followed semiannually for a mean 2.7 (SD = 0.4) years. Mean age and education were 84.6 (SD = 5.8) and 13.2 (SD = 2.9) years. Caregivers enumerated cognitively stimulating leisure activities via the Lifestyle Activities Questionnaire. Cognition was assessed using the Mini-Mental State Examination and functional ability via the Clinical Dementia Rating sum of boxes. Linear mixed models tested the association between stimulating activities and change over time in each outcome. Covariates were demographic factors, estimated premorbid IQ, presence/absence of the APOE ϵ4 allele, duration of dementia, level of physical activity, and general health. Results. At initial assessment, 87% of participants were engaged in one or more stimulating activities, with mean (SD) activities = 4.0 (3.0). This number declined to 2.4 (2.0) at the final visit. There was a statistical interaction between dementia duration and number of activities in predicting rate of cognitive decline (p = .02) and overall functional ability (p = .006). Discussion. Active involvement in cognitively stimulating pursuits may be beneficial for persons with AD. PMID:21441386

  16. Clinical and Subclinical Macrovascular Disease as Predictors of Cognitive Decline in Older Patients With Type 2 Diabetes

    PubMed Central

    Feinkohl, Insa; Keller, Marketa; Robertson, Christine M.; Morling, Joanne R.; Williamson, Rachel M.; Nee, Lisa D.; McLachlan, Stela; Sattar, Naveed; Welsh, Paul; Reynolds, Rebecca M.; Russ, Tom C.; Deary, Ian J.; Strachan, Mark W.J.; Price, Jackie F.

    2013-01-01

    OBJECTIVE Macrovascular disease may contribute to increased risk of accelerated cognitive decline in patients with type 2 diabetes. We aimed to determine associations of measures of macrovascular disease with cognitive change in a cognitively healthy older population with type 2 diabetes. RESEARCH DESIGN AND METHODS Eight hundred thirty-one men and women (aged 60–75 years) attended two waves of the prospective Edinburgh Type 2 Diabetes Study (ET2DS). At baseline, clinical and subclinical macrovascular disease was measured, including cardiovascular event history, carotid intima-media thickness (cIMT), ankle brachial index (ABI), and serum N-terminal probrain natriuretic peptide (NT-proBNP). Seven neuropsychological tests were administered at baseline and after 4 years; scores were combined to a standardized general ability factor (g). Adjustment of follow-up g for baseline g assessed 4-year cognitive change. Adjustment for vocabulary (estimated premorbid ability) was used to estimate lifetime cognitive change. RESULTS Measures of cognitive decline were significantly associated with stroke, NT-proBNP, ABI, and cIMT, but not with nonstroke vascular events. The association of stroke with increased estimated lifetime cognitive decline (standardized β, −0.12) and of subclinical markers with actual 4-year decline (standardized β, −0.12, 0.12, and −0.15 for NT-proBNP, ABI, and cIMT, respectively) reached the Bonferroni-adjusted level of statistical significance (P < 0.006). Results altered only slightly on adjustment for vascular risk factors. CONCLUSIONS Stroke and subclinical markers of cardiac stress and generalized atherosclerosis are associated with cognitive decline in older patients with type 2 diabetes. Further investigation into the potential use of subclinical vascular disease markers in predicting cognitive decline is warranted. PMID:23579182

  17. From mild cognitive impairment to subjective cognitive decline: conceptual and methodological evolution

    PubMed Central

    Cheng, Yu-Wen; Chen, Ta-Fu; Chiu, Ming-Jang

    2017-01-01

    Identification of subjects at the early stages of Alzheimer’s disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%–17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features. PMID:28243102

  18. From mild cognitive impairment to subjective cognitive decline: conceptual and methodological evolution.

    PubMed

    Cheng, Yu-Wen; Chen, Ta-Fu; Chiu, Ming-Jang

    2017-01-01

    Identification of subjects at the early stages of Alzheimer's disease (AD) is fundamental for drug development and possible intervention or prevention of cognitive decline. The concept of mild cognitive impairment (MCI) evolved during the past two decades to define subjects at the transitional stage between normal aging and dementia. Evidence from cross-sectional and longitudinal studies has shown that MCI is associated with an increased risk of positive AD biomarkers and an increased annual conversion rate of 5%-17% to AD. The presence of AD biomarkers in subjects with MCI was associated with an even higher risk of progression to dementia. However, earlier clinical trials for pharmacotherapy in subjects with MCI were disappointing. To extend the spectrum of AD to an earlier stage before MCI, subjective cognitive decline (SCD) was introduced and was defined as self-reported cognitive decline before the deficits could be detected by cognitive tests. Subjects with SCD have an increased risk of underlying AD pathology. However, SCD can also develop secondary to other heterogeneous etiologies, including other neurodegenerative and psychiatric diseases, personality traits, physical conditions, and medication use. Several clinical and biomarker features were proposed to predict risk of conversion to AD in subjects with SCD. Further longitudinal studies are needed to support the validity of these high-risk features.

  19. The Cognitive Reserve Hypothesis: A Longitudinal Examination of Age-Associated Declines in Reasoning and Processing Speed

    PubMed Central

    Tucker-Drob, Elliot M.; Johnson, Kathy E.; Jones, Richard N.

    2009-01-01

    The term cognitive reserve is frequently used to refer to the ubiquitous finding that, during later life, those higher in experiential resources (e.g. education, knowledge) exhibit higher levels of cognitive function. This observation may be the result of either (1) experiential resources playing protective roles with respect to the cognitive declines associated with aging or (2) the persistence of differences in functioning that have existed since earlier adulthood. These possibilities were examined by applying accelerated longitudinal structural equation (growth curve) models to 5 year reasoning and speed data from the no-contact control group (N=690, 65 to 89 years of age at baseline) of the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) study. Vocabulary knowledge and years of education, as markers of cognitive reserve, were related to levels of cognitive functioning, but unrelated to rates of cognitive change, both before and after the (negative) relations between levels and rates were controlled for. These results suggest that cognitive reserve reflects the persistence of earlier differences in cognitive functioning rather than differential rates of age-associated cognitive declines. PMID:19271829

  20. The cognitive reserve hypothesis: a longitudinal examination of age-associated declines in reasoning and processing speed.

    PubMed

    Tucker-Drob, Elliot M; Johnson, Kathy E; Jones, Richard N

    2009-03-01

    The term cognitive reserve is frequently used to refer to the ubiquitous finding that, during later life, those higher in experiential resources (e.g., education, knowledge) exhibit higher levels of cognitive function. This observation may be the result of either experiential resources playing protective roles with respect to the cognitive declines associated with aging or the persistence of differences in functioning that have existed since earlier adulthood. These possibilities were examined by applying accelerated longitudinal structural equation (growth curve) models to 5-year reasoning and speed data from the no-contact control group (N = 690; age 65-89 years at baseline) of the Advanced Cognitive Training for Independent and Vital Elderly study. Vocabulary knowledge and years of education, as markers of cognitive reserve, were related to levels of cognitive functioning but unrelated to rates of cognitive change, both before and after the (negative) relations between levels and rates were controlled for. These results suggest that cognitive reserve reflects the persistence of earlier differences in cognitive functioning rather than differential rates of age-associated cognitive declines.

  1. Factors of Rapid Cognitive Decline in Late Onset Alzheimer's Disease.

    PubMed

    Koskas, Pierre; Henry-Feugeas, Marie Cecile; Feugeas, Jean-Paul; Ou, Phalla; Drunat, Olivier

    2017-01-01

    Rapid Cognitive Decline (RCD) in Alzheimer's Disease (AD) is associated with a worse disease progression. There is no consensual predictor of RCD and only a few studies have focused on RCD in late-onset dementia, the most common form of AD. To identify the predictors of RCD, in a population of community-dwelling patients with recently diagnosed late onset AD. Community-dwelling subjects aged >75 consulting for the first time in Old Age Memory outpatient center from 2009 to 2012 were considered. All patients underwent a standardized clinical dementia investigation. Patients were classified as rapid decliners when they demonstrated a loss of 3 points or greater in MMSE during the first six months. 130 patients were included (42 males, 88 females, mean ages 82.7±4.58). The average baseline MMSE score was 23.36±3.78. In regression analysis, the Free Recall Scores, categorical fluency scores were the most highly predictive of RCD. These results are important for the design of clinical trials and also, in clinical practice, for both physicians and families in planning long-term care. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Antihypertensive withdrawal for the prevention of cognitive decline.

    PubMed

    Jongstra, Susan; Harrison, Jennifer K; Quinn, Terry J; Richard, Edo

    2016-11-01

    Clinical trials and observational data have variously shown a protective, harmful or neutral effect of antihypertensives on cognitive function. In theory, withdrawal of antihypertensives could improve cerebral perfusion and reduce or delay cognitive decline. However, it is also plausible that withdrawal of antihypertensives may have a detrimental effect on cognition through increased incidence of stroke or other vascular events. To assess the effects of complete withdrawal of at least one antihypertensive medication on incidence of dementia, cognitive function, blood pressure and other safety outcomes in cognitively intact and cognitive impaired adults. We searched ALOIS, the specialised register of the Cochrane Dementia and Cognitive Improvement Group, with additional searches conducted in MEDLINE, Embase, PsycINFO, CINAHL, LILACS, Web of Science Core Collection, ClinicalTrials.gov and the World Health Organization Portal/ICTRP on 12 December 2015. There were no language or date restrictions applied to the electronic searches, and no methodological filters were used to restrict the search. We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) provided they compared withdrawal of antihypertensive medications with continuation of the medications and included an outcome measure assessing cognitive function or a clinical diagnosis of dementia. We included studies with healthy participants, but we also included studies with participants with all grades of severity of existing dementia or cognitive impairment. Two review authors examined titles and abstracts of citations identified by the search for eligibility, retrieving full texts where needed to identify studies for inclusion, with any disagreement resolved by involvement of a third author. Data were extracted independently on primary and secondary outcomes. We used standard methodological procedures expected by Cochrane.The primary outcome measures of interest were changes in global

  3. Multivariable network associated with cognitive decline and dementia.

    PubMed

    Licastro, Federico; Porcellini, Elisa; Chiappelli, Martina; Forti, Paola; Buscema, Massimo; Ravaglia, Giovanni; Grossi, Enzo

    2010-02-01

    Data mining of a large data base from the population longitudinal study named "The Conselice Study" has been the focus of the present investigation. Initially, 65 years old or older participants were interviewed, underwent medical and cognitive examination, and were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 35 genetic and/or phenotypic factors with incident cognitive decline and dementia were investigated. The new mathematical approach, called the Auto Contractive Map (AutoCM), was able to show the differential importance of each variables. This new variable processing created a semantic connectivity map that: (a) preserved non-linear associations; (b) showed connection schemes; (c) captured the complex dynamics of adaptive interactions. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Few variables resulted to be aggregation points and were considered as major biological hubs. Three hubs were identified in the hydroxyl-methyl-gutaryl-CoA reductase (HMGCR) enzyme, plasma cholesterol levels and age. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. This data analysis method was compared with another mathematical model called mutual information relevance network and results are presented and discussed.

  4. Inflammation-associated declines in cerebral vasoreactivity and cognition in type 2 diabetes.

    PubMed

    Chung, Chen-Chih; Pimentel, Daniela; Jor'dan, Azizah J; Hao, Ying; Milberg, William; Novak, Vera

    2015-08-04

    The aim of this prospective study was to investigate the relationships between inflammation, cerebral vasoregulation, and cognitive decline in type 2 diabetes mellitus (T2DM) over a 2-year span. Sixty-five participants (aged 66 ± 9.2 years, 35 with T2DM, 33 women) were enrolled for this 2-year prospective study. Continuous arterial spin labeling at 3-tesla MRI was used to measure global and regional cerebral perfusion and vasoreactivity. Neuropsychological measures were evaluated at the beginning and completion of the study. The associations between serum inflammatory markers, regional cerebral vasoreactivity, and cognitive functions were examined using least squares models. After 2 years of follow-up, participants with T2DM had diminished global and regional cerebral vasoreactivity and a decline in multiple cognitive tasks compared with baseline (p < 0.0001-0.012). In the T2DM group, lower cerebral vasoreactivity was associated with a greater decrease in daily living activities score (r(2) adj = 0.35, p = 0.04), and lower global vasodilation was associated with a greater decline in executive function (r(2) adj = 0.6, p = 0.047). Higher serum soluble intercellular and vascular adhesion molecules, higher cortisol, and higher C-reactive protein levels at baseline were associated with greater decreases in cerebral vasoreactivity and vasodilation only in the T2DM group (r(2) adj = 0.16-0.53, p = 0.007-0.048), independent of diabetes control and 24-hour blood pressure. Higher glycated hemoglobin A1c levels were associated with a greater increase in vasoconstriction in the T2DM group. Inflammation may further impair cerebral vasoregulation, which consequently accelerates decline in executive function and daily activities performance in older people with T2DM. © 2015 American Academy of Neurology.

  5. 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

    2017-03-06

    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

  6. Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory

    PubMed Central

    Davey, Adam; Elias, Merrill F.; Robbins, Michael A.; Seliger, Stephen L.; Dore, Gregory A.

    2013-01-01

    Background Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. Methods We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). Results Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b = 0.21SD decline per unit ln(eGFR), 95% CI: 0.04–0.38, P = .018], verbal episodic memory [b = 0.28 SD decline per unit ln(eGFR), 95% CI: 0.02–0.54, P = 0.038] and abstract reasoning [b = 0.36 SD decline per unit ln(eGFR), 95% CI: 0.04–0.67, P = 0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. Conclusions Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline. PMID

  7. Does cognitive decline decrease health utility value in older adult patients with cancer?

    PubMed

    Akechi, Tatsuo; Aiki, Sayo; Sugano, Koji; Uchida, Megumi; Yamada, Atsuro; Komatsu, Hirokazu; Ishida, Takashi; Kusumoto, Shigeru; Iida, Shinsuke; Okuyama, Toru

    2017-05-01

    Cognitive decline is common among older adults with cancer. The present study aimed to investigate the impact of cognitive decline on health utility value in older adults suffering from cancer. Consecutive patients aged 65 years or older with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Patients were asked to complete the EuroQoL-5 (EQ-5D) scale to measure health utility and the Mini-Mental State Examination to assess cognitive decline. The potential impact of cognitive decline was investigated with univariate analysis. A multivariate regression analysis was conducted to control for potential confounding factors. Complete data were obtained from 87 patients, 29% of whom had cognitive decline. The mean ± SE EQ-5D score for patients with cognitive decline was significantly lower than that for those without cognitive decline (0.67 ± 0.04 vs 0.79 ± 0.03, t = 2.38, P = 0.02). However, multiple regression analysis showed that cognitive decline was not significantly associated with EQ-5D scores. Female sex and lower performance scores (worse physical condition) were significantly associated with EQ-5D scores. Cognitive decline may be involved in decreased health utility value in older adult patients with cancer. However, this effect does not seem to be independent, and the patient's physical condition may be a relevant confounding factor. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

  8. Sleep disturbances and cognitive decline in the Northern Manhattan Study.

    PubMed

    Ramos, Alberto R; Gardener, Hannah; Rundek, Tatjana; Elkind, Mitchell S V; Boden-Albala, Bernadette; Dong, Chuanhui; Cheung, Ying Kuen; Stern, Yaakov; Sacco, Ralph L; Wright, Clinton B

    2016-10-04

    To examine frequent snoring, sleepiness, and sleep duration with baseline and longitudinal performance on neuropsychological (NP) battery. The analysis consists of 711 participants of the Northern Manhattan Study (NOMAS) with sleep data and NP assessment (age 63 ± 8 years, 62% women, 18% white, 17% black, 67% Hispanic) and 687 with repeat NP testing (at a mean of 6 ± 2 years). The main exposures were snoring, sleepiness, and sleep duration obtained during annual follow-up. Using factor analysis-derived domain-specific Z scores for episodic memory, language, executive function, and processing speed, we constructed multivariable regression models to evaluate sleep symptoms with baseline NP performance and change in performance in each NP domain. In the cross-sectional analysis, adjusting for demographics and the NOMAS vascular risk score, participants with frequent snoring had worse executive function (β = -12; p = 0.04) and processing speed (β = -13; p = 0.02), but no difference in with episodic memory or language. Those with severe daytime sleepiness (β = -26; p = 0.009) had worse executive function, but no changes in the other NP domains. There was no cross-sectional association between sleep duration and NP performance. Frequent snoring (β = -29; p = 0.0007), severe daytime sleepiness (β = -29; p = 0.05), and long sleep duration (β = -29; p = 0.04) predicted decline in executive function, adjusting for demographic characteristics and NOMAS vascular risk score. Sleep symptoms did not explain change in episodic memory, language, or processing speed. In this race-ethnically diverse community-based cohort, sleep symptoms led to worse cognitive performance and predicted decline in executive function. © 2016 American Academy of Neurology.

  9. Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline.

    PubMed

    Gooding, Amanda L; Choi, Jimmy; Fiszdon, Joanna M; Wilkins, Kirsten; Kirwin, Paul D; van Dyck, Christopher H; Devanand, Davangere; Bell, Morris D; Rivera Mindt, Monica

    2016-10-01

    Cognitive rehabilitation for mild cognitive impairment (MCI) and early Alzheimer's disease is readily available to the geriatric population. Initial evidence suggests that techniques incorporating motivational strategies to enhance treatment engagement may provide more benefit than computerised training alone. Seventy four adults with subclinical cognitive decline were randomly assigned to computerised cognitive training (CCT), Cognitive Vitality Training (CVT), or an Active Control Group (ACG), and underwent neuropsychological evaluations at baseline and four-month follow-up. Significant differences were found in changes in performance on the Modified Mini Mental State Examination (mMMSE) and measures of verbal learning and memory across treatment groups. Experimental groups showed greater preservation of functioning on the mMMSE than the ACG group, the CVT group performed better than the ACG group on one measure of verbal learning and both measures of verbal memory, and the CCT group performed better than the ACG group on one measure of verbal learning and one measure of verbal memory. There were no significant group differences between the CVT and CCT groups on measures of verbal learning or memory. It was concluded that computerised cognitive training may offer the most benefit when incorporated into a therapeutic milieu rather than administered alone, although both appear superior to more generic forms of cognitive stimulation.

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

    PubMed Central

    Yu, Lei; Boyle, Patricia A.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

    2016-01-01

    Objectives: We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults. Methods: 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. Results: 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. Conclusions: Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline. PMID:26819457

  11. 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.

  12. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

    PubMed Central

    Latimer, Caitlin S.; Brewer, Lawrence D.; Searcy, James L.; Chen, Kuey-Chu; Popović, Jelena; Kraner, Susan D.; Thibault, Olivier; Blalock, Eric M.; Landfield, Philip W.; Porter, Nada M.

    2014-01-01

    Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues, including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5–6 mo, middle-aged F344 rats were fed diets containing low, medium (typical amount), or high (100, 1,000, or 10,000 international units/kg diet, respectively) vitamin D3, and hippocampal-dependent learning and memory were then tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication, and G protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced, corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function, and they suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging. PMID:25267625

  13. Oxidative stress and aberrant signaling in aging and cognitive decline

    PubMed Central

    Dröge, Wulf; Schipper, Hyman M

    2007-01-01

    Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of reactive oxygen species (ROS) as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation. Oxidative conditions cause not only structural damage but also changes in the set points of redox-sensitive signaling processes including the insulin receptor signaling pathway. In the absence of insulin, the otherwise low insulin receptor signaling is strongly enhanced by oxidative conditions. Autophagic proteolysis and sirtuin activity, in turn, are downregulated by the insulin signaling pathway, and impaired autophagic activity has been associated with neurodegeneration. In genetic studies, impairment of insulin receptor signaling causes spectacular lifespan extension in nematodes, fruit flies, and mice. The predicted effects of age-related oxidative stress on sirtuins and autophagic activity and the corresponding effects of antioxidants remain to be tested experimentally. However, several correlates of aging have been shown to be ameliorated by antioxidants. Oxidative damage to mitochondrial DNA and the electron transport chain, perturbations in brain iron and calcium homeostasis, and changes in plasma cysteine homeostasis may altogether represent causes and consequences of increased oxidative stress. Aging and cognitive decline thus appear to involve changes at multiple nodes within a complex regulatory network. PMID:17517043

  14. Life space and risk of Alzheimer disease, mild cognitive impairment, and cognitive decline in old age.

    PubMed

    James, Bryan D; Boyle, Patricia A; Buchman, Aron S; Barnes, Lisa L; Bennett, David A

    2011-11-01

    To test the hypothesis that a constricted life space, the extent of movement through the environment covered during daily functioning, is associated with increased risk of incident Alzheimer disease (AD), increased risk of mild cognitive impairment (MCI), and more rapid cognitive decline in older adults. Two prospective cohort studies. Retirement communities, community-based organizations, churches, and senior subsidized housing facilities across the Chicago metropolitan area. A total of 1,294 community-dwelling elders without baseline clinical dementia. Detailed annual clinical evaluation to diagnose incident AD and MCI, and document change in cognitive function. During a mean (SD) follow-up of 4.4 (1.7) years, 180 persons developed AD. In a proportional hazards model controlling for age, sex, race, and education, a more constricted life space was associated with an increased risk of AD (hazard ratio = 1.21, confidence interval: 1.08-1.36). A person with a life space constricted to their home was almost twice as likely to develop AD than a person with the largest life space (out of town). The association did not vary along demographic lines and persisted after the addition of terms for performance-based physical function, disability, depressive symptoms, social network size, vascular disease burden, and vascular risk factors. The association remained consistent after excluding persons with MCI at baseline and who developed AD in the first 2 years of observation. A constricted life space was also associated with an increased risk of MCI (hazard ratio = 1.17, confidence interval: 1.06-1.28), and a more rapid rate of global cognitive decline (estimate: -0.012, standard error: 0.003, t[5033] = -3.58, p <0.001). A constricted life space is associated with increased risk of AD, MCI, and cognitive decline among older persons.

  15. A random change point model for cognitive decline in Alzheimer’s disease and mild cognitive impairment

    PubMed Central

    Yu, Lei; Boyle, Patricia; Wilson, Robert S.; Segawa, Eisuke; Leurgans, Sue; De Jager, Philip L.; Bennett, David A.

    2012-01-01

    Background We present a random change point model to characterize decline in cognition among community-based elderly who developed Alzheimer’s disease (AD) or amnestic mild cognitive impairment (MCI), and to examine how decline varies with age, sex, education, and APOE status. Methods Using longitudinal cohort data on cognitive function, we fit a piecewise linear trajectory with a random change point that allows different rates of cognitive decline before and after the change point. We estimated the change point that signals the onset of cognitive impairment, and examined the association of risk factors with the location of the change point as well as the rates of decline before and after the change point. Results Among participants who were dementia free at enrollment and developed incident AD, the change point occurred on average 5.7 years after enrollment and the rate of cognitive decline after the change point nearly quadrupled. Age, education, and APOE status play important but different roles in the timing of the onset of cognitive impairment and in the rates of decline before and after its onset. Results were similar among participants who were cognitively unimpaired at enrollment but later developed amnestic MCI or AD. Conclusions The random change point model provides a more comprehensive understanding of the relation of risk factors with the onset of cognitive impairment and rates of decline before and after its onset. PMID:22814083

  16. A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.

    PubMed

    Dacks, Penny A; Armstrong, Joshua J; Brannan, Stephen K; Carman, Aaron J; Green, Allan M; Kirkman, M Sue; Krakoff, Lawrence R; Kuller, Lewis H; Launer, Lenore J; Lovestone, Simon; Merikle, Elizabeth; Neumann, Peter J; Rockwood, Kenneth; Shineman, Diana W; Stefanacci, Richard G; Velentgas, Priscilla; Viswanathan, Anand; Whitmer, Rachel A; Williamson, Jeff D; Fillit, Howard M

    2016-08-20

    Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.

  17. The Dietary Approaches to Stop Hypertension Diet, Cognitive Function, and Cognitive Decline in American Older Women.

    PubMed

    Berendsen, Agnes A M; Kang, Jae H; van de Rest, Ondine; Feskens, Edith J M; de Groot, Lisette C P G M; Grodstein, Francine

    2017-05-01

    To examine the association between long-term adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with cognitive function and decline in older American women. Prospective cohort study. The Nurses' Health Study, a cohort of registered nurses residing in 11 US states. A total of 16,144 women from the Nurses' Health Study, aged ≥70 years, who underwent cognitive testing a total of 4 times by telephone from 1995 to 2001 (baseline), with multiple dietary assessments between 1984 and the first cognitive examination. DASH adherence for each individual was based on scoring of intakes of 9 nutrient or food components. Long-term DASH adherence was calculated as the average DASH adherence score from up to 5 repeated measures of diet. Primary outcomes were cognitive function calculated as the average scores of the 4 repeated measures, as well as cognitive change of the Telephone Interview for Cognitive Status score and composite scores of global cognition and verbal memory. Greater adherence to long-term DASH score was associated with better average cognitive function, irrespective of apolipoprotein E ε4 allele status [multivariable-adjusted differences in mean z-scores between extreme DASH quintiles = 0.04 (95% confidence interval, CI 0.01-0.07), P trend = .009 for global cognition; 0.04 (95% CI 0.01-0.07), P trend = .002 for verbal memory and 0.16 (95% CI 0.03-0.29), and P trend = .03 for Telephone Interview for Cognitive Status, P interaction >0.24]. These differences were equivalent to being 1 year younger in age. Adherence to the DASH score was not associated with change in cognitive function over 6 years. Our findings in the largest cohort on dietary patterns and cognitive function to date indicate that long-term adherence to the DASH diet is important to maintain cognitive function at older ages. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.

  18. Decline in changing Montreal Cognitive Assessment (MoCA) scores is associated with post-stroke cognitive decline determined by a formal neuropsychological evaluation

    PubMed Central

    Teoh, Hock Luen; Chan, Bernard Poon-Lap; Seet, Raymond Chee Seong; Venketasubramanian, Narayanaswarmy; Sharma, Vijay Kumar; Chen, Christopher Li-Hsian; Dong, YanHong

    2017-01-01

    Objectives We aimed to examine changes in the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) scores within a one-year period after stroke/transient ischemic attack (TIA) in associating cognitive decline determined by a formal neuropsychological test battery. Methods Patients with ischemic stroke/TIA received MoCA and MMSE at baseline within 14 days after stroke/TIA, at 3–6 months and 1-year follow-ups. The scores of MoCA and MMSE were considered to have declined if there were a reduction of ≥2 points in the respective scores measured across two time points. The decline in neuropsychological diagnosis transitional status was defined by a category transition from no cognitive impairment or any cognitive impairment to a more severe cognitive impairment or dementia. Results 275 patients with a mean age of 59.8 ± 11.6 years, and education of 7.7 ± 4.3 years completed all the assessments at baseline, 3–6 months and 1-year follow-ups. A decline in MoCA scores from 3–6 months to 1 year was associated with higher risk of decline in diagnosis transitional status (odd ratio = 3.21, p = 0.004) in the same time period whereas there was no association with a decline in MMSE scores. Conclusions The decline in MoCA scores from 3–6 months to 1 year after stroke/TIA has three times higher risk for decline in the diagnosis transitional status. The decline of MoCA scores (reduction ≥ 2points) is associated with the decline in neuropsychological diagnosis transitional status. PMID:28346532

  19. Hospitalization and cognitive decline: Can the nature of the relationship be deciphered?

    PubMed

    Mathews, Sarah B; Arnold, Steven E; Epperson, C Neill

    2014-05-01

    Evidence for a relationship between hospitalization and incident cognitive decline exists mainly in the literature focusing on critical care hospitalization. Recent studies, however, have also found an association between noncritical care hospitalization and the development of cognitive decline. This article will review the literature pertaining to hospitalization and cognitive decline, including hospitalizations for both critical and noncritical care, and in medical and surgical patients. The article will also explore the various factors that have been implicated in the development of cognitive decline and dementia. Review of the literature was completed using PubMed and Medline search programs. Several articles supporting evidence for the association between hospitalization and cognitive decline are available. Evidence for potential mediating factors also does exist. There is evidence to support an association between hospitalization and development of cognitive decline. Factors that could mediate this association include, but may not be limited to, delirium, medications, stress, and depression. There is a need for further research in this area in order to better understand the underlying pathophysiology involved in the development of cognitive decline and dementia and to determine if preventive measures might be beneficial in decreasing risk for cognitive decline for patients who are hospitalized. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  20. The potential effects of meditation on age-related cognitive decline: a systematic review.

    PubMed

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  1. The potential effects of meditation on age-related cognitive decline: a systematic review

    PubMed Central

    Gard, Tim; Hölzel, Britta K.; Lazar, Sara W.

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182

  2. The Roles of Exercise and Yoga in Ameliorating Depression as a Risk Factor for Cognitive Decline

    PubMed Central

    Rosenbaum, Simon

    2016-01-01

    Currently, there are no effective pharmaceutical treatments to reduce cognitive decline or prevent dementia. At the same time, the global population is aging, and rates of dementia and mild cognitive impairment (MCI) are on the rise. As such, there is an increasing interest in complementary and alternative interventions to treat or reduce the risk of cognitive decline. Depression is one potentially modifiable risk factor for cognitive decline and dementia. Notably, exercise and yoga are two interventions known to both reduce symptoms of depression and improve cognitive function. The current review discusses the efficacy of exercise and yoga to ameliorate depression and thereby reduce the risk of cognitive decline and potentially prevent dementia. Potential mechanisms of change, treatment implications, and future directions are discussed. PMID:28044084

  3. Walking ability to predict future cognitive decline in old adults: A scoping review.

    PubMed

    Kikkert, Lisette H J; Vuillerme, Nicolas; van Campen, Jos P; Hortobágyi, Tibor; Lamoth, Claudine J

    2016-05-01

    Early identification of individuals at risk for cognitive decline may facilitate the selection of those who benefit most from interventions. Current models predicting cognitive decline include neuropsychological and/or biological markers. Additional markers based on walking ability might improve accuracy and specificity of these models because motor and cognitive functions share neuroanatomical structures and psychological processes. We reviewed the relationship between walking ability at one point of (mid) life and cognitive decline at follow-up. A systematic literature search identified 20 longitudinal studies. The average follow-up time was 4.5 years. Gait speed quantified walking ability in most studies (n=18). Additional gait measures (n=4) were step frequency, variability and step-length. Despite methodological weaknesses, results revealed that gait slowing (0.68-1.1 m/sec) preceded cognitive decline and the presence of dementia syndromes (maximal odds and hazard ratios of 10.4 and 11.1, respectively). The results indicate that measures of walking ability could serve as additional markers to predict cognitive decline. However, gait speed alone might lack specificity. We recommend gait analysis, including dynamic gait parameters, in clinical evaluations of patients with suspected cognitive decline. Future studies should focus on examining the specificity and accuracy of various gait characteristics to predict future cognitive decline.

  4. Does type 2 diabetes increase rate of cognitive decline in older Mexican Americans?

    PubMed Central

    Mayeda, Elizabeth R.; Haan, Mary N.; Yaffe, Kristine; Kanaya, Alka M.; Neuhaus, John

    2014-01-01

    Estimating effects of diabetes on cognitive change among older Mexican Americans is important, yet challenging because diabetes and cognitive decline both predict mortality, which can induce survival bias. Older Mexican Americans in the Sacramento Area Latino Study on Aging (n=1,634) completed Modified Mini-Mental State Exams (3MSE) and diabetes assessments up to seven times (1998-2007). We examined baseline and new onset diabetes and cognitive decline with joint longitudinal-survival models to account for death. At baseline, 32.4% of participants had diabetes and 15.8% developed diabetes during the study. Over the study, 22.8% of participants died. In joint longitudinal-survival models, those with baseline diabetes experienced faster cognitive decline (p=0.003) and higher mortality (HR=1.88, 95% CI 1.48-2.38) than those without diabetes. Cognitive decline and mortality were similar for those with new onset diabetes and those without diabetes. For a typical person, 3MSE scores declined by 2.3 points among those without diabetes and 4.3 points among those with baseline diabetes during the last 6 years of study. Ignoring the impact of death yielded a 17.0% smaller estimate of the effect of baseline diabetes on cognitive decline. Analyses that overlook the association between cognitive decline and mortality may underestimate the effect of diabetes on cognitive aging. PMID:25650694

  5. Decline in Memory, Visuospatial Ability, and Crystalized Cognitive Abilities in Older Adults: Normative Aging or Terminal Decline?

    PubMed

    Bendayan, R; Piccinin, A M; Hofer, S M; Cadar, D; Johansson, B; Muniz-Terrera, G

    2017-01-01

    The aim of this study is to explore the pattern of change in multiple measures of cognitive abilities in a sample of oldest-old adults, comparing two different time metrics (chronological age and time to death) and therefore examining both underlying conceptual assumptions (age-related change and terminal decline). Moreover, the association with individual characteristics as sex, education, and dementia diagnosis was also examined. Measures of cognitive status (Mini-Mental State Examination and the Swedish Clock Test) and tests of crystallized (knowledge and synonyms), memory (verbal memory, nonverbal long-term memory, recognition and correspondence, and short-term memory), and visuospatial ability were included. The sample consisted of 671 older Swedish adult participants of the OCTO Twin Study. Linear mixed models with random coefficients were used to analyse change patterns and BIC indexes were used to compare models. Results showed that the time to death model was the best option in analyses of change in all the cognitive measures considered (except for the Information Test). A significant cognitive decline over time was found for all variables. Individuals diagnosed with dementia had lower scores at the study entrance and a faster decline. More educated individuals performed better in all the measures of cognition at study entry than those with poorer education, but no differences were found in the rate of change. Differences were found in age, sex, or time to death at baseline across the different measures. These results support the terminal decline hypothesis when compared to models assuming that cognitive changes are driven by normative aging processes.

  6. No association of the variant rs11887120 in DNMT3A with cognitive decline in individuals with mild cognitive impairment.

    PubMed

    Bey, Katharina; Wolfsgruber, Steffen; Karaca, Ilker; Wagner, Holger; Lardenoije, Roy; Becker, Julian; Milz, Esther; Kornhuber, Johannes; Peters, Oliver; Frölich, Lutz; Hüll, Michael; Rüther, Eckart; Wiltfang, Jens; Riedel-Heller, Steffi; Scherer, Martin; Jessen, Frank; Maier, Wolfgang; van den Hove, Daniel L; Rutten, Bart Pf; Wagner, Michael; Ramirez, Alfredo

    2016-05-01

    Alterations in DNA methylation have been associated with cognitive decline and Alzheimer's disease. A recent study of mild cognitive impairment (MCI) reported a significant association between annual decline in cognitive function and the rs11887120 SNP located in DNMT3A, a gene implicated in DNA methylation. Here, we aimed to replicate this finding in two independent MCI cohorts (n = 1024); however, no significant association was observed in either cohort or the pooled dataset. In stratified analyses for conversion to Alzheimer's disease status, no association between rs11887120 and cognitive decline was observed in either converters or nonconverters. In conclusion, our analyses provide no support for the hypothesis that genetic variants in DNMT3A are implicated in cognitive performance decline in individuals with MCI.

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

    PubMed Central

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

    2014-01-01

    Background 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. Objective 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). Methods 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). Results 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). Conclusion 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. PMID

  8. Plasma EGF and cognitive decline in Parkinson's disease and Alzheimer's disease.

    PubMed

    Lim, Nicholas S; Swanson, Christine R; Cherng, Hua-Ren; Unger, Travis L; Xie, Sharon X; Weintraub, Daniel; Marek, Ken; Stern, Matthew B; Siderowf, Andrew; Trojanowski, John Q; Chen-Plotkin, Alice S

    2016-05-01

    Cognitive decline occurs in multiple neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Shared underlying mechanisms may exist and manifest as shared biomarker signatures. Previously, we nominated plasma epidermal growth factor (EGF) as a biomarker predicting cognitive decline in patients with established PD. Here, we investigate EGF as a predictive biomarker in prodromal PD, as well as AD. A cohort of PD patients (n = 236) was recruited to replicate our finding that low baseline EGF levels predict future cognitive decline. Additionally, plasma EGF and cognitive outcome measures were obtained from individuals with normal cognition (NC, n = 58), amnestic mild cognitive impairment (AD-MCI, n = 396), and Alzheimer's disease (AD, n = 112) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to investigate whether low EGF levels correlate with cognitive status and outcome in AD-MCI and AD. Third, plasma EGF and cognitive measures were evaluated in the high-risk asymptomatic Parkinson's Associated Risk Study (PARS) cohort (n = 165) to investigate the association of EGF and cognitive performance in a PD prodromal context. In both PD and AD-MCI, low baseline plasma EGF predicted poorer long-term cognitive outcomes. In asymptomatic individuals at highest risk for developing PD from the PARS cohort, low baseline plasma EGF associated with poorer performance in the visuospatial domain but not in other cognitive domains. Low plasma EGF at baseline predicts cognitive decline in both AD and PD. Evidence for this signal may exist in prodromal stages of both diseases.

  9. 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

  10. 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.

  11. Memory Complaints and Cognitive Decline: Data from the GUIDAGE Study1.

    PubMed

    Dardenne, Sophie; Delrieu, Julien; Sourdet, Sandrine; Cantet, Christelle; Andrieu, Sandrine; Mathiex-Fortunet, Hélène; Fougère, Bertrand; Vellas, Bruno

    2017-10-03

    Subjective cognitive decline (SCD) may be a very early symptom of Alzheimer's disease (AD) and may be associated with a cognitive decline in a cognitively normal population. The McNair and Kahn Scale was used to assess memory complaints in the GuidAge study. Our objectives were to examine if the McNair and Kahn Scale can predict cognitive decline and to screen which (if any) of the question(s) of this scale would better predict this cognitive decline. The GuidAge study was a phase III, multicenter, randomized, double blind, placebo-controlled study. Individuals aged 70 years and older, without cognitive impairment (Clinical Dementia Rate (CDR = 0)) at baseline who had spontaneously reported SCD were included in this study. The 20-item version of the McNair and Kahn Scale was used to assess SCD and a standardized neuropsychological assessment was used to assess the cognitive status. 1,307 patients with SCD and with CDR = 0 at baseline were included. During the 5 years of follow-up, 519 patients showed cognitive decline. Incidence of aggravation score of CDR was 13.40% person years (95% CI [12.24-14.56]). Results showed a significant relationship between the McNair and Kahn Scale score and decline in cognitive performance (HR 1.012; 95% CI [1.002-1.021]; p = 0.0156). Among the 20 items, 5 were statistically significant to predict cognitive decline after adjustment. SCD is a promising indicator of memory impairment. Our study found that using the McNair and Kahn scale can predict cognitive decline. A 5-item version of this scale could be used to screen patients in clinical practice and in clinical research.

  12. Gait Speed and Grip Strength Reflect Cognitive Impairment and Are Modestly Related to Incident Cognitive Decline in Memory Clinic Patients With Subjective Cognitive Decline and Mild Cognitive Impairment: Findings From the 4C Study.

    PubMed

    Hooghiemstra, Astrid M; Ramakers, Inez H G B; Sistermans, Nicole; Pijnenburg, Yolande A L; Aalten, Pauline; Hamel, Renske E G; Melis, René J F; Verhey, Frans R J; Olde Rikkert, Marcel G M; Scheltens, Philip; van der Flier, Wiesje M

    2017-06-01

    Prospective studies in the general population show that slow gait speed is associated with cognitive decline and clinical progression to dementia. However, longitudinal studies in memory clinic populations are mostly lacking. We aimed to study the association between gait speed and grip strength and cognitive functioning at baseline and cognitive decline over time in memory clinic patients with subjective cognitive decline and mild cognitive impairment. We included 309 patients (age 70 ± 9 years, 108 [35%] women, Mini-Mental State Examination 27 ± 3 points). Baseline gait speed was assessed over 15 feet, grip strength with a hydraulic hand dynamometer. Cognitive functioning was assessed annually with a comprehensive test battery during 3 years. Age- and gender-adjusted linear mixed models showed that slower gait speed was related to worse baseline attention, memory, information processing speed, and verbal fluency. Longitudinally, gait speed was related to decline in information processing speed and executive functioning. Weaker grip strength was related to worse baseline information processing speed and executive functioning but there were no longitudinal associations. Cox proportional hazards models revealed no significant associations with clinical progression. Our findings suggest that markers of physical performance are related to current cognitive status and modestly related to cognitive decline but are seemingly not useful as an early marker of incident clinical progression.

  13. Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons.

    PubMed

    Donohue, Michael C; Sperling, Reisa A; Petersen, Ronald; Sun, Chung-Kai; Weiner, Michael W; Aisen, Paul S

    2017-06-13

    Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline. To characterize and quantify the risk for Alzheimer-related cognitive decline among cognitively normal individuals with elevated brain amyloid. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal individuals in the United States and Canada. Participants were observed from August 23, 2005, to June 7, 2016, for a median of 3.1 years (interquartile range, 2.0-4.2 years; maximum follow-up, 10.3 years) as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Individuals were classified at baseline as having normal (n = 243) or elevated (n = 202) brain amyloid using positron emission tomography amyloid imaging or a cerebrospinal fluid assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC; a sum of 4 baseline standardized z scores, which decreases with worse performance), Mini-Mental State Examination (MMSE; 0 [worst] to 30 [best] points), Clinical Dementia Rating Sum of Boxes (CDR-Sum of Boxes; 0 [best] to 18 [worst] points), and Logical Memory Delayed Recall (0 [worst] to 25 [best] story units). Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women. The mean score for PACC at baseline was 0.00 (2.60); for MMSE, 29.0 (1.2); for CDR-Sum of Boxes, 0.04 (0.14); and for Logical Memory Delayed Recall, 13.1 (3.3). Compared with the group with normal amyloid, those with elevated amyloid had worse mean scores at 4 years on the PACC (mean difference, 1.51 points [95% CI, 0.94-2.10]; P < .001), MMSE (mean difference, 0.56 points [95% CI, 0.32-0.80]; P < .001), and CDR-Sum of Boxes (mean difference, 0.23 points [95

  14. 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.

  15. Effects of Diabetes Mellitus on Cognitive Decline in Patients with Alzheimer Disease: A Systematic Review.

    PubMed

    Li, Jun; Cesari, Matteo; Liu, Fei; Dong, Birong; Vellas, Bruno

    2017-02-01

    Basic and clinical research support a link between diabetes mellitus and Alzheimer disease (AD). However, the relationship with AD progression is unclear. This review focuses on the association between diabetes and cognitive decline in patients with AD. The literature published through May 2015 was searched in 3 databases: PubMed, Embase and Cochrane. Studies evaluating the effects of diabetes on patients with AD or cognitive decline were included, and extracted data were analyzed. A total of 10 articles met the inclusion criteria for review. The results of these studies were inconsistent in terms of the association between diabetes and cognitive decline. Only 2 studies demonstrated that the presence of diabetes was independently related to the progression of cognitive decline in the patients with AD, and 3 studies suggested that histories of diabetes were not correlated with the changes in cognitive function in patients with AD. Half of the included studies even indicated that histories of diabetes were associated with lesser declines in cognitive function in patients with AD. Current evidence indicates that the link between diabetes and cognitive decline in patients with AD is uncertain. Further clinical studies are needed, with larger samples, long-term follow up and an extended battery of cognitive assessments.

  16. Personality and Cognitive Decline in Older Adults: Data From a Longitudinal Sample and Meta-Analysis.

    PubMed

    Luchetti, Martina; Terracciano, Antonio; Stephan, Yannick; Sutin, Angelina R

    2016-07-01

    Personality traits are associated with risk of dementia; less is known about their association with the trajectory of cognitive functioning. This research examines the association between the 5 major dimensions of personality and cognitive function and decline in older adulthood and includes a meta-analysis of published studies. Personality traits, objective and subjective memory, and cognitive status were collected in a large national sample (N = 13,987) with a 4-year follow-up period. For each trait, the meta-analysis pooled results from up to 5 prospective studies to examine personality and change in global cognition. Higher Neuroticism was associated with worse performance on all cognitive measures and greater decline in memory, whereas higher Conscientiousness and Openness were associated with better memory performance concurrently and less decline over time. All traits were associated with subjective memory. Higher Conscientiousness and lower Extraversion were associated with better cognitive status and less decline. Although modest, these associations were generally larger than that of hypertension, diabetes, history of psychological treatment, obesity, smoking, and physical inactivity. The meta-analysis supported the association between Neuroticism and Conscientiousness and cognitive decline. Personality is associated with cognitive decline in older adults, with effects comparable to established clinical and lifestyle risk factors. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. 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.

  18. Handgrip strength as a means of monitoring progression of cognitive decline - A scoping review.

    PubMed

    Fritz, Nora E; McCarthy, Caitlin J; Adamo, Diane E

    2017-05-01

    Cognitive decline in older adults contributes to reduced ability to perform daily tasks and continued disuse leads to muscle weakness and potentiates functional loss. Despite explicit links between the motor and cognitive systems, few health care providers assess motor function when addressing the needs of individuals with cognitive loss. Early and easy measurable biomarkers of cognitive decline have the potential to improve care for individuals with dementia and mild cognitive impairment. The aim of this study was to conduct a systematic search to determine the relationship among handgrip strength, as a measure of global muscle strength, and cognitive decline over time. Fifteen prospective, cohort, longitudinal studies of adults >60years old who were healthy or at risk of cognitive decline at study onset were included in the review. Studies that investigated changes in cognition relative to baseline grip strength and, those that investigated changes in grip strength relative to cognitive function were revealed. Findings here support the use of handgrip strength as a way to monitor cognitive changes and show that reduced handgrip strength over time may serve as a predictor of cognitive loss with advancing age. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Decline of cognition in multiple sclerosis: dissociable deficits.

    PubMed Central

    Jennekens-Schinkel, A; Sanders, E A

    1986-01-01

    Three female patients (ages 32, 37 and 27 years) developed progressive deficits of cognition in stages of multiple sclerosis in which physical disability ratings were low. Neuropsychological examination revealed severe cognitive impairments in the first two patients. Cognitive functioning was essentially intact in the third patient, although her work pace was significantly slowed. CT scanning of the brain showed cortical atrophy as well as white matter lesions in patients 1 and 2, and multiple lesions and oedema of predominantly white matter in patient 3. The differences of cognitive dysfunction between the third and the first two patients may be related to involvement of different anatomical structures. Images PMID:3806111

  20. 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.

  1. Interactive effect of APOE genotype and blood pressure on cognitive decline: the PATH through life study.

    PubMed

    Andrews, Shea; Das, Debjani; Anstey, Kaarin J; Easteal, Simon

    2015-01-01

    The apolipoprotein E (APOE) *ε4 allele and hypertension are two of the most prevalent risk factors for cognitive decline in later life. Here we investigate whether cognitive decline is affected by interaction between these two risk factors. Specifically, we examine whether APOE*ε4 moderates the association between high blood pressure and cognition in later life. Cognitive function was assessed at three time points over a period of 8 years in 1,474 cognitively normal, community-dwelling adults aged 60-64 years at baseline. Blood pressure and APOE genotype were assessed at baseline. Blood pressure was measured categorically as 'Hypertension' and continuously as 'Mean Arterial Pressure' (MAP). Multilevel models were used to investigate main and interactive effects of APOE genotype and both hypertension and MAP on the rate of change of episodic memory, working memory, verbal ability, perceptual speed, and global cognition. The APOE-hypertension interaction was associated with a small but statistically significant increase in the rate of decline of episodic memory, verbal ability, and global cognition. However, its inclusion in the model did not increase the amount of outcome variation explained beyond that already explained by the effect of time. In contrast, the APOE-MAP interaction had no effect on the rate of decline in any of these domains of cognitive performance. These results provide tentative evidence that APOE genotype moderates the association between high blood pressure and cognitive decline in later life.

  2. 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.

  3. 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

  4. 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…

  5. 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…

  6. 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

    2016-08-19

    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.

  7. Neuropsychological Practice Effects in the Context of Cognitive Decline: Contributions from Learning and Task Novelty.

    PubMed

    Thorgusen, Sommer R; Suchy, Yana; Chelune, Gordon J; Baucom, Brian R

    2016-04-01

    Although cognitive decline is typically associated with decreasing practice effects (PEs) (presumably due to declining memory), some studies show increased PEs with declines in cognition. One explanation for these inconsistencies is that PEs reflect not only memory, but also rebounds from adapting to task novelty (i.e., novelty effect), leading to increased PEs. We examined a theoretical model of relationships among novelty effects, memory, cognitive decline, and within-session PEs. Sixty-six older adults ranging from normal to severely impaired completed measures of memory, novelty effects, and two trials each of Wechsler Adult Intelligence Scale, 4 th Edition Symbol Search and Coding. Interrelationships among variables were examined using regression analyses. PEs for Symbol Search and Coding (a) were related to different proposed PE components (i.e., memory and novelty effects), such that novelty effect predicted Symbol Search PE (R2 =.239, p<.001) and memory predicted Coding PE (R2 =.089, p=.015), and (b) showed different patterns across stages of cognitive decline, such that the greatest cognitive decline was associated with smallest Coding PE (R2 =.125, p=.004), whereas intermediate cognitive decline was associated with the greatest Symbol Search PE (R2 =.097, p=.040). The relationship between cognitive decline and PE for Symbol Search was partially mediated by novelty effect among older adults with abnormal cognitive decline (model R2 =.286, p<.001). These findings (a) suggest that PE is not a unitary construct, (b) offer an explanation for contradictory findings in the literature, and (c) highlight the need for a better understanding of component processes of PE across different neuropsychological measures.

  8. Neurodegenerative Properties of Chronic Pain: Cognitive Decline in Patients with Chronic Pancreatitis

    PubMed Central

    Souren, Pierre; Arns, Martijn; Gordon, Evian; Vissers, Kris; Wilder-Smith, Oliver; van Rijn, Clementina M.; van Goor, Harry

    2011-01-01

    Chronic pain has been associated with impaired cognitive function. We examined cognitive performance in patients with severe chronic pancreatitis pain. We explored the following factors for their contribution to observed cognitive deficits: pain duration, comorbidity (depression, sleep disturbance), use of opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with severe pain due to chronic pancreatitis were determined using an extensive neuropsychological test battery. Data from three cognitive domains (psychomotor performance, memory, executive functions) were compared to data from healthy controls matched for age, gender and education. Multivariate multilevel analysis of the data showed decreased test scores in patients with chronic pancreatitis pain in different cognitive domains. Psychomotor performance and executive functions showed the most prominent decline. Interestingly, pain duration appeared to be the strongest predictor for observed cognitive decline. Depressive symptoms, sleep disturbance, opioid use and history of alcohol abuse provided additional explanations for the observed cognitive decline in some of the tests, but to a lesser extent than pain duration. The negative effect of pain duration on cognitive performance is compatible with the theory of neurodegenerative properties of chronic pain. Therefore, early and effective therapeutic interventions might reduce or prevent decline in cognitive performance, thereby improving outcomes and quality of life in these patients. PMID:21876748

  9. [Factors Associated with Cognitive Decline in a Population Less than 65 Years Old. A Systematic Review].

    PubMed

    Aguirre-Acevedo, Daniel Camilo; Henao, Eliana; Tirado, Victoria; Muñoz, Claudia; Giraldo Arango, Diana; Lopera Restrepo, Francisco; Jaimes Barragán, Fabián

    2014-01-01

    Cognitive decline could begin 20 years before the diagnosis of dementia. Besides age, several factors related to medical, socioeconomic, and behavioral and genetic condition may be associated with cognitive decline. The aim of this systematic review was to summarize evidence on the risk and protective factors for cognitive decline in people under 65 years old. A systematic review was conducted using a search strategy in MEDLINE and Embase, including longitudinal studies to analyze the effect of protective or risk factors on cognitive decline in a population under 65 years old. A total of 22 studies were included in this review. Factors such as diabetes, hyperinsulinemia, overweight or obesity, metabolic syndrome, education, physical activity, cognitive stimulation, marital status and diet, could be related to cognitive decline before 65 years of age. Cardiovascular risk factors and lifestyle conditions may be associated with cognitive decline before 65 years of age. However, the quality of the evidence was low. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  10. A randomized controlled trial of dietetic interventions to prevent cognitive decline in old age hostel residents.

    PubMed

    Kwok, T C Y; Lam, L C W; Sea, M M M; Goggins, W; Woo, J

    2012-10-01

    To examine whether dietary interventions promote intakes of fruit, vegetable, fish and lower salt intake were effective in preventing cognitive decline in older people. Dietary factors have been associated with cognitive function in older people. A total of 429 non-demented subjects in 14 old age hostels, with an average age of 83 years, were randomly assigned by hostel to have either regular group dietary counselling and menu changes or advice on hostel menu only. Food and salt intakes were estimated at regular intervals by 24-h recall or food record and fasting urinary sodium, respectively. The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale score. Secondary clinical outcomes were mini mental state examination, category fluency test, body weight, blood pressures and health-related quality of life. At baseline, the intervention group had more men and lower fish intake. When compared with control group, the intervention group had significantly less decline in intakes of fruit and fish. At month 33%, 22.2% and 27.2% of intervention and control group subjects had cognitive decline, respectively (Unadjusted P=0.285, χ² test). There were no significant group changes in secondary clinical outcomes. On subgroup analysis, fewer cognitively normal subjects in intervention group had cognitive decline at month 24 (adjusted P=0.065). Dietary interventions in older people were effective in maintaining fruit and fish intake, but this did not lead to a significant reduction in cognitive decline.

  11. Central Obesity, Leptin and Cognitive Decline: the Sacramento Area Latino Study on Aging

    PubMed Central

    Al Hazzouri, Adina Zeki; Haan, Mary N.; Whitmer, Rachel A.; Yaffe, Kristine; Neuhaus, John

    2012-01-01

    Background/Aims 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. Methods We analyzed 1480 dementia-free older Mexican-Americans who were followed over ten years. Cognitive function was assessed every 12 to 15 months with the Modified Mini Mental State Exam (3MSE) and the Spanish and English Verbal Learning Test (SEVLT). Results For females with small waist circumference (≤35inches), an interquartile range (IQR) difference in leptin was associated with 35% less 3MSE errors and 22% less decline in SEVLT score over 10 years. For males with small waist circumference (≤40inches), an IQR difference in leptin was associated with 44% less 3MSE errors and 30% less decline in SEVLT score over 10 years. There was no association between leptin and cognitive decline among females or males with large waist circumference. Conclusion Leptin interacts with central obesity in shaping cognitive decline. Our findings provide valuable information about the effects of metabolic risk factors on cognitive function. PMID:22814127

  12. Effects of early-life adversity on cognitive decline in older African Americans and whites.

    PubMed

    Barnes, Lisa L; Wilson, Robert S; Everson-Rose, Susan A; Hayward, Mark D; Evans, Denis A; Mendes de Leon, Carlos F

    2012-12-11

    Early-life adversity is related to adult health in old age but little is known about its relation with cognitive decline. Participants included more than 6,100 older residents (mean age = 74.9 [7.1] years; 61.8% African American) enrolled in the Chicago Health and Aging Project, a geographically defined, population-based study of risk factors for Alzheimer disease. Participants were interviewed at approximately 3-year intervals for up to 16 years. The interview included a baseline evaluation of early-life adversity, and administration of 4 brief cognitive function tests to assess change in cognitive function. We estimated the relation of early-life adversity to rate of cognitive decline in a series of mixed-effects models. In models stratified by race, and adjusted for age and sex, early-life adversity was differentially related to decline in African Americans and whites. Whereas no measure of early-life adversity related to cognitive decline in whites, both food deprivation and being thinner than average in early life were associated with a slower rate of cognitive decline in African Americans. The relations were not mediated by years of education and persisted after adjustment for cardiovascular factors. Markers of early-life adversity had an unexpected protective effect on cognitive decline in African Americans.

  13. Foreign language training as cognitive therapy for age-related cognitive decline: a hypothesis for future research.

    PubMed

    Antoniou, Mark; Gunasekera, Geshri M; Wong, Patrick C M

    2013-12-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline-Alzheimer's disease and other dementias-hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis.

  14. FDG-PET and CSF phospho-tau for prediction of cognitive decline in mild cognitive impairment.

    PubMed

    Fellgiebel, Andreas; Scheurich, Armin; Bartenstein, Peter; Müller, Matthias J

    2007-07-15

    Specific patterns of cortical glucose metabolism disturbances and increased CSF phospho-tau (p-tau(181)) concentrations could be demonstrated to predict cognitive decline and shift to dementia in amnestic mild cognitive impairment (MCI). But comparisons of both diagnostic tools have not been undertaken so far. The aim of the study was to compare (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) findings and CSF phospho-tau (p-tau(181)) measurements in the prediction of cognitive deterioration and conversion to dementia in MCI. During follow-up (mean 19 months) eight of 16 patients (50%) showed progressive cognitive decline, and four patients shifted to dementia. Pathological FDG-PET and elevated p-tau(181) levels both predicted deterioration. While p-tau(181) was highly sensitive for cognitive decline, FDG-PET was superior in predicting conversion to clinical dementia in MCI patients.

  15. Post-Concussion Cognitive Declines and Symptomatology Are Not Related to Concussion Biomechanics in High School Football Players

    PubMed Central

    Eckner, James T.; Surma, Tyler; Kutcher, Jeffrey S.

    2011-01-01

    Abstract Concussion is a major public health concern with nearly 4 million injuries occurring each year in the United States. In the acute post-injury stage, concussed individuals demonstrate cognitive function and motor control declines as well as reporting increased symptoms. Researchers have hypothesized that the severity of these impairments is related to impact magnitude. Using the Head Impact Telemetry System (HITS) to record head impact biomechanics, we sought to correlate pre- and post-concussive impact characteristics with declines in cognitive performance and increases in concussion-related symptoms. Over four seasons, 19 high school football athletes wearing instrumented helmets sustained 20 diagnosed concussions. Each athlete completed a baseline computer-based symptom and cognitive assessment during the pre-season and a post-injury assessment within 24 h of injury. Correlational analyses identified no significant relationships between symptoms and cognitive performance change scores and impact biomechanics (i.e., time from session start until injury, time from the previous impact, peak linear acceleration, peak rotational acceleration, and HIT severity profile [HITsp]). Nor were there any significant relationships between change scores and the number of impacts, cumulative linear acceleration, cumulative rotational acceleration, or cumulative HITsp values associated with all impacts prior to or following the injury. This investigation is the first to examine the relationship between concussion impact characteristics, including cumulative impact profiles, and post-morbid outcomes in high school athletes. There appears to be no association between head impact biomechanics and post-concussive outcomes. As such, the use of biomechanical variables to predict injury severity does not appear feasible at this time. PMID:21644811

  16. Post-concussion cognitive declines and symptomatology are not related to concussion biomechanics in high school football players.

    PubMed

    Broglio, Steven P; Eckner, James T; Surma, Tyler; Kutcher, Jeffrey S

    2011-10-01

    Concussion is a major public health concern with nearly 4 million injuries occurring each year in the United States. In the acute post-injury stage, concussed individuals demonstrate cognitive function and motor control declines as well as reporting increased symptoms. Researchers have hypothesized that the severity of these impairments is related to impact magnitude. Using the Head Impact Telemetry System (HITS) to record head impact biomechanics, we sought to correlate pre- and post-concussive impact characteristics with declines in cognitive performance and increases in concussion-related symptoms. Over four seasons, 19 high school football athletes wearing instrumented helmets sustained 20 diagnosed concussions. Each athlete completed a baseline computer-based symptom and cognitive assessment during the pre-season and a post-injury assessment within 24 h of injury. Correlational analyses identified no significant relationships between symptoms and cognitive performance change scores and impact biomechanics (i.e., time from session start until injury, time from the previous impact, peak linear acceleration, peak rotational acceleration, and HIT severity profile [HITsp]). Nor were there any significant relationships between change scores and the number of impacts, cumulative linear acceleration, cumulative rotational acceleration, or cumulative HITsp values associated with all impacts prior to or following the injury. This investigation is the first to examine the relationship between concussion impact characteristics, including cumulative impact profiles, and post-morbid outcomes in high school athletes. There appears to be no association between head impact biomechanics and post-concussive outcomes. As such, the use of biomechanical variables to predict injury severity does not appear feasible at this time.

  17. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease

    PubMed Central

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID:27190672

  18. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease.

    PubMed

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice.

  19. Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

    PubMed Central

    Lawrence, Andrew J.; Brookes, Rebecca L.; Zeestraten, Eva A.; Barrick, Thomas R.; Morris, Robin G.; Markus, Hugh S.

    2015-01-01

    Objectives Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline. Methods 121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points. Results Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up. Conclusions The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease. PMID:26273828

  20. Obstructive Sleep Apnea and 15-Year Cognitive Decline: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Lutsey, Pamela L.; Bengtson, Lindsay G.S.; Punjabi, Naresh M.; Shahar, Eyal; Mosley, Thomas H.; Gottesman, Rebecca F.; Wruck, Lisa M.; MacLehose, Richard F.; Alonso, Alvaro

    2016-01-01

    Study Objectives: Prospective data evaluating abnormal sleep quality and quantity with cognitive decline are limited because most studies used subjective data and/or had short follow-up. We hypothesized that, over 15 y of follow-up, participants with objectively measured obstructive sleep apnea (OSA) and other indices of poor sleep quantity and quality would experience greater decline in cognitive functioning than participants with normal sleep patterns. Methods: ARIC participants (n = 966; mean age 61 y, 55% women) with in-home polysomnography (1996–1998) and repeated cognitive testing were followed for 15 y. Three cognitive tests (Delayed Word Recall, Word Fluency, and Digit Symbol Substitution) were administered at two time points (1996–1998 and 2011–2013). Ten additional cognitive tests were administered at the 2011–2013 neurocognitive examination. OSA was modeled using established clinical OSA severity categories. Multivariable linear regression was used to explore associations of OSA and other sleep indices with change in cognitive tests between the two assessments. Results: A median of 14.9 y (max: 17.3) passed between the two cognitive assessments. OSA category and additional indices of sleep (other measures of hypoxemia and disordered breathing, sleep fragmentation, sleep duration) were not associated with change in any cognitive test. Analyses of OSA severity categories and 10 cognitive tests administered only in 2011–2013 also showed little evidence of an association. Conclusions: Overall, abnormal sleep quality and quantity at midlife was not related to cognitive decline and later-life cognition. The effect of adverse sleep quality and quantity on cognitive decline among the elderly remains to be determined. Citation: Lutsey PL, Bengtson LG, Punjabi NM, Shahar E, Mosley TH, Gottesman RF, Wruck LM, MacLehose RF, Alonso A. Obstructive sleep apnea and 15-year cognitive decline: the Atherosclerosis Risk in Communities (ARIC) study. SLEEP 2016

  1. Relationship between changes of body mass index (BMI) and cognitive decline in Parkinson's disease (PD).

    PubMed

    Kim, Hyun Jung; Oh, Eung Seok; Lee, Ji Hee; Moon, Jung Soo; Oh, Ji Eun; Shin, Jong Wook; Lee, Kyung Jae; Baek, In Chul; Jeong, Seong-Hae; Song, Hee-Jung; Sohn, Eun Hee; Lee, Ae Young

    2012-01-01

    Decreased BMI has been reported that it may be associated with cognitive decline in the elderly. Weight loss is common in patients with PD. However, studies comparing cognitive changes according to BMI changes in PD have not been done yet. We performed this study to know a relationship between BMI changes and the rate of cognitive decline in PD. PD patients were recruited retrospectively. The patients (n=104) were divided into two groups according to BMI changes during initial 6 months of follow-up: decreased (n=52) vs. stable BMI groups (n=52). Cognitive functions were repeated until 36 months of follow-up using the Korean version of the Mini-Mental State Examination (K-MMSE) and the modified Mini-Mental State (3MS) test. We calculated the rate of cognitive decline (K-MMSE and 3MS score changes/month) and compared it between the two groups. The decreased BMI group showed lower level of cognitive function than that of stable BMI group, especially at the 36th month of follow-up (p<0.05). In addition, the rate of cognitive decline was also significantly faster in the decreased BMI group, particularly at the 36th month of follow-up (p<0.05). This study suggests that decreased BMI during initial 6 months of follow-up in PD might be a useful indicator for future risk of dementia and let clinicians predict faster rate of cognitive decline in patients with PD.

  2. Adverse Oral Health and Cognitive Decline: The Health, Aging and Body Composition Study

    PubMed Central

    Stewart, Robert; Weyant, Robert J.; Garcia, Melissa E.; Harris, Tamara; Launer, Lenore J.; Satterfield, Suzanne; Simonsick, Eleanor M.; Yaffe, Kristine; Newman, Anne B.

    2012-01-01

    Background/Objectives Periodontal disease has been associated with poorer cross-sectional cognitive function and is correlated with adverse vascular outcomes, but has received little prospective investigation in relation to cognitive decline. Design Analysis of a prospective cohort study. Setting The Health, Aging and Body Composition (Health ABC) Study Participants and measurements We examined the prospective association between a range of oral health parameters and cognitive function using data on 1053 participants who were administered the Modified Mini-Mental State Examination (3MS) at year 1 (baseline) and year 3, and had participated in a comprehensive periodontal examination at year 2. We investigated 3MS decline from year 3 to 5 in 947 (89.9%) participants. Covariates included age, sex, education, race, cardiovascular disease/risk and depressive symptoms. Results Most indicators of adverse oral health at year 2 were associated with cognitive impairment based on averaged 3MS scores <80 for years 1 and 3, but these associations were substantially confounded by education and race. Higher gingival index, a measure of gingival inflammation, at year 2 remained independently associated with this definition of cognitive impairment and, in fully adjusted analyses, was also an independent predictor of a 5+ point cognitive decline from years 3 to 5. Conclusion Periodontitis may be a risk factor for cognitive decline. Gingivitis is reversible and periodontitis to some degree is preventable and controllable when manifest. Therefore, further research is needed to clarify potential underlying mechanisms and oral health interventions that potentially might ameliorate cognitive decline. PMID:23405916

  3. Cerebral amyloidosis associated with cognitive decline in autosomal dominant Alzheimer disease.

    PubMed

    Wang, Fen; Gordon, Brian A; Ryman, Davis C; Ma, Shengmei; Xiong, Chengjie; Hassenstab, Jason; Goate, Alison; Fagan, Anne M; Cairns, Nigel J; Marcus, Daniel S; McDade, Eric; Ringman, John M; Graff-Radford, Neill R; Ghetti, Bernardino; Farlow, Martin R; Sperling, Reisa; Salloway, Steve; Schofield, Peter R; Masters, Colin L; Martins, Ralph N; Rossor, Martin N; Jucker, Mathias; Danek, Adrian; Förster, Stefan; Lane, Christopher A S; Morris, John C; Benzinger, Tammie L S; Bateman, Randall J

    2015-09-01

    To investigate the associations of cerebral amyloidosis with concurrent cognitive performance and with longitudinal cognitive decline in asymptomatic and symptomatic stages of autosomal dominant Alzheimer disease (ADAD). Two hundred sixty-three participants enrolled in the Dominantly Inherited Alzheimer Network observational study underwent neuropsychological evaluation as well as PET scans with Pittsburgh compound B. One hundred twenty-one participants completed at least 1 follow-up neuropsychological evaluation. Four composite cognitive measures representing global cognition, episodic memory, language, and working memory were generated using z scores from a battery of 13 standard neuropsychological tests. General linear mixed-effects models were used to investigate the relationship between baseline cerebral amyloidosis and baseline cognitive performance and whether baseline cerebral amyloidosis predicts cognitive change over time (mean follow-up 2.32 years ± 0.92, range 0.89-4.19) after controlling for estimated years from expected symptom onset, APOE ε4 allelic status, and education. In asymptomatic mutation carriers, amyloid burden was not associated with baseline cognitive functioning but was significantly predictive of longitudinal decline in episodic memory. In symptomatic mutation carriers, cerebral amyloidosis was correlated with worse baseline performance in multiple cognitive composites and predicted greater decline over time in global cognition, working memory, and Mini-Mental State Examination. Cerebral amyloidosis predicts longitudinal episodic memory decline in presymptomatic ADAD and multidomain cognitive decline in symptomatic ADAD. These findings imply that amyloidosis in the brain is an indicator of early cognitive decline and provides a useful outcome measure for early assessment and prevention treatment trials. © 2015 American Academy of Neurology.

  4. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease

    PubMed Central

    Alosco, Michael L.; Forman, Daniel E.

    2015-01-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns. PMID:25750853

  5. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease.

    PubMed

    Hayes, Scott M; Alosco, Michael L; Forman, Daniel E

    2014-12-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns.

  6. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    PubMed

    Cho, Kyung-Ok; Lybrand, Zane R; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G; Birnbaum, Shari G; Scharfman, Helen E; Eisch, Amelia J; Hsieh, Jenny

    2015-03-26

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

  7. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

    PubMed Central

    Cho, Kyung-Ok; Lybrand, Zane R.; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G.; Birnbaum, Shari G.; Scharfman, Helen E.; Eisch, Amelia J.; Hsieh, Jenny

    2015-01-01

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult. PMID:25808087

  8. Computerized and virtual reality cognitive training for individuals at high risk of cognitive decline: systematic review of the literature.

    PubMed

    Coyle, Hannah; Traynor, Victoria; Solowij, Nadia

    2015-04-01

    The aim of this study was to assess the efficacy of cognitive training, specifically computerized cognitive training (CCT) and virtual reality cognitive training (VRCT), programs for individuals living with mild cognitive impairment (MCI) or dementia and therefore at high risk of cognitive decline. After searching a range of academic databases (CINHAL, PSYCinfo, and Web of Science), the studies evaluated (N = 16) were categorized as CCT (N = 10), VRCT (N = 3), and multimodal interventions (N = 3). Effect sizes were calculated, but a meta-analysis was not possible because of the large variability of study design and outcome measures adopted. The cognitive domains of attention, executive function, and memory (visual and verbal) showed the most consistent improvements. The positive effects on psychological outcomes (N = 6) were significant reductions on depressive symptoms (N = 3) and anxiety (N = 2) and improved perceived use of memory strategy (N = 1). Assessments of activities of daily living demonstrated no significant improvements (N = 8). Follow-up studies (N = 5) demonstrated long-term improvements in cognitive and psychological outcomes (N = 3), and the intervention groups showed a plateau effect of cognitive functioning compared with the cognitive decline experienced by control groups (N = 2). CCT and VRCT were moderately effective in long-term improvement of cognition for those at high risk of cognitive decline. Total intervention time did not mediate efficacy. Future research needs to improve study design by including larger samples, longitudinal designs, and a greater range of outcome measures, including functional and quality of life measures, to assess the wider effect of cognitive training on individuals at high risk of cognitive decline. Copyright © 2015. Published by Elsevier Inc.

  9. Effects of NSAID treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: Findings from the randomized controlled ADAPT trial

    PubMed Central

    Leoutsakos, Jeannie-Marie S.; Muthen, Bengt O.; Breitner, John C.S.; Lyketsos, Constantine G.

    2011-01-01

    Objective We examined effects of non-steroidal anti-inflammatory drugs (NSAID) on cognitive decline as a function of phase of pre-clinical Alzheimer’s disease (AD). Methods Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer’s disease. We fit growth mixture models of Modified Mini-Mental State Examination (3MS) trajectories with data from 2,388 participants in the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT), and included class-specific effects of naproxen and celecoxib. Results We identified 3 classes: “no-decline”, “slow-decline”, and “fast-decline”, and examined effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (−2 log likelihood difference: 369.23; p<0.001), but resulted in reversal of effects over time. Over four years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, while those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), while those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Conclusions Our results appeared statistically robust, but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then to attenuate change in fast decliners. PMID:21560159

  10. 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/

  11. Lower Circulating Progenitor cells is related to greater cognitive decline in healthy adults

    PubMed Central

    Hajjar, Ihab; Goldstein, Felicia C.; Waller, Edmund K.; Moss, Lauren D.; Quyyumi, Arshed

    2015-01-01

    Objective Cognitive and cardiovascular disorders share many risk factors. Higher bone-marrow derived progenitor cells (PC) in blood are associated with lower rates of cardiovascular events but the association of PC with cognitive function is unclear. The objective of this study was to assess the association between PC and cognition in a sample of healthy adults enrolled in a cohort study Methods A random sample of employees at Emory University and Georgia Institute of Technology were followed for 4 years and underwent yearly vascular and cognitive assessment (N=430, mean age=49.2 years, 70% women, and 27% African American). Cognition was assessed using computerized versions of 15 cognitive tests and principal component analysis was used for deriving cognitive scores: executive function, memory and working memory. PC were defined as mononuclear cells with specific surface markers (7 phenotypes). Decreased cognition in a domain was defined as performing below the lowest quartile for the corresponding domain at baseline. Generalized estimating equations were used to investigate associations between PC and cognition. Results Higher PC levels at baseline were associated with lower risk of cognitive decline in the executive and working memory domains during the follow-up period (p<0.002 for all PC phenotypes). Further, the degree of decline in PC over the follow-up period was correlated with a corresponding decline in performances in all 3 cognitive domains over the same period (All p<0.002). Interpretation Lower PC and greater yearly declines in PC are associated with greater cognitive decline. These findings suggest role for PC in neurocognitive aging. PMID:26897269

  12. Body mass and cognitive decline are indirectly associated via inflammation among aging adults.

    PubMed

    Bourassa, Kyle; Sbarra, David A

    2017-02-01

    Inflammatory models of neurodegeneration suggest that higher circulating levels of inflammation can lead to cognitive decline. Despite established independent associations between greater body mass, increased inflammation, and cognitive decline, no prior research has explored whether markers of systemic inflammation might mediate the association between body mass and changes in cognitive functioning. To test such a model, we used two longitudinal subsamples (ns=9066; 12,561) of aging adults from the English Longitudinal Study of Ageing (ELSA) study, which included two cognitive measures components of memory and executive functioning, as well as measurements of body mass and systemic inflammation, assessed via C-reactive protein (CRP). Greater body mass was indirectly associated with declines in memory and executive functioning over 6years via relatively higher levels of CRP. Our results suggest that systemic inflammation is one biologically plausible mechanism through which differences in body mass might influence changes in cognitive functioning among aging adults.

  13. Rate of Cognitive Decline Before and After the Onset of Functional Limitations in Older Persons

    PubMed Central

    Rajan, Kumar B.; Hebert, Liesi E.; Scherr, Paul A.; Mendes de Leon, Carlos F.; Evans, Denis A.

    2015-01-01

    Background: Loss in physical function is indicative of deterioration in physiological health that may also be associated with deterioration in neurological health. The objective of this study was to examine whether the onset of functional limitations and their severity is associated with increases in cognitive decline among older adults. Methods: The study sample consists of 3825 (65% African Americans and 53% females) participants over the age of 65 with no functional limitations. Cognitive function was assessed using a standardized global cognitive score, and functional limitations using a summary measure of 8 Rosow-Breslau and Nagi limitations (ROS-B/Nagi). Cognitive decline before and after the onset of limitations were analyzed using a linear piecewise change point model. Results: During follow-up, 2682 (70%) participants reported limitations in ROS-B/Nagi measure. The rate of cognitive decline was 0.053-units per year before any limitations, and increased to 0.069-units per year after one or more limitations in ROS-B/Nagi measure. This was about 30% (95% Confidence Interval [CI]: 18 – 42%) increase in the rate of cognitive decline comparing before and after the onset of limitations in ROS-B/Nagi measure. Also, higher number of limitations in ROS-B/Nagi measure at the time of onset was associated with faster cognitive decline. Conclusions: The rate of cognitive decline was significantly higher following functional limitations. This study suggests that self-reported measures of functional limitations may serve as an important marker of cognitive decline. PMID:25934994

  14. Rate of Cognitive Decline Before and After the Onset of Functional Limitations in Older Persons.

    PubMed

    Rajan, Kumar B; Hebert, Liesi E; Scherr, Paul A; Mendes de Leon, Carlos F; Evans, Denis A

    2015-10-01

    Loss in physical function is indicative of deterioration in physiological health that may also be associated with deterioration in neurological health. The objective of this study was to examine whether the onset of functional limitations and their severity is associated with increases in cognitive decline among older adults. The study sample consists of 3825 (65% African Americans and 53% females) participants over the age of 65 with no functional limitations. Cognitive function was assessed using a standardized global cognitive score, and functional limitations using a summary measure of 8 Rosow-Breslau and Nagi limitations (ROS-B/Nagi). Cognitive decline before and after the onset of limitations were analyzed using a linear piecewise change point model. During follow-up, 2682 (70%) participants reported limitations in ROS-B/Nagi measure. The rate of cognitive decline was 0.053-units per year before any limitations, and increased to 0.069-units per year after one or more limitations in ROS-B/Nagi measure. This was about 30% (95% Confidence Interval [CI]: 18 - 42%) increase in the rate of cognitive decline comparing before and after the onset of limitations in ROS-B/Nagi measure. Also, higher number of limitations in ROS-B/Nagi measure at the time of onset was associated with faster cognitive decline. The rate of cognitive decline was significantly higher following functional limitations. This study suggests that self-reported measures of functional limitations may serve as an important marker of cognitive decline. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Cognitive Decline, Body Mass Index, and Waist Circumference in Community-Dwelling Elderly Participants.

    PubMed

    Rodríguez-Fernández, Jorge Mario; Danies, Emily; Martínez-Ortega, José; Chen, William C

    2017-03-01

    The aim of this study was to explore the association of body mass index (BMI), waist circumference (WC), and BMI and WC changes over time with cognitive decline in a nationally representative sample. A total of 5239 participants (≥65 years) were followed for 3 years as part of the National Health and Aging Trends Study. Cox proportional hazard regression was applied to model the risk of cognitive decline. BMI, after adjusting for WC and main confounders, was associated with reduced risk of cognitive decline (hazard ratio [HR] 0.97 for each unit BMI increase, 0.95-0.99). After stratifying by gender and age, this effect remained significant among females and young elders ≤80 years. A BMI decrease and WC increase >10% over the study period were associated with increased risk of cognitive decline (HR 1.98, 1.16-3.38; HR 1.30, 1.04-1.62, respectively). In the elderly individuals, lean mass, as measured by BMI adjusted for WC, was associated with reduced risk of cognitive decline. Loss of lean mass and gain of fat mass, as measured by WC adjusted for BMI, were associated with elevated risk of cognitive decline.

  16. Education and Age-Related Cognitive Decline: The Contribution of Mental Workload.

    ERIC Educational Resources Information Center

    Bosma, H.; van Boxtel, M. P. J.; Ponds, R. W. H. M.; Houx, P. J. H.; Jolles, J.

    2003-01-01

    Longitudinal data from a Dutch study of 708 older adults showed that persons with low educational attainment experienced more decline in information processing speed, memory, and cognitive function. About 42% of the variance was explained by low stimulus or challenge in work. Decline was independent of crystallized intelligence. (Contains 24…

  17. Food Insecurity Is Associated with Subsequent Cognitive Decline in the Boston Puerto Rican Health Study.

    PubMed

    Wong, Janice C; Scott, Tammy; Wilde, Parke; Li, Yin-Ge; Tucker, Katherine L; Gao, Xiang

    2016-09-01

    Living with hunger and fear of not having enough food is a growing worldwide concern. In our previous cross-sectional study, we found that food insecurity was associated with poor cognitive function, but the direction of this relation remains unclear. We investigated whether food insecurity is associated with subsequent cognitive decline. This was a longitudinal study of 597 participants aged 40-75 y from the Boston Puerto Rican Health Study cohort, with a Mini-Mental State Examination score of ≥24 at baseline. Food security was assessed at baseline with the US Household Food Security Scale. Participants completed cognitive batteries, which included 7 cognitive tests, twice-at baseline and again at a 2-y follow-up. The primary outcome was the change in global cognitive function over 2 y. Multiple linear regression was used to obtain adjusted mean differences and 95% CIs in cognitive decline across baseline food security status. Food insecurity at baseline was associated with a 2-y decline in global cognitive function (P-trend = 0.03) after adjusting for relevant potential confounders, including age, sex, baseline cognitive score, body mass index, education, poverty, acculturation score, depression score, smoking status, use of alcohol, physical activity score, presence of diabetes and hypertension, apolipoprotein E status, plasma homocysteine, healthy eating index, and time between baseline and follow-up measures. Compared with the food-secure group, the decline in the very low food security group was greater [mean difference: -0.26 (95% CI: -0.41, -0.10)]. Baseline food insecurity was significantly associated with a faster decline in executive function (P-trend = 0.02) but not memory function (P-trend = 0.66). Food insecurity was associated with faster cognitive decline in this cohort of Puerto Rican adults. Our study emphasizes the importance of developing interventions for food insecurity that take into account the impact of food insecurity on cognition.

  18. Effect of plasma lipids and APOE genotype on cognitive decline.

    PubMed

    Yasuno, Fumihiko; Asada, Takashi

    2013-03-01

    A central tenet of brain aging is that "what is good for the heart is good for the brain." We examined the combined effect of plasma lipids and APOE genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein, triglyceride, total cholesterol, and apolipoprotein E (apoE) were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids and cognitive function in APOE4 carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma apoE levels in both E4- and E4+, and HDL level in E4-. Our findings suggest that an interaction between apoE and HDL is facilitated by APOE4, and is possibly linked with an enhancement of neuroplasticity and with resultant protective effects on cognitive function in later life. Preservation of higher plasma apoE and HDL from early life is proposed as a possible strategy for maintaining cognitive function in later life, especially for APOE4-positive individuals.

  19. Genetic architecture of age-related cognitive decline in African Americans.

    PubMed

    Raj, Towfique; Chibnik, Lori B; McCabe, Cristin; Wong, Andus; Replogle, Joseph M; Yu, Lei; Gao, Sujuan; Unverzagt, Frederick W; Stranger, Barbara; Murrell, Jill; Barnes, Lisa; Hendrie, Hugh C; Foroud, Tatiana; Krichevsky, Anna; Bennett, David A; Hall, Kathleen S; Evans, Denis A; De Jager, Philip L

    2017-02-01

    To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.

  20. Genetic architecture of age-related cognitive decline in African Americans

    PubMed Central

    Raj, Towfique; Chibnik, Lori B.; McCabe, Cristin; Wong, Andus; Replogle, Joseph M.; Yu, Lei; Gao, Sujuan; Unverzagt, Frederick W.; Stranger, Barbara; Murrell, Jill; Barnes, Lisa; Hendrie, Hugh C.; Foroud, Tatiana; Krichevsky, Anna; Bennett, David A.; Hall, Kathleen S.; Evans, Denis A.

    2016-01-01

    Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD. PMID:28078323

  1. Association of Delirium With Cognitive Decline in Late Life: A Neuropathologic Study of 3 Population-Based Cohort Studies.

    PubMed

    Davis, Daniel H J; Muniz-Terrera, Graciela; Keage, Hannah A D; Stephan, Blossom C M; Fleming, Jane; Ince, Paul G; Matthews, Fiona E; Cunningham, Colm; Ely, E Wesley; MacLullich, Alasdair M J; Brayne, Carol

    2017-03-01

    Delirium is associated with accelerated cognitive decline. The pathologic substrates of this association are not yet known, that is, whether they are the same as those associated with dementia, are independent, or are interrelated. To examine whether the accelerated cognitive decline observed after delirium is independent of the pathologic processes of classic dementia. Harmonized data from 987 individual brain donors from 3 observational cohort studies with population-based sampling (Vantaa 85+, Cambridge City Over-75s Cohort, Cognitive Function and Ageing Study) performed from January 1, 1985, through December 31, 2011, with a median follow-up of 5.2 years until death, were used in this study. Neuropathologic assessments were performed with investigators masked to clinical data. Data analysis was performed from January 1, 2012, through December 31, 2013. Clinical characteristics of brain donors were not different from the rest of the cohort. Outcome ascertainment was complete given that the participants were brain donors. Delirium (never vs ever) and pathologic burden of neurofibrillary tangles, amyloid plaques, vascular lesions, and Lewy bodies. Effects modeled using random-effects linear regression and interactions between delirium and pathologic burden were assessed. Change in Mini-Mental State Examination (MMSE) scores during the 6 years before death. There were 987 participants (290 from Vantaa 85+, 241 from the Cambridge City Over-75s Cohort, and 456 from the Cognitive Function and Ageing Study) with neuropathologic data; mean (SD) age at death was 90 (6.4) years, including 682 women (69%). The mean MMSE score 6 years before death was 24.7 points. The 279 individuals with delirium (75% women) had worse initial scores (-2.8 points; 95% CI, -4.5 to -1.0; P < .001). Cognitive decline attributable to delirium was -0.37 MMSE points per year (95% CI, -0.60 to -0.13; P < .001). Decline attributable to the pathologic processes of dementia was -0.39 MMSE

  2. Cerebrovascular resistance: effects on cognitive decline, cortical atrophy, and progression to dementia.

    PubMed

    Yew, Belinda; Nation, Daniel A

    2017-07-01

    resistance index was significantly elevated in amyloid-positive versus amyloid-negative cases, with additional elevation in patients with Alzheimer's disease. Furthermore, cerebrovascular resistance index group differences were of greater statistical effect size and encompassed a greater number of brain regions than those for cerebral blood flow alone. Cognitive decline over 2-year follow-up was accelerated by elevated baseline cerebrovascular resistance index, particularly for amyloid-positive individuals. Increased baseline cerebrovascular resistance index also predicted greater progression to dementia, beyond that attributable to amyloid-positivity. Finally, increased cerebrovascular resistance index predicted greater regional atrophy among non-demented older adults who were amyloid-negative. Findings suggest that increased cerebrovascular resistance may represent a previously unrecognized contributor to Alzheimer's disease that is independent of neuronal hypometabolism, predates changes in brain perfusion, exacerbates and works synergistically with amyloidosis to produce cognitive decline, and drives amyloid-independent brain atrophy during the earliest stage of disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level.

  4. An Evaluation of the Evidence that Methamphetamine Abuse Causes Cognitive Decline in Humans

    PubMed Central

    Dean, Andy C; Groman, Stephanie M; Morales, Angelica M; London, Edythe D

    2013-01-01

    Methamphetamine (MA) is one of the most commonly abused illicit substances worldwide. Among other problems, abuse of the drug has been associated with reduced cognitive function across several domains. However, much of the literature has not attempted to differentiate cognitive difficulties caused by MA abuse from preexisting cognitive difficulties that are likely caused by other factors. Here, we address this question, evaluating evidence for a priori hypotheses pertaining to six lines of research: (a) animal studies; (b) cross-sectional human studies; (c) a twin study; (d) studies of changes in cognition with abstinence from MA; (e) studies of changes in brain structure and function with abstinence from MA; and (f) studies of the relationship between the severity of MA abuse and the extent of cognitive deficits observed. Overall the findings were mixed, with some support for a causal relationship between MA abuse and cognitive decline, and other findings suggesting that there is no relationship. The preponderance of the data, however, does support the possibility that MA abuse causes cognitive decline, of unknown duration, in at least some users of the drug. When averaged across individuals, this decline is likely to be mild in early-to-middle adulthood. However, moderator variables are likely to contribute to the presence and/or severity of cognitive decline exhibited by a given individual. PMID:22948978

  5. The role of B-vitamins in preventing and treating cognitive impairment and decline

    USDA-ARS?s Scientific Manuscript database

    Many epidemiologic studies have considered the question of whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease (CVD), which was extended to Alzheimer’s disease...

  6. 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...

  7. The Utility of the Cognitive Function Instrument (CFI) to Detect Cognitive Decline in Non-Demented Older Adults.

    PubMed

    Li, Clara; Neugroschl, Judith; Luo, Xiaodong; Zhu, Carolyn; Aisen, Paul; Ferris, Steven; Sano, Mary

    2017-01-01

    Subjective cognitive complaint is a sensitive marker of decline. This study aimed to (1) examine reliability of subjective cognitive complaint using the Cognitive Function Instrument (CFI), and (2) assess the utility of the CFI to detect cognitive decline in non-demented elders. Data from a four-year longitudinal study at multiple Alzheimer's Disease Cooperative Study (ADCS) sites were extracted (n = 644). Of these, 497 had Clinical Dementia Rating (CDR) global scores of 0 and 147 had a CDR of 0.5. Mean age and education were 79.5±3.6 and 15.0±3.1 years, respectively. All participants and their study partners completed the subject and study partner CFI yearly. Modified Mini-Mental State Exam (mMMSE) and Free and Cued Selective Reminding Test (FCSRT) were administered. Scores below the predetermined cut-off scores on either measure at annual visit were triggers for a full diagnostic evaluation. Cognitive decline was defined by the absence/presence of the trigger. Three-month test retest reliability showed that inter-class coefficients for subject and study partner CFI were 0.76 and 0.78, respectively. Generalized estimating equation method revealed that both subject and study partner CFI change scores and scores from previous year were sensitive to cognitive decline in the CDR 0 group (p < 0.05). In the CDR 0.5 group, only the study partner CFI change score predicted cognitive decline (p < 0.05). Cognitive decline was predicted differentially by CDR level with subject CFI scores providing the best prediction for those with CDR 0 while study partner CFI predicted best for those at CDR 0.5.

  8. Clinical workout for the early detection of cognitive decline and dementia.

    PubMed

    Tsolaki, M

    2014-11-01

    Aging is the major risk factor for the development of human neurodegenerative maladies such as Alzheimer's, Huntington's and Parkinson's diseases (PDs) and prion disorders, all of which stem from toxic protein aggregation. All of these diseases are correlated with cognitive decline. Cognitive Decline is a dynamic state from normal cognition of aging to dementia. According to the original criteria for Alzheimer's Disease (AD) (1984), a clinical diagnosis was possible only when someone was already demented. The prevalence rates of Cognitive Decline (mild cognitive impairment plus dementia) are very high now and will be higher in future because of the increasing survival time of people. Many neurological and psychiatric diseases are correlated with cognitive decline. Diagnosis of cognitive decline is mostly clinical (clinical criteria), but there are multiple biomarkers that could help us mostly in research programs such as short or long, paper and pencil or computerized neuropsychological batteries for cognition, activities of daily living and behavior, electroencephalograph, event-related potentials, and imaging-structural magnetic resonance imaging (MRI) and functional (fMRI, Pittsburgh bound positron emission tomography, FDG-PET, single photon emission computerized tomography and imaging of tau pathology)-cerebrospinal fluid proteins (Abeta, tau and phospho-tau in AD and α-synuclein (αSyn) for PD). Blood biomarkers need more studies to confirm their usefulness. Genetic markers are also studied but until now are not used in clinical praxis. Finally, in everyday clinical praxis and in research workout for early detection of cognitive decline, the combination of biomarkers is useful.

  9. Biomarkers in subtypes of mild cognitive impairment and subjective cognitive decline.

    PubMed

    Eliassen, Carl F; Reinvang, Ivar; Selnes, Per; Grambaite, Ramune; Fladby, Tormod; Hessen, Erik

    2017-09-01

    Preclinical Alzheimers disease (AD) patients may or may not show cognitive impairment on testing. AD biomarkers are central to the identification of those at low, intermediate, or high risk of later dementia due to AD. We investigated biomarker distribution in those identified as subjective cognitive decline (SCD), amnestic (aMCI), and nonamnestic (naMCI) mild cognitive impairment (MCI) subtypes. In addition, the clinical groups were compared with controls on downstream neuroimaging markers. Cerebrospinal fluid (CSF) amyloid-β42 (A β42) and total tau (t-tau), phosphorylated tau (p-tau), fluorodeoxyglucose (FDG), positron-emission tomography (PET), and MRI neuroimaging measures were collected from 116 memory clinic patients. They were characterized as SCD, aMCI, and naMCI according to comprehensive neuropsychological criteria. ANOVAs were used to assess differences when biomarkers were treated as continuous variables and chi square analyses were used to assess group differences in distribution of biomarkers. We did not find any between group differences in Aβ42, nor in p-tau, but we observed elevated t-tau in aMCI and SCD relative to the naMCI group. Significantly lower cortical glucose metabolism (as measured by FDG PET) was found in aMCI relative to SCD and controls, and there was a trend for lower metabolism in naMCI. Significant thinner entorhinal cortex (ERC) was found in aMCI and SCD. As expected biomarkers were significantly more frequently pathological in aMCI than in naMCI and SCD, whereas the naMCI and SCD groups displayed similar pathological biomarker burden. aMCI cases show the most pathologic biomarker burden. Interestingly naMCI and SCD subjects show similar levels of pathological biomarkers albeit the former displayed neuropsychological deficits. That the latter group may represent a risk group is supported by our observation of both elevated CSF tau and thinner ERC relative to controls.

  10. MRI Markers Predict Cognitive Decline Assessed by Telephone Interview: The Northern Manhattan Study.

    PubMed

    Wright, Clinton B; Dong, Chuanhui; Caunca, Michelle R; DeRosa, Janet; Kuen Cheng, Ying; Rundek, Tatjana; Elkind, Mitchell S V; DeCarli, Charles; Sacco, Ralph L

    2017-01-01

    Brain magnetic resonance imaging (MRI) allows researchers to observe structural pathology that may predict cognitive decline. Some populations are less accessible through traditional in-person visits, and may be under-represented in the literature. We examined white matter hyperintensity volume (WMHV) and cerebral parenchymal fraction (CPF) as predictors of cognitive decline measured by a modified Telephone Interview for Cognitive Status (TICS-m) in the Northern Manhattan Stroke Study, a racially and ethnically diverse cohort study. Participants were stroke-free, above 50 years old, and had no contraindications to MRI. A total of 1143 participants had MRI and TICS-m data available [mean age 70 (SD=9), 61% women, 66% Hispanic, 17% Black, 15% white]. Those in the third and fourth quartiles of WMHV had significantly greater decline in TICS-m over time as compared with those in the first quartile (Q3: -0.17 points/year, Q4: -0.30 points/year). Those in the bottom 2 quartiles of CPF had significantly greater decline in TICS-m than those in the top quartile (Q1: -0.3 points/year, Q2: -0.2 points/year). Apolipoprotein E (APOE) e4 allele carriers had greater cognitive decline per unit of CPF. Those with greater CPF preserve TICS-m performance better despite greater WMHV. Telephone cognitive assessments can detect decline due to white matter lesions and smaller brain volumes.

  11. A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimer’s disease

    PubMed Central

    2014-01-01

    Introduction The aim of this review was to investigate whether there is a faster cognitive decline in dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD) over time. Methods PsycINFO and Medline were searched from 1946 to February 2013. A quality rating from 1 to 15 (best) was applied to the included studies. A quantitative meta-analysis was done on studies with mini mental state examination (MMSE) as the outcome measure. Results A total of 18 studies were included. Of these, six (36%) reported significant differences in the rate of cognitive decline. Three studies reported a faster cognitive decline on MMSE in patients with mixed DLB and AD compared to pure forms, whereas two studies reported a faster decline on delayed recall and recognition in AD and one in DLB on verbal fluency. Mean quality scores for studies that did or did not differ were not significantly different. Six studies reported MMSE scores and were included in the meta-analysis, which showed no significant difference in annual decline on MMSE between DLB (mean 3.4) and AD (mean 3.3). Conclusions Our findings do not support the hypothesis of a faster rate of cognitive decline in DLB compared to AD. Future studies should apply recent diagnostic criteria, as well as extensive diagnostic evaluation and ideally autopsy diagnosis. Studies with large enough samples, detailed cognitive tests, at least two years follow up and multivariate statistical analysis are also needed. PMID:25478024

  12. ω-3 fatty acids and cognitive decline: modulation by ApoEε4 allele and depression.

    PubMed

    Samieri, Cécilia; Féart, Catherine; Proust-Lima, Cécile; Peuchant, Evelyne; Dartigues, Jean-François; Amieva, Hélène; Barberger-Gateau, Pascale

    2011-12-01

    Long-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may slow cognitive decline. The ε4 allele of the ApolipoproteinE (ApoE), the main genetic risk factor for Alzheimer's disease, and depressive symptoms, which are frequently associated with cognitive impairment in older persons, may modify this relationship. We estimated the associations between EPA and DHA plasma levels and subsequent cognitive decline over 7 years, taking into account ApoE-ε4 status and depressive symptoms, in a prospective population-based cohort. Participants (≥ 65 years, n = 1,228 nondemented at baseline) were evaluated at least once over three follow-up visits using four cognitive tests. Plasma EPA was associated with slower decline on Benton Visual Retention Test (BVRT) performances in ApoE-ε4 carriers, or in subjects with high depressive symptoms at baseline. Plasma DHA was associated with slower decline on BVRT performances in ApoE-ε4 carriers only. EPA and DHA may contribute to delaying decline in visual working memory in ApoE-ε4 carriers. In older depressed subjects, EPA, but not DHA, may slow cognitive decline.

  13. 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

  14. 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.

  15. Association between tooth loss and cognitive decline: A 13-year longitudinal study of Chinese older adults

    PubMed Central

    Li, Juan; Xu, Hanzhang; Pan, Wei; Wu, Bei

    2017-01-01

    Objectives To examine the association between the number of teeth remaining and cognitive decline among Chinese older adults over a 13-year period. Design A large national longitudinal survey of Chinese older adults Setting The Chinese Longitudinal Healthy Longevity Survey (CLHLS) (1998–2011). Participants A total of 8,153 eligible participants aged 60+ interviewed in up to six waves. Measurements Cognitive function and teeth number were measured at each interview. Cognitive function was measured by the Mini-Mental Status Examination (MMSE). Number of natural teeth was self-reported. Individuals with severe cognitive impairment were excluded. Covariates included demographic characteristics, adult socioeconomic status characteristics, childhood socioeconomic status, health conditions, and health behaviors. Linear mixed models were applied in the analysis. Results The mean teeth number at baseline was 17.5(SD = 0.1), and the mean of baseline cognitive function was 27.3(SD = 0.0). Cognitive function declined over time (β = -0.19, P < .001) after controlling covariates. But, regardless of time, more teeth were associated with better cognitive function (β = 0.01, P < .001). The interaction of teeth number and time was significant (β = 0.01, P < .001), suggesting that the participants who had more teeth showed a slower pace of cognitive decline over time than those with fewer teeth after controlling for other covariates. Conclusion This study showed that tooth loss was associated with cognitive decline among Chinese older adults. Further studies are needed to examine the linkages between cognitive decline and oral health status using clinical examination data. PMID:28158261

  16. Fish intake is associated with slower cognitive decline in Chinese older adults.

    PubMed

    Qin, Bo; Plassman, Brenda L; Edwards, Lloyd J; Popkin, Barry M; Adair, Linda S; Mendez, Michelle A

    2014-10-01

    Modifiable lifestyle changes, including dietary changes, could translate into a great reduction in the global burden of cognitive impairment and dementia. Few studies evaluated the benefits of fish intake for delaying cognitive decline, and no studies were conducted in a Chinese population, which may differ with respect to types, amounts, and correlates of fish consumption compared with Western populations. We hypothesized that higher consumption of fish would predict slower decline in cognitive function, independent of a wide range of potential confounders. This prospective cohort study comprised 1566 community-dwelling adults aged ≥ 55 y who completed a cognitive screening test at ≥2 waves of the China Health and Nutrition Survey in 1997, 2000, or 2004, with a mean follow-up of 5.3 y [age at entry (mean ± SD): 63 ± 6 y]. Diet was measured by 3-d 24-h recalls at baseline. Outcomes included repeated measures of global cognitive scores (baseline mean ± SD: 19 ± 6 points), composite cognitive Z-scores (standardized units), and standardized verbal memory scores (standardized units). Multivariable-adjusted linear mixed-effects models were used to evaluate the relation of fish intake with changes in cognitive scores. Age was found to significantly modify the association between fish consumption and cognitive change (P = 0.007). Among adults aged ≥ 65 y, compared with individuals who consumed <1 serving/wk (i.e., 100 g) fish, the mean annual rate of global cognitive decline was reduced by 0.35 point (95% CI: 0.13, 0.58) among those consuming ≥ 1 serving/wk, equivalent to the disparity associated with 1.6 y of age. Fish consumption was also associated with a slower decline in composite and verbal memory scores. No associations were observed among adults aged 55-64 y. Our findings suggest a potential role of fish consumption as a modifiable dietary factor to reduce the rate of cognitive decline in later life.

  17. 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.

  18. 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.

  19. Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research

    PubMed Central

    Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.

    2014-01-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  20. Literature review on the role of dietary protein and amino acids in cognitive functioning and cognitive decline.

    PubMed

    van de Rest, Ondine; van der Zwaluw, Nikita L; de Groot, Lisette C P G M

    2013-11-01

    As the population of elderly people is growing rapidly, the number of individuals with dementia and cognitive impairment is also increasing. One of the preventive measures against cognitive decline is diet and different dietary factors have already been investigated. This review provides an overview of studies on dietary protein and cognitive functioning and cognitive decline. Also studies on the individual amino acids that are related to brain function, tryptophan and tyrosine, are discussed. Overall, the role of dietary protein intake on cognitive functioning as well as cognitive decline has hardly been studied; we found eight observational studies and three intervention studies. More studies investigated the role of tryptophan (14 studies) and tyrosine (nine studies) in relation to cognitive functioning, but all these studies were performed in young adult populations and mostly under special conditions. Research in elderly populations, in particular, is warranted. Also more research is needed to come to definitive conclusions and specific recommendations regarding protein intake or intake of specific amino acids for maintaining optimal cognitive functioning.

  1. 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

  2. Cognitive decline and the PPAR-γ Pro12Ala genotype: variation by sex and ethnicity.

    PubMed

    A West, Nancy; Baxter, Judith; L Bryant, Lucinda; L Nelson, Tracy

    2017-01-06

    We investigated the association between the peroxisome proliferator-activated receptor (PPAR)-gamma Pro12Ala polymorphism and cognitive decline in older adults. Participants from a population-based cohort of older Hispanic and non-Hispanic white adults (n = 492) were administered the Mini Mental State Examination (MMSE), a multi-domain cognitive screening tool, and the Behavioral Dyscontrol Scale (BDS), a measure of executive cognitive function, at baseline and at follow-up, an average of 22 months later. Multiple linear regression was used to investigate the association between the two cognitive test scores and the Pro12Ala polymorphism. At baseline, presence of the Ala12 allele was not significantly associated with MMSE score (P = 0.62) nor with BDS score (P = 0.85). Heterogeneity was present for cognitive decline as measured by the MMSE among ethnic, sex and Ala12 allele status (P = 0.04 for three-way interaction term). Stratification by the cross-classification of sex and ethnicity revealed significantly greater declines in MMSE score among male Hispanic carriers of the Ala12 allele compared to male Hispanic non-carriers (decline = 4.0 versus 1.6 points; P = 0.02). A significant difference in decline between Ala12 carriers and non-carriers was not present among the other sex/ethnic groups. Carriers of the PPAR-γ Ala12 allele showed greater cognitive decline compared to non-carriers as detected by the MMSE but the risk varied across sex and ethnic groups. Male Ala12 carriers of Hispanic origin may be a high-risk group for cognitive decline.

  3. Effects of Comorbid Depression and Diabetes Mellitus on Cognitive Decline in Older Mexican Americans.

    PubMed

    Downer, Brian; Vickers, Benjamin N; Al Snih, Soham; Raji, Mukaila; Markides, Kyriakos S

    2016-01-01

    To assess the relationship between comorbid depression, diabetes mellitus (DM), and cognitive decline in Mexican Americans aged 65 and older. Retrospective cohort study with longitudinal analysis. Texas, New Mexico, Colorado, Arizona, and California. Hispanic Established Populations for the Epidemiologic Study of the Elderly. Cognition was assessed using the Mini-Mental State Examination (MMSE). Depression was defined as a score of 16 or greater on the Center for Epidemiologic Studies Depression Scale. DM was defined as according to self-reported history or taking insulin or oral hypoglycemic medication. Participants with depression and DM declined an average of 6.5 points on the MMSE; depression only, 4.4 points; DM only, 7.8 points; and neither condition, 4.2 points across the six examination waves. Participants with DM declined an average of 0.18 more points on the MMSE per year (P=.001) than those with neither DM nor depression, and those with comorbid DM and depression declined 0.25 more points per year (P=.002). Depression was associated with significantly greater cognitive decline (β^=-0.11, P=.05) after excluding participants with baseline cognitive impairment (MMSE score≤17). Participants with DM were 1.08 (95% CI=1.03-1.12) times as likely as those with neither DM nor depression, and those with comorbid DM and depression were 1.08 (95% CI=1.01-1.15) times as likely as those with neither DM nor depression to develop severe cognitive impairment per year. DM and comorbid depression and DM are risk factors for cognitive decline in older Mexican Americans. Interventions that reduce the prevalence of depression and DM in Mexican Americans may decrease the number of older adults who experience cognitive decline. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  4. 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.

  5. Racial differences in the progression of cognitive decline in Alzheimer disease.

    PubMed

    Barnes, Lisa L; Wilson, Robert S; Li, Yan; Aggarwal, Neelum T; Gilley, David W; McCann, Judith J; Evans, Denis A

    2005-11-01

    Alzheimer disease (AD) is the leading cause of dementia in older persons, but little is known about racial differences in its clinical manifestations. The purpose of the current study was to examine the association of race with rate of cognitive decline in AD. Older persons with clinically diagnosed AD were recruited from healthcare settings. At 6-month intervals for up to 4 years, they completed a battery of nine cognitive tests from which a previously established measure of global cognition was derived. Follow-up data were available on 452 participants (27.6% African American, 68.8% women), 88.1% of those eligible. A growth curve approach was used to estimate individual paths of change in global cognition. In a model that controlled for age and education, African Americans had a lower level of global cognition at baseline than non-African Americans, but declined at a 25% slower rate on average. In additional models, there was no indication that the association of race with cognitive decline varied by age, gender, or education. The rate of cognitive decline in AD appears to be slower in African Americans than non-African Americans.

  6. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline

    PubMed Central

    Tangney, Christine C.; Tang, Yuxiao; Evans, Denis A.; Morris, Martha Clare

    2009-01-01

    Background: In some prospective studies, associations of serum vitamin B12 and homocysteine concentrations with cognitive decline have been reported but few have examined the role of methylmalonic acid, a more specific marker of vitamin B12 deficiency than homocysteine. Objective: The aim of the study was to determine whether serum concentrations of vitamin B12 or selected metabolites are related to cognitive decline. Methods: A total of 516 subjects were selected in a stratified random sampling design from among Chicago Health and Aging Project participants for clinical evaluation. We used linear mixed models to examine the association of blood markers of vitamin B12 status to change in cognitive scores over 6 years. Cognitive function was assessed every 3 years and measured as the sum of standardized scores on four tests. Results: Probable vitamin B12 deficiency was observed in 14.2% of the sample. Elevated serum concentrations of homocysteine were present in 19.2% of subjects, and of methylmalonic acid, in 36.4%. Higher serum methylmalonic acid concentrations were predictive of faster rates of cognitive decline (β = −0.00016, SE = 0.0001, p = 0.004) and higher serum vitamin B12 concentrations were associated with slower rates of cognitive decline (β = +0.00013, SE < 0.0001, p = 0.005) in multivariable adjusted mixed models. Serum concentrations of homocysteine had no relationship to cognitive decline. Conclusions: Serum methylmalonic acid and vitamin B12 concentrations may be the more important risk factors for cognitive decline when compared to serum homocysteine concentrations, particularly in older populations exposed to food fortification and possible supplements containing folic acid. GLOSSARY CHAP = Chicago Health and Aging Project; CI = confidence interval; FFQ = food frequency questionnaire; NHANES = National Health and Nutrition Examination Survey; OR = odds ratio. PMID:19171834

  7. Cognitive Function and Health Literacy Decline in a Cohort of Aging English Adults.

    PubMed

    Kobayashi, Lindsay C; Wardle, Jane; Wolf, Michael S; von Wagner, Christian

    2015-07-01

    Low health literacy is common among aging patients and is a risk factor for morbidity and mortality. We aimed to describe health literacy decline during aging and to investigate the roles of cognitive function and decline in determining health literacy decline. Data were from 5,256 non-cognitively impaired adults aged ≥ 52 years in the English Longitudinal Study of Ageing. Health literacy was assessed using a four-item reading comprehension assessment of a fictitious medicine label, and cognitive function was assessed in a battery administered in-person at baseline (2004-2005) and at follow-up (2010-2011). Overall, 19.6% (1,032/5,256) of participants declined in health literacy score over the follow-up. Among adults aged ≥ 80 years at baseline, this proportion was 38.2% (102/267), compared to 14.8% (78/526) among adults aged 52-54 years (OR = 3.21; 95% CI: 2.26-4.57). Other sociodemographic predictors of health literacy decline were: male sex (OR = 1.20; 95% CI: 1.04-1.38), non-white ethnicity (OR = 2.42; 95% CI: 1.51-3.89), low educational attainment (OR = 1.58; 95% CI: 1.29-1.95 for no qualifications vs. degree education), and low occupational class (OR = 1.67; 95% CI: 1.39-2.01 for routine vs. managerial occupations). Higher baseline cognitive function scores protected against health literacy decline, while cognitive decline (yes vs. no) predicted decline in health literacy score (OR = 1.59; 95% CI: 1.35-1.87 for memory decline and OR = 1.56; 95% CI: 1.32-1.85 for executive function decline). Health literacy decline appeared to increase with age, and was associated with even subtle cognitive decline in older non-impaired adults. Striking social inequalities were evident, whereby men and those from minority and deprived backgrounds were particularly vulnerable to literacy decline. Health practitioners must be able to recognize limited health literacy to ensure that clinical demands match the literacy skills of diverse patients.

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

    PubMed Central

    Moatti, Jean-Paul; Marmot, Michael G.; Kivimaki, Mika

    2017-01-01

    Background 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. Methods and findings 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

  9. 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

  10. 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

  11. Community-level education accelerates the cultural evolution of fertility decline.

    PubMed

    Colleran, Heidi; Jasienska, Grazyna; Nenko, Ilona; Galbarczyk, Andrzej; Mace, Ruth

    2014-03-22

    Explaining why fertility declines as populations modernize is a profound theoretical challenge. It remains unclear whether the fundamental drivers are economic or cultural in nature. Cultural evolutionary theory suggests that community-level characteristics, for example average education, can alter how low-fertility preferences are transmitted and adopted. These assumptions have not been empirically tested. Here, we show that community-level education accelerates fertility decline in a way that is neither predicted by individual characteristics, nor by the level of economic modernization in a population. In 22 high-fertility communities in Poland, fertility converged on a smaller family size as average education in the community increased-indeed community-level education had a larger impact on fertility decline than did individual education. This convergence was not driven by educational levels being more homogeneous, but by less educated women having fewer children than expected, and more highly educated social networks, when living among more highly educated neighbours. The average level of education in a community may influence the social partners women interact with, both within and beyond their immediate social environments, altering the reproductive norms they are exposed to. Given a critical mass of highly educated women, less educated neighbours may adopt their reproductive behaviour, accelerating the pace of demographic transition. Individual characteristics alone cannot capture these dynamics and studies relying solely on them may systematically underestimate the importance of cultural transmission in driving fertility declines. Our results are inconsistent with a purely individualistic, rational-actor model of fertility decline and suggest that optimization of reproduction is partly driven by cultural dynamics beyond the individual.

  12. Community-level education accelerates the cultural evolution of fertility decline

    PubMed Central

    Colleran, Heidi; Jasienska, Grazyna; Nenko, Ilona; Galbarczyk, Andrzej; Mace, Ruth

    2014-01-01

    Explaining why fertility declines as populations modernize is a profound theoretical challenge. It remains unclear whether the fundamental drivers are economic or cultural in nature. Cultural evolutionary theory suggests that community-level characteristics, for example average education, can alter how low-fertility preferences are transmitted and adopted. These assumptions have not been empirically tested. Here, we show that community-level education accelerates fertility decline in a way that is neither predicted by individual characteristics, nor by the level of economic modernization in a population. In 22 high-fertility communities in Poland, fertility converged on a smaller family size as average education in the community increased—indeed community-level education had a larger impact on fertility decline than did individual education. This convergence was not driven by educational levels being more homogeneous, but by less educated women having fewer children than expected, and more highly educated social networks, when living among more highly educated neighbours. The average level of education in a community may influence the social partners women interact with, both within and beyond their immediate social environments, altering the reproductive norms they are exposed to. Given a critical mass of highly educated women, less educated neighbours may adopt their reproductive behaviour, accelerating the pace of demographic transition. Individual characteristics alone cannot capture these dynamics and studies relying solely on them may systematically underestimate the importance of cultural transmission in driving fertility declines. Our results are inconsistent with a purely individualistic, rational-actor model of fertility decline and suggest that optimization of reproduction is partly driven by cultural dynamics beyond the individual. PMID:24500166

  13. Caffeine and cognitive decline in elderly women at high vascular risk

    PubMed Central

    Vercambre, Marie-Noël; Berr, Claudine; Ritchie, Karen; Kang, Jae H.

    2013-01-01

    Background Persons with vascular disorders are at higher risk of cognitive decline. Objective To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk. Methods We included 2475 women aged 65+ years in the Women’s Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995–1996) using a validated 116 item-food frequency questionnaire. From 1998–2000 to 2005–2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake. Results We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend=0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (> 371 versus < 30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p=0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend=0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02). Conclusions Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders. PMID:23422357

  14. Caffeine and cognitive decline in elderly women at high vascular risk.

    PubMed

    Vercambre, Marie-Noël; Berr, Claudine; Ritchie, Karen; Kang, Jae H

    2013-01-01

    Persons with vascular disorders are at higher risk of cognitive decline. To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk. We included 2,475 women aged 65+ years in the Women's Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995-1996) using a validated 116 item-food frequency questionnaire. From 1998-2000 to 2005-2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory, and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health, and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake. We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend = 0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (>371 versus <30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p = 0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend = 0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02). Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders.

  15. Differing effects of education on cognitive decline in diverse elders with low versus high educational attainment.

    PubMed

    Zahodne, Laura B; Stern, Yaakov; Manly, Jennifer J

    2015-07-01

    In light of growing debate over whether and how early life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. Older adults (N = 3,435) in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. More years of education were associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. Although having additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., 9 years and beyond) is associated with higher income, which may influence late-life cognitive health through multiple, nonmutually exclusive pathways. (c) 2015 APA, all rights reserved).

  16. Differing effects of education on cognitive decline in diverse elders with low versus high educational attainment

    PubMed Central

    Zahodne, Laura B.; Stern, Yaakov; Manly, Jennifer J.

    2014-01-01

    Objective In light of growing debate over whether and how early-life educational experiences alter late-life cognitive trajectories, this study sought to more thoroughly investigate the relationship between educational attainment and rates of late-life cognitive decline in a racially, ethnically, and educationally diverse population. Method 3,435 older adults in the community-based Washington Heights-Inwood Columbia Aging Project were administered neuropsychological tests of memory, language, visuospatial function, and processing speed at approximate 24-month intervals for up to 18 years. Second-order latent growth curves estimated direct and indirect (through income) effects of educational attainment on rates of global cognitive decline separately in individuals with low (0-8 years) and high (9-20 years) educational attainment. Results More years of education was associated with higher cognitive level and slower cognitive decline in individuals with low or high educational attainment. The association between having more than 9 years of education and exhibiting slower cognitive decline was fully mediated by income. While additional years of education up to 8 years was also associated with higher income, this did not explain associations between education and cognitive change in the low-education group. Conclusions Early education (i.e., up to 8 years) may promote aspects of development during a sensitive period of childhood that protect against late-life cognitive decline independent of income. In contrast, later education (i.e., beyond 9 years) is associated with higher income, which may influence late-life cognitive health through multiple, non-mutually exclusive pathways. PMID:25222199

  17. Vestibular Performance During High-Acceleration Stimuli Correlates with Clinical Decline in SCA6.

    PubMed

    Huh, Young Eun; Kim, Ji-Soo; Kim, Hyo-Jung; Park, Seong-Ho; Jeon, Beom Seok; Kim, Jong-Min; Cho, Jin Whan; Zee, David S

    2015-06-01

    In spinocerebellar ataxia type 6 (SCA6), the vestibular dysfunction and its correlation with other clinical parameters require further exploration. We determined vestibular responses over a broad range of stimulus acceleration in 11 patients with SCA6 (six men, age range=33-72 years, mean age±SD=59±12 years) using bithermal caloric irrigations, rotary chair, and head impulse tests. Correlations were also pursued among disability scores, as measured using the International Cooperative Ataxia Rating Scale, disease duration, age at onset, cytosine-adenine-guanine (CAG) repeat length, and the gain of the vestibulo-ocular reflex (VOR). In response to relatively low-acceleration, low-frequency rotational and bithermal caloric stimuli, the VOR gains were normal or increased regardless of the severity of disease. On the other hand, with relatively high-acceleration, high-frequency head impulses, there was a relative increase in gain in the mildly affected patients and a decrease in gain in the more severely affected patients and gains were negatively correlated with the severity of disease (Spearman correlation, R=-0.927, p<0.001). Selective decrease of the vestibular responses during high-acceleration, high-frequency stimuli may be ascribed to degeneration of either the flocculus or vestibular nuclei. The performance of the VOR during high-acceleration, high-frequency head impulses may be a quantitative indicator of clinical decline in SCA6.

  18. The myth of cognitive decline: non-linear dynamics of lifelong learning.

    PubMed

    Ramscar, Michael; Hendrix, Peter; Shaoul, Cyrus; Milin, Petar; Baayen, Harald

    2014-01-01

    As adults age, their performance on many psychometric tests changes systematically, a finding that is widely taken to reveal that cognitive information-processing capacities decline across adulthood. Contrary to this, we suggest that older adults'; changing performance reflects memory search demands, which escalate as experience grows. A series of simulations show how the performance patterns observed across adulthood emerge naturally in learning models as they acquire knowledge. The simulations correctly identify greater variation in the cognitive performance of older adults, and successfully predict that older adults will show greater sensitivity to fine-grained differences in the properties of test stimuli than younger adults. Our results indicate that older adults'; performance on cognitive tests reflects the predictable consequences of learning on information-processing, and not cognitive decline. We consider the implications of this for our scientific and cultural understanding of aging. Copyright © 2013 Cognitive Science Society, Inc.

  19. Trajectories of cognitive decline following dementia onset: what accounts for variation in progression?

    PubMed

    MacDonald, Stuart W S; Karlsson, Sari; Fratiglioni, Laura; Bäckman, Lars

    2011-01-01

    Delineating the natural history of dementia progression has important clinical implications, including reducing caregiver burden and targeting effective drug trials. We examined whether trajectories of cognitive change differed reliably after diagnosis, and whether diverse predictors of such differences (demographic, psychological, biological, genetic, social) could be identified. Cognitive change was examined for incident dementia cases (mild: n = 156; moderate: n = 77; severe: n = 73) and controls (n = 249) from the Kungsholmen Project, a community-based study of adults 75 years and older. For those with dementia, total variance attributed to between-person differences in cognitive decline was modest and linked to but a single predictor (history of cardiovascular disease). Although less variance in cognitive decline was observed for the similarly aged controls, numerous significant predictors of these differences were identified. The neurodegenerative process underlying dementia overshadows formerly significant predictors of cognitive change. Copyright © 2011 S. Karger AG, Basel.

  20. 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

  1. Predictors of Cognitive Decline in Older Adult Type 2 Diabetes from the Veterans Affairs Diabetes Trial.

    PubMed

    Zimering, Mark B; Knight, Jeffrey; Ge, Ling; Bahn, Gideon

    2016-01-01

    Cognitive decline disproportionately affects older adult type 2 diabetes. We tested whether randomized intensive (INT) glucose-lowering reduces the rate(s) of cognitive decline in adults with advanced type 2 diabetes (mean: age, 60 years; diabetes duration, 11 years) from the Veterans Affairs Diabetes Trial. A battery of neuropsychological tests [digit span, digit symbol substitution (DSym), and Trails-making Test-Part B (TMT-B)] was administered at baseline in ~1700 participants and repeated at year 5. Thirty-seven risk factors were evaluated as predictors of cognitive decline in multivariable regression analyses. The mean age-adjusted DSym or TMT-B declined significantly in all study participants (P < 0.001). Randomized INT glucose-lowering did not significantly alter the rate of cognitive decline. The final model of risk factors associated with 5-year decline in age-adjusted TMT-B included as significant predictors: longer baseline diabetes duration (beta = -0.028; P = 0.0057), lower baseline diastolic blood pressure (BP; beta = 0.028; P = 0.002), and baseline calcium channel blocker medication use (beta = -0.639; P < 0.001). Higher baseline pulse pressure was significantly associated with decline in age-adjusted TMT-B suggesting a role for both higher systolic and lower diastolic BPs. Baseline thiazide diuretic use (beta = -0.549; P = 0.015) was an additional significant predictor of 5-year decline in age-adjusted digit symbol score. Post-baseline systolic BP-lowering was significantly associated (P < 0.001) with decline in TMT-B performance. There was a significant inverse association between post-baseline plasma triglyceride-lowering (P = 0.045) and decline in digit symbol substitution task performance. A 5-year period of randomized INT glucose-lowering did not significantly reduce the rate of cognitive decline in older-aged adults with type 2 diabetes. Systolic and diastolic BPs as well as plasma triglycerides

  2. Macrophage inhibitory cytokine-1 is associated with cognitive impairment and predicts cognitive decline - the Sydney Memory and Aging Study.

    PubMed

    Fuchs, Talia; Trollor, Julian N; Crawford, John; Brown, David A; Baune, Bernhard T; Samaras, Katherine; Campbell, Lesley; Breit, Samuel N; Brodaty, Henry; Sachdev, Perminder; Smith, Evelyn

    2013-10-01

    Higher levels of macrophage inhibitory cytokine-1, also known as growth differentiation factor 15 (MIC-1/GDF15), are associated with adverse health outcomes and all-cause mortality. The aim of this study was to examine the relationships between MIC-1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70-90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C-reactive protein, tumor necrosis factor-α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC-1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross-sectional associations were found between MIC-1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC-1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC-1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC-1/GDF15 cutoff values associated with cognitive decline and showed that a MIC-1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC-1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

  3. 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

  4. Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.

    PubMed

    Feng, Xiaomei; Degos, Vincent; Koch, Lauren G; Britton, Steven L; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn

    2013-05-01

    Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.

  5. Surgery Results in Exaggerated and Persistent Cognitive Decline in a Rat Model of the Metabolic Syndrome

    PubMed Central

    Feng, Xiaomei; Degos, Vincent; Koch, Lauren G.; Britton, Steven L.; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn

    2017-01-01

    Background Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. Methods In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. Results On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Conclusion Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients. PMID:23353794

  6. The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions

    PubMed Central

    VanGuilder, Heather D.; Freeman, Willard M.

    2011-01-01

    Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed. PMID:21647399

  7. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

    PubMed

    Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

    2015-06-15

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

  8. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  9. Lower cerebral blood flow is associated with faster cognitive decline in Alzheimer's disease.

    PubMed

    Benedictus, Marije R; Leeuwis, Annebet E; Binnewijzend, Maja A A; Kuijer, Joost P A; Scheltens, Philip; Barkhof, Frederik; van der Flier, Wiesje M; Prins, Niels D

    2017-03-01

    To determine whether lower cerebral blood flow (CBF) is associated with faster cognitive decline in patients with Alzheimer's disease (AD). We included 88 patients with dementia due to AD from the Amsterdam Dementia Cohort. Mean follow-up was 2 ± 1 years. Linear mixed models were used to determine associations of lower whole brain and regional pseudo-continuous arterial spin labelling measured CBF with rate of cognitive decline as measured with repeated mini-mental state examination (MMSE). Model 1 was adjusted for age, sex, and education. Model 2 was additionally adjusted for normalized gray matter volume, medial temporal lobe atrophy, white matter hyperintensities, microbleeds, and lacunes. Analyses were repeated after partial volume correction (PVC) of CBF. Statistical significance was set at p ≤ 0.05. Patients were 65 ± 7 years old, 44 (50 %) were women, and mean baseline MMSE was 22 ± 4. Annual decline (β[SE]) on the MMSE was estimated at -2.11 (0.25) points per year. Lower whole brain (β[SE]-0.50[0.25]; p ≤ 0.05) and parietal (β[SE]-0.59[0.25]; p < 0.05) CBF were associated with faster cognitive decline. PVC cortical CBF was not associated with cognitive decline. Lower CBF, in particular in the posterior brain regions, may have value as a prognostic marker for rate of cognitive decline in AD. • In AD, lower CBF is associated with more rapid cognitive decline. • Decreasing CBF does not reach a plateau early in AD. • PcASL-CFB has additive value to conventional structural MRI measures in AD.

  10. Hypercholesterolemia in elders is associated with slower cognitive decline: a prospective, population-based study (NEDICES).

    PubMed

    Benito-León, Julián; Vega-Quiroga, Saturio; Villarejo-Galende, Alberto; Bermejo-Pareja, Félix

    2015-03-15

    Studies investigating the association between hypercholesterolemia in the elderly and cognitive decline report discrepant outcomes. We determined in a prospective population-based cohort (NEDICES) in elders whether hypercholesterolemia was associated with slower cognitive decline. Participants were evaluated at baseline and 3 years later. Baseline demographic variables were recorded. Hypercholesterolemia was defined by total cholesterol of >200mg/dl or current use of lipid-lowering drugs. At baseline and at follow-up, a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered. The final sample, 2015 participants (72.9 ± 6.1 years), comprised 1166 (57.9%) hypercholesterolemic and 849 (42.1%) non-hypercholesterolemic participants (reference category). The mean follow-up was 3.4 ± 0.5 years. During the three year follow-up period, the 37-MMSE declined by 0.7 ± 4.3 points (median=0 point) in non-hypercholesterolemic participants vs. 0.3 ± 3.9 points in hypercholesterolemic participants (median=0 points) (Mann-Whitney test, p=0.007). In analyses adjusted for baseline age and other potential confounders, this difference remained robust. We also assessed the cognitive decline per unit time (i.e., the rate of cognitive decline). The rate of cognitive decline was 0.2 ± 1.3 (median=0.0) points/year for non-hypercholesterolemic participants and 0.1 ± 1.2 (median=0.0) points/year for hypercholesterolemic participants (Mann-Whitney test, p=0.028). In this prospective population-based cohort study, cognitive test scores among hypercholesterolemic elders declined more slowly than observed in their non-hypercholesterolemic counterparts. Additional studies are needed to confirm these results. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease.

    PubMed

    Weintraub, Daniel; Dietz, Nicole; Duda, John E; Wolk, David A; Doshi, Jimit; Xie, Sharon X; Davatzikos, Christos; Clark, Christopher M; Siderowf, Andrew

    2012-01-01

    Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = -0.31, P = 0.007), including in non-demented patients (β = -0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal-temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline in

  12. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China

    PubMed Central

    Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-hua; Yang, Ce-ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

    2016-01-01

    Abstract Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China. We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year. The mean age at diagnosis was 72.0 ± 10.0 years (range 38–96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11–2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09–3.06). Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID:27367978

  13. Early life origins cognitive decline: findings in elderly men in the Helsinki Birth Cohort Study.

    PubMed

    Raikkonen, Katri; Kajantie, Eero; Pesonen, Anu-Katriina; Heinonen, Kati; Alastalo, Hanna; Leskinen, Jukka T; Nyman, Kai; Henriksson, Markus; Lahti, Jari; Lahti, Marius; Pyhälä, Riikka; Tuovinen, Soile; Osmond, Clive; Barker, David J P; Eriksson, Johan G

    2013-01-01

    To examine whether the adverse effects of slow prenatal and postnatal growth on cognitive function persist to old age and predict age related cognitive decline. A longitudinal birth cohort study of men born in Helsinki, Finland 1934-44. Nine-hundred-thirty-one men of the Helsinki Birth Cohort Study, with detailed data on growth from birth to adulthood, aged 20.1 (SD = 1.4) at the first and 67.9 (SD = 2.5) years at the second cognitive testing. The Finnish Defense Forces Basic Intellectual Ability Test assessed twice over nearly five decades apart. Lower weight, length and head circumference at birth were associated with lower cognitive ability at 67.9 years (1.04-1.55 points lower ability per each standard deviation [SD] unit decrease in body size, 95% Confidence Interval [95%CI]: 0.05 to 2.72) and with cognitive decline after 20.1 years (0.07-0.11 SD decline over time per each SD decrease in body size, 95%CI:0.00 to 0.19). Men who were born larger were more likely to perform better in the cognitive ability test over time (1.22-1.43 increase in odds to remain in the top relative to the lower two thirds in ability over time per each SD increase in body size, 95%CI:1.04 to 1.79) and were more resilient to cognitive decline after 20.1 years (0.69 to 0.76 decrease in odds to decline from than remain in the top third of ability over time per each SD increase in body size, 95%CI:0.49 to 0.99). Slower growth between birth and two years in weight, height and body mass index was associated with lower cognitive ability at 67.9 years, but not with cognitive decline. Poorer lifetime cognitive ability is predicted by slower growth before and after birth. In predicting resilience to age related cognitive decline, the period before birth seems to be more critical.

  14. Association of Lifetime Intellectual Enrichment with Cognitive Decline in the Older Population

    PubMed Central

    Vemuri, Prashanthi; Lesnick, Timothy G.; Przybelski, Scott A.; Machulda, Mary; Knopman, David S.; Mielke, Michelle M.; Roberts, Rosebud O.; Geda, Yonas E.; Rocca, Walter A.; Petersen, Ronald C.; Jack, Clifford R.

    2014-01-01

    IMPORTANCE Intellectual lifestyle enrichment throughout life is increasingly viewed as a protective strategy against commonly observed cognitive decline in the elderly. OBJECTIVE To investigate the association of lifetime intellectual enrichment with baseline cognitive performance and rate of cognitive decline in a non-demented elderly population and to estimate difference (in years) associated with lifetime intellectual enrichment to the onset of cognitive impairment. DESIGN, SETTING, PARTICIPANTS Prospective analysis of subjects enrolled in the Mayo Clinic Study of Aging (MCSA), a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We studied 1995 non-demented (1718 cognitively normal, 277 MCI) participants in MCSA who completed intellectual lifestyle measures at baseline and underwent at least one follow-up visit. MAIN OUTCOMES AND MEASURES We studied the effect of lifetime intellectual enrichment by separating the variables into two non-overlapping principal components: education/occupation-score and mid/late-life cognitive activity measure based on self-report questionnaires. A global cognitive Z-score served as our summary cognition measure. We used linear mixed-effects models to investigate the associations of demographic and intellectual enrichment measures with global cognitive Z-score trajectories. RESULTS Baseline cognitive performance was lower in older subjects and in those with lower education/occupation, lower mid/late-life cognitive activity, apolipoprotein E4 (APOE) genotype, and in men. The interaction between the two intellectual enrichment measures was significant such that the beneficial effect of mid/late-life cognitive activity on baseline cognitive performance was reduced with increasing education/occupation. Only baseline age, mid/late-life cognitive activity, and APOE4 genotype were significantly associated with longitudinal change in cognitive performance from baseline. For APOE4 carriers with high

  15. Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation

    SciTech Connect

    Mogi, Masaki; Li Jianmei; Tsukuda, Kana; Iwanami, Jun; Min, Li-Juan; Sakata, Akiko; Fujita, Teppei; Iwai, Masaru; Horiuchi, Masatsugu

    2008-10-24

    Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.

  16. 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.

  17. VISIT-TO-VISIT VARIABILITY IN BLOOD PRESSURE IS RELATED TO LATE-LIFE COGNITIVE DECLINE

    PubMed Central

    Qin, Bo; Viera, Anthony J.; Muntner, Paul; Plassman, Brenda L.; Edwards, Lloyd J.; Adair, Linda S.; Popkin, Barry M.; Mendez, Michelle A.

    2016-01-01

    The association between visit-to-visit variability of blood pressure (BP) and cognitive decline over time remains incompletely understood in a general population of older adults. We assessed the hypothesis that higher visit-to-visit variability in BP, but not mean BP, would be associated with faster decline in cognitive function among community-dwelling older adults. This prospective cohort study comprised 976 adults who had 3 or 4 visits with BP measurements as part of the China Health and Nutrition Survey from 1991, up to their first cognitive tests, and completed cognitive screening tests at 2 or more visits in 1997, 2000 or 2004. Visit-to visit BP variability was expressed as the standard deviation (SD), coefficient of variation or as the variation independent of mean BP across visits conducted at a mean interval of 3.2y. Mean (SD) age at the first cognitive test was 64 (6)y. Using multivariable-adjusted linear mixed-effects models, we found higher visit-to-visit variability in systolic BP, but not mean systolic BP, was associated with a faster decline of cognitive function (adjusted mean difference [95% CI] for high vs. low tertile of SD variability: standardized composite scores −0.038 standardized units (SU)/y [−0.066, −0.009] and verbal memory −0.041 SU/y [−0.075 to −0.008]). Higher visit-to-visit variability in diastolic BP was associated with a faster decline of cognitive function, independent of mean diastolic BP, among adults 55–64y but not those ≥ 65y. Our results suggest that higher long-term BP visit-to-visit variability is associated with a faster rate of cognitive decline among older adults. PMID:27217401

  18. Amyloid-β, anxiety, and cognitive decline in preclinical Alzheimer disease: a multicenter, prospective cohort study.

    PubMed

    Pietrzak, Robert H; Lim, Yen Ying; Neumeister, Alexander; Ames, David; Ellis, Kathryn A; Harrington, Karra; Lautenschlager, Nicola T; Restrepo, Carolina; Martins, Ralph N; Masters, Colin L; Villemagne, Victor L; Rowe, Christopher C; Maruff, Paul

    2015-03-01

    Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms. To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD. In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics. Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability. A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not

  19. The LonDownS adult cognitive assessment to study cognitive abilities and decline in Down syndrome

    PubMed Central

    2016-01-01

    Background: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with an ultra-high risk of developing Alzheimer’s disease. However, there is individual variability in the onset of clinical dementia and in baseline cognitive abilities prior to decline, particularly in memory, executive functioning, and motor coordination. The LonDownS Consortium aims to determine risk and protective factors for the development of dementia and factors relating to cognitive abilities in people with DS. Here we describe our cognitive test battery and related informant measures along with reporting data from our baseline cognitive and informant assessments. Methods: We developed a cognitive test battery to assess general abilities, memory, executive function, and motor coordination abilities in adults with DS, with informant ratings of similar domains also collected, designed to allow for data on a broad range of participants. Participants (n=305) had a range of ages and abilities, and included adults with and without a clinical diagnosis of dementia. Results: Results suggest the battery is suitable for the majority of adults with DS, although approximately half the adults with dementia were unable to undertake any cognitive task. Many test outcomes showed a range of scores with low floor and ceiling effects. Non-verbal age-adjusted IQ scores had lower floor effects than verbal IQ scores. Before the onset of any cognitive decline, females aged 16-35 showed better verbal abilities compared to males. We also identified clusters of cognitive test scores within our battery related to visuospatial memory, motor coordination, language abilities, and processing speed / sustained attention. Conclusions: Our further studies will use baseline and longitudinal assessments to explore factors influencing cognitive abilities and cognitive decline related to ageing and onset of dementia in adults with DS. PMID:28018980

  20. Greater Cognitive Decline with Aging among Elders with High Serum Concentrations of Organochlorine Pesticides

    PubMed Central

    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

  1. Deep brain stimulation and cognitive decline in Parkinson's disease: The predictive value of electroencephalography.

    PubMed

    Markser, A; Maier, Franziska; Lewis, C J; Dembek, T A; Pedrosa, D; Eggers, C; Timmermann, L; Kalbe, E; Fink, G R; Burghaus, Lothar

    2015-10-01

    Some Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS) develop new-onset cognitive decline. We examined whether clinical EEG recordings can be used to predict cognitive deterioration in PD patients undergoing STN-DBS. In this retrospective study, we used the Grand Total EEG (GTE)-score (short and total) to evaluate pre- and postoperative EEGs. In PD patients undergoing STN-DBS (N = 30), cognitive functioning was measured using Mini-Mental State Test and DemTect before and after surgery. Severity of motor impairment was assessed using the Unified Parkinson's Disease Rating Scale-III. Patients were classified into patients with or without cognitive decline after STN-DBS surgery. Epidemiological data, pre- and postoperative EEG recordings as well as neuropsychological and neurological data, electrode positions and the third ventricle width were compared. A logistic regression model was used to identify predictors of cognitive decline. Motor deficits significantly improved from pre- to post-surgery, while the mean GTE-scores increased significantly. Six patients developed cognitive deterioration 4-12 months postoperatively. These patients had significantly higher preoperative GTE-scores than patients without cognitive deterioration, although preoperative cognitive functioning was comparable. Electrode positions, brain atrophy and neurological data did not differ between groups. Logistic regression analysis identified the GTE-score as a significant predictor of postoperative cognitive deterioration. Data suggest that the preoperative GTE-score can be used to identify PD patients that are at high risk for developing cognitive deterioration after STN-DBS surgery even though their preoperative cognitive state was normal.

  2. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline.

    PubMed

    Leal, Stephanie L; Landau, Susan M; Bell, Rachel K; Jagust, William J

    2017-02-08

    The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer's disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baseline was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.

  3. Metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline

    PubMed Central

    Wang, Maggie; Norman, Jennifer E; Srinivasan, Vivek J; Rutledge, John C

    2016-01-01

    White Matter Disease is increasingly being recognized as an important cause of cognitive decline and dementia. Various investigations have linked chronic diet-related conditions to the development of white matter lesions, which appear as white matter hyperintensities on T2-weighted magnetic resonance imaging (MRI) scans of the brain. Thus, it can be postulated that the metabolic, inflammatory, and microvascular changes accompanying a western diet, hyperlipidemia, hypertension, and diabetes mellitus type II (DMII) are potential mediators in the development and progression of white matter disease, which in turn contributes to the development and progression of cognitive decline. This review will examine evidence for potential metabolic, inflammatory, and microvascular determinants of white matter disease and cognitive decline. Specifically, we will focus on the effects of altered insulin signaling in diabetes, obesity-induced oxidative stress, neuroinflammation, arterial stiffness due to hypertension, ischemia secondary to cerebral small vessel disease, and blood brain barrier disturbances. PMID:28078193

  4. Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline

    DOE PAGES

    Leal, Stephanie L.; Landau, Susan M.; Bell, Rachel K.; ...

    2017-02-08

    The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer’s disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental and could be one factor that drives Aβ deposition. To test this model, we examined the relationship between hippocampal activity during a memory task using fMRI and subsequent longitudinal change in Aβ using PIB-PET imaging in cognitively normal older adults. We found that greater hippocampal activation at baselinemore » was associated with increased Aβ accumulation. Furthermore, increasing Aβ accumulation mediated the influence of hippocampal activation on declining memory performance, demonstrating a crucial role of Aβ in linking hippocampal activation and memory. These findings support a model linking increased hippocampal activation to subsequent Aβ deposition and cognitive decline.« less

  5. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  6. Age-related decline in cognitive control: the role of fluid intelligence and processing speed.

    PubMed

    Manard, Marine; Carabin, Delphine; Jaspar, Mathieu; Collette, Fabienne

    2014-01-08

    Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment.

  7. Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

    PubMed Central

    Desler, Claus; Frederiksen, Jane H.; Angleys, Maria; Maynard, Scott; Keijzers, Guido; Fagerlund, Birgitte; Mortensen, Erik Lykke; Osler, Merete; Lauritzen, Martin; Bohr, Vilhelm A.; Rasmussen, Lene Juel

    2016-01-01

    Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer’s disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD. PMID:26408413

  8. Linking cognitive and visual perceptual decline in healthy aging: The information degradation hypothesis.

    PubMed

    Monge, Zachary A; Madden, David J

    2016-10-01

    Several hypotheses attempt to explain the relation between cognitive and perceptual decline in aging (e.g., common-cause, sensory deprivation, cognitive load on perception, information degradation). Unfortunately, the majority of past studies examining this association have used correlational analyses, not allowing for these hypotheses to be tested sufficiently. This correlational issue is especially relevant for the information degradation hypothesis, which states that degraded perceptual signal inputs, resulting from either age-related neurobiological processes (e.g., retinal degeneration) or experimental manipulations (e.g., reduced visual contrast), lead to errors in perceptual processing, which in turn may affect non-perceptual, higher-order cognitive processes. Even though the majority of studies examining the relation between age-related cognitive and perceptual decline have been correlational, we reviewed several studies demonstrating that visual manipulations affect both younger and older adults' cognitive performance, supporting the information degradation hypothesis and contradicting implications of other hypotheses (e.g., common-cause, sensory deprivation, cognitive load on perception). The reviewed evidence indicates the necessity to further examine the information degradation hypothesis in order to identify mechanisms underlying age-related cognitive decline. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. 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.

  10. Temporal cognitive decline associated with exposure to infectious agents in a population-based, aging cohort

    PubMed Central

    Nimgaonkar, Vishwajit L; Yolken, Robert H; Wang, Tianxiu; Chang, Chung-Chou H.; McClain, Lora; McDade, Eric; Snitz, Beth E.; Ganguli, Mary

    2015-01-01

    Background Numerous cross-sectional studies have related exposure to neurotropic infectious agents with cognitive dysfunction in older adults, but the temporal sequence is uncertain. Methods In a representative, well-characterized, population-based aging cohort, we determined whether the temporal trajectories of multiple cognitive domains are associated with exposure to cytomegalovirus (CMV), Herpes Simplex virus, type 1 (HSV-1), Herpes Simplex virus, type 2 (HSV-2) or Toxoplasma gondii (TOX). Complex attention, executive functions, memory, language, and visuospatial function were assessed annually for five years among consenting individuals. Study entry IgG antibody titers indexing exposure to each infectious agent were examined in relation to slopes of subsequent temporal cognitive decline using multiple linear regressions adjusted for potential confounders. Results The IgG levels for HSV-2 were significantly associated with baseline cognitive domain scores (N=1022 participants). Further, the IgG levels for HSV-2, TOX and CMV, but not HSV-1 were significantly associated with greater temporal cognitive decline that varied by type of infection. Conclusions Exposure to CMV, HSV-2, or TOX is associated with cognitive deterioration in older individuals, independent of general age related variables. An increased understanding of the role of infectious agents in cognitive decline may lead to new methods for its prevention and treatment. PMID:26710257

  11. Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer's disease, through angiotensin II.

    PubMed

    Nakagawa, Takashi; Hasegawa, Yu; Uekawa, Ken; Kim-Mitsuyama, Shokei

    2017-01-01

    Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding an adenine-containing diet and the effect on cognitive function was compared between both strains. There was no significant difference regarding the severity of CKD induced by adenine between the strains. In 5XFAD mice, the CKD group exhibited significant cognitive impairment while the control group (control diet-fed group) did not, as evidenced by a passive avoidance test. On the other hand, in wild-type mice, neither the CKD group nor the control group showed cognitive impairment. Thus, CKD itself appears to accelerate cognitive impairment in AD mice. (2) We also examined the effect of olmesartan, an angiotensin II receptor blocker, on 5XFAD mice with CKD to elucidate the potential involvement of angiotensin II. As evidenced by the findings of the water maze test, olmesartan treatment significantly ameliorated the impairment of spatial learning and memory function induced by CKD in 5XFAD mice. Olmesartan treatment significantly ameliorated blood-brain barrier (BBB) disruption induced by CKD in 5XFAD mice. Furthermore, olmesartan reduced hippocampal oxidative stress in 5XFAD with CKD to similar levels to the control group of 5XFAD fed standard diet. Hence, the amelioration of CKD-induced cognitive impairment in 5XFAD mice by olmesartan appears to be mediated by the suppression of BBB disruption or oxidative stress. In conclusion, we obtained the evidence suggesting that CKD itself accelerates cognitive impairment in AD mice, through angiotensin II. Thus, our work provides a novel insight into the underlying mechanism of the link

  12. 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.

  13. Traditional used Plants against Cognitive Decline and Alzheimer Disease

    PubMed Central

    Eckert, Gunter Peter

    2010-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory deficits, impaired cognitive function, and altered and inappropriate behavior. Aging represents the most important risk factor for AD and the global trend in the phenomenon of population aging has dramatic consequences for public health, healthcare financing, and delivery systems in the word and, especially in developing countries. Mounting evidence obtained in in vitro and in vivo studies, suggests that various traditionally used plants in Asia, India, and Europe significantly affect key metabolic alterations culminating in AD-typical neurodegeneration. The present article aims to bring the reader up-to-date on the most recent studies and advances describing the direct and indirect activities of traditional used plants and its constituents possibly relieving features of AD. A variety of traditional used plants and its extracts exerted activities on AD related drug targets including AChE activity, antioxidative activity, modulation of Aβ-producing secretase activities, Aβ-degradation, heavy metal chelating, induction of neurotrophic factors, and cell death mechanisms. Although pre-clinical investigations identified promising drug candidates for AD, clinical evidences are still pending. PMID:21833177

  14. Informant-Reported Cognitive Decline and Activity Engagement across Four Years in a Community Sample.

    PubMed

    Hosking, Diane E; Jiang, Da; Sargent-Cox, Kerry A; Anstey, Kaarin J

    2017-01-01

    Subtle age-related cognitive decline may be associated with the capacity to remain engaged in mental, physical, and social activities. Informant reports of cognitive decline potentially provide additional information to psychometric tests on change in everyday cognitive function relevant to activity engagement. To investigate relations between decline in everyday cognitive function as assessed by informant report and activity engagement in community-dwelling older adults. A sample of cognitively normal older adults was drawn from the 2 latest waves of the PATH Through Life Study (n = 1,391; mean age 74.5 ± 1.5, 48.4% female). PATH is a 16-year longitudinal cohort study set in the Canberra/Queanbeyan district, Australia. Assessments were carried out at baseline, and at 3 subsequent time-points 4 years apart. At wave-4, the IQCODE, an informant measure of 4-year cognitive decline was provided by a spouse, family member, or friend of each participant. Activity engagement was assessed by the abbreviated RIASEC Mental Activity List, self-reported frequency and duration of physical activity (Whitehall Questionnaire) and the Lubben Social Network Scale that assessed interaction with family/friends. Participants provided demographic information, self-reported health status (SF-12), and responses to the Goldberg Depression Scale. The Symbol Digit Modalities Test (SDMT) and California Verbal Learning Test (CVLT) were used to measure objective 4-year cognitive change. Those with MMSE score of ≤27 were excluded. IQCODE score predicted disengagement from mental activities over 4 years in cognitively healthy adults (β = -0.056, standard error [SE] = 0.019, p = 0.004). This association was robust to covariate control and change on the SDMT which was also significantly related to mental activity disengagement. In models adjusted for change scores on the SDMT and the CVLT, the IQCODE was associated with less physical (β = -0.692, SE = 0.24, p = 0.004) and social engagement (

  15. Prediction of Cognitive Decline in Healthy Older Adults using fMRI

    PubMed Central

    Woodard, John L.; Seidenberg, Michael; Nielson, Kristy A.; Smith, J. Carson; Antuono, Piero; Durgerian, Sally; Guidotti, Leslie; Zhang, Qi; Butts, Alissa; Hantke, Nathan; Lancaster, Melissa; Rao, Stephen M.

    2010-01-01

    Few studies have examined the extent to which structural and functional MRI, alone and in combination with genetic biomarkers, can predict future cognitive decline in asymptomatic elders. This prospective study evaluated individual and combined contributions of demographic information, genetic risk, hippocampal volume, and fMRI activation for predicting cognitive decline after an 18-month retest interval. Standardized neuropsychological testing, an fMRI scans semantic memory task (famous name discrimination), and structural MRI (sMRI) were performed on 78 healthy elders (73% female; mean age = 73 years, range = 65 to 88 years). Positive family history of dementia and presence of one or both apolipoprotein E (APOE) ε4 alleles occurred in 51.3% and 33.3% of the sample, respectively. Hippocampal volumes were traced from sMRI scans. At follow-up, all participants underwent a repeat neuropsychological examination. At 18 months, 27 participants (34.6%) declined by at least 1 SD on one of three neuropsychological measures. Using logistic regression, demographic variables (age, years of education, gender) and family history of dementia did not predict future cognitive decline. Greater fMRI activity, absence of an APOE ε4 allele, and larger hippocampal volume were associated with reduced likelihood of cognitive decline. The most effective combination of predictors involved fMRI brain activity and APOE ε4 status. Brain activity measured from task-activated fMRI, in combination with APOE ε4 status, was successful in identifying cognitively intact individuals at greatest risk for developing cognitive decline over a relatively brief time period. These results have implications for enriching prevention clinical trials designed to slow AD progression. PMID:20634590

  16. Accounting for bias due to selective attrition: The example of smoking and cognitive decline

    PubMed Central

    Weuve, Jennifer; Tchetgen Tchetgen, Eric J.; Glymour, M. Maria; Beck, Todd L.; Aggarwal, Neelum T.; Wilson, Robert S.; Evans, Denis A.; Mendes de Leon, Carlos F.

    2011-01-01

    Background Selective attrition may introduce bias into analyses of the determinants of cognitive decline. This is a concern especially for risk factors, such as smoking, that strongly influence mortality and drop-out. Using inverse-probability-of-attrition weights (IPAWs), we examined the influence of selective attrition on the estimated association of current smoking (versus never smoking) with cognitive decline. Methods Chicago Health and Aging Project participants (n=3,713), aged 65–109, who were current smokers or never-smokers underwent cognitive assessments up to 5 times at 3-year intervals. We used pooled logistic regression to fit predictive models of attrition due to death or study drop-out across the follow-up waves. With these models, we computed inverse-probability-of-attrition weights for each observation. We fit unweighted and weighted, multivariable-adjusted generalized-estimating-equation models, contrasting rates of change in cognitive scores in current versus never-smokers. Estimates are expressed as rates of change in z-score per decade. Results Over the 12 years of follow-up, smokers had higher mortality than never-smokers (hazard ratio= 1.93 [95% confidence interval= 1.67 to 2.23]). Higher previous cognitive score was associated with increased likelihood of survival and continued participation. In unweighted analyses, current smokers’ cognitive scores declined 0.11 standard units per decade more rapidly than never-smokers’ (95% CI= −0.20 to −0.02). Weighting to account for attrition yielded estimates that were 56%–86% larger, with smokers’ estimated 10-year rate of decline up to 0.20 units faster than never smokers’ (95% CI= −0.36 to −0.04). Conclusions Estimates of smoking’s effects on cognitive decline may be underestimated due to differential attrition. Analyses that weight for the inverse probability of attrition help - for this attrition. PMID:21989136

  17. Effect of Vitamin Intake on Cognitive Decline in Older Adults: Evaluation of the Evidence.

    PubMed

    Krause, D; Roupas, P

    2015-08-01

    The objective of this review was to evaluate the evidence from human studies on the intake of vitamins, either as monotherapies or in combination with other vitamins, as neuroprotective agents that may delay the onset of cognitive decline in older adults. Evidence-based methodologies were used to capture and evaluate the highest levels of evidence. The current evidence available showed no association for cognitive benefits of vitamins B6 or B12 as a monotherapy, and recent systematic reviews provide no clear evidence that supplementation with vitamin B6, B12 and/or folic acid improves dementia outcomes or slows cognitive decline, even though it may normalise homocysteine levels. Meta-analyses from systematic reviews have shown an association between low vitamin D levels and diminished cognitive function, although causality cannot be confirmed from the available evidence. There is no convincing evidence for an association of vitamin A, vitamin C or vitamin E either as a monotherapy or in combination with other antioxidant vitamins such as β-carotene and the prevention of cognitive decline. The appraisal of nineteen systematic reviews and meta-analyses has highlighted the heterogeneity between studies, and the need for better consensus on definitions of cognitive decline, duration of testing and agreement on which specific endpoints are clinically relevant. Evaluation of the totality of the currently available evidence indicates that intake of the above vitamins, either as a monotherapy, or in combination with other vitamins, has no clinically-relevant effect on delaying cognitive decline or delaying the onset of dementia in older adults.

  18. Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly

    PubMed Central

    Lesnick, Timothy G.; Przybelski, Scott A.; Knopman, David S.; Preboske, Greg M.; Kantarci, Kejal; Raman, Mekala R.; Machulda, Mary M.; Mielke, Michelle M.; Lowe, Val J.; Senjem, Matthew L.; Gunter, Jeffrey L.; Rocca, Walter A.; Roberts, Rosebud O.; Petersen, Ronald C.; Jack, Clifford R.

    2015-01-01

    Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with

  19. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline.

    PubMed

    Raji, C A; Eyre, H; Wei, S H; Bredesen, D E; Moylan, S; Law, M; Small, G; Thompson, P M; Friedlander, R M; Silverman, D H; Baune, B T; Hoang, T A; Salamon, N; Toga, A W; Vernooij, M W

    2015-10-01

    Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity.

  20. Critical levels of brain atrophy associated with homocysteine and cognitive decline.

    PubMed

    de Jager, Celeste A

    2014-09-01

    Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Caffeine intake is associated with a lower risk of cognitive decline: a cohort study from Portugal.

    PubMed

    Santos, Catarina; Lunet, Nuno; Azevedo, Ana; de Mendonça, Alexandre; Ritchie, Karen; Barros, Henrique

    2010-01-01

    Alzheimer's disease has emerged in recent decades as a major health problem and the role of lifestyles in the modulation of risk has been increasingly recognized. Recent epidemiological studies suggest a protective effect for caffeine intake in dementia. We aimed to quantify the association between caffeine dietary intake and cognitive decline, in a cohort of adults living in Porto. A cohort of 648 subjects aged > or =65 years was recruited between 1999-2003. Follow-up evaluation (2005-2008) was carried out on 58.2% of the eligible participants and 10.9% were deceased. Caffeine exposure in the year preceding baseline evaluation was assessed with a validated food frequency questionnaire. Cognitive evaluation consisted of baseline and follow-up Mini-Mental State Examination (MMSE). Cognitive decline was defined by a decrease > or =2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95%CI) estimates adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes were computed using Poisson regression. Caffeine intake (> 62 mg/day [3rd third] vs. < 22 mg/day [1st third]) was associated with a lower risk of cognitive decline in women (RR=0.49, 95%CI 0.24-0.97), but not significantly in men (RR=0.65, 95%CI 0.27-1.54). Our study confirms the negative association between caffeine and cognitive decline in women.

  2. 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

  3. Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease.

    PubMed

    Bäckström, D; Eriksson Domellöf, M; Granåsen, G; Linder, J; Mayans, S; Elgh, E; Zetterberg, H; Blennow, K; Forsgren, L

    2017-09-04

    Cognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2-receptor availability (Catechol-O-methyltransferase [COMT] Val(158) Met genotype and DRD2 C(957) T genotype) affect the development of cognitive deficits in PD. One hundred and 34 patients with idiopathic PD, participating in a regional, population-based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6-10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD-MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome. Both genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT (158) Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P = .023), the DRD2 (957) T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P < .001). The poorer cognitive performance in DRD2 (957) T/T carriers with PD occurred mainly in episodic memory and attention. The results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas. © 2017 The Authors. Acta Neurologica Scandinavica Published by John Wiley & Sons Ltd.

  4. Does Intensive Glucose Control Prevent Cognitive Decline in Diabetes? A Meta-Analysis

    PubMed Central

    Peñaherrera-Oviedo, Carlos; Moreno-Zambrano, Daniel; Palacios, Michael; Duarte-Martinez, María Carolina; Cevallos, Carlos; Gamboa, Ximena; Jurado, María Beatriz; Tamariz, Leonardo; Palacio, Ana; Santibañez, Rocío

    2015-01-01

    Diabetes mellitus is associated with cognitive decline and impaired performance in cognitive function tests among type 1 and type 2 diabetics. Even though the use of tight glucose control has been limited by a reported higher mortality, few reports have assessed the impact of treatment intensity on cognitive function. We conducted a meta-analysis to evaluate if an intensive glucose control in diabetes improves cognitive function, in comparison to standard therapy. We included 7 studies that included type 1 or type 2 diabetics and used standardized tests to evaluate various cognitive function domains. Standardized mean differences (SMDs) were calculated for each domain. We found that type 1 diabetics get no cognitive benefit from a tight glucose control, whereas type 2 diabetics get some benefit on processing speed and executive domains but had worse performances in the memory and attention domains, along with a higher incidence of mortality when using intensive glucose control regimes. PMID:26464871

  5. Long-term digital mobile phone use and cognitive decline in the elderly.

    PubMed

    Ng, Tze Pin; Lim, May Li; Niti, Mathew; Collinson, Simon

    2012-02-01

    Research on long-term exposure to electromagnetic fields on cognition is lacking. We investigated the associations between frequent digital mobile phone use and global and domain-specific cognitive changes in older persons, a vulnerable group experiencing age-associated cognitive decline. We assessed 871 non-demented Chinese participants in the Singapore Longitudinal Ageing Studies cohort on the frequency of digital mobile phone use, neurocognitive performance and confounding variables at baseline, and neurocognitive performance at the 4-year follow-up. Findings showed that digital mobile phone users were typically self-selected to possess characteristics favoring better cognitive functioning and concomitantly demonstrate better performance on cognitive tasks. There was evidently no significant deleterious effect of digital mobile phone use on cognitive functioning in older people. Findings suggest, however, that digital mobile phone use may have an independent facilitating effect on global and executive functioning. Copyright © 2011 Wiley Periodicals, Inc.

  6. 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.

  7. Fetuin-A, a New Vascular Biomarker of Cognitive Decline in Older Adults

    PubMed Central

    Laughlin, Gail A; McEvoy, Linda K.; Barrett-Connor, Elizabeth; Daniels, Lori B.; Ix, Joachim H.

    2014-01-01

    Objectives Fetuin-A is an abundant plasma protein known to predict vascular disease. Fetuin-A levels are lower in patients with Alzheimer’s disease in proportion to the severity of cognitive impairment, but their association with normal cognitive aging is unknown. We evaluated the association of serum fetuin-A levels with cognitive function in community-dwelling older adults. Design/Patients/Measurements A population-based study of 1382 older adults (median age 75) who had plasma fetuin-A levels and cognitive function evaluated in 1992–96; 855 had repeat cognitive function assessment a median of 4 years later. Results Adjusting for age, sex, education, and depression, higher levels of fetuin-A were associated with better baseline performance on the Mini-Mental Status Exam (MMSE) (P=0.012) and a tendency for better Trails Making B scores (P=0.066). In longitudinal analyses, the likelihood of a major decline (highest decile of change) in Trails B was 29% lower (P=0.010) for each SD higher baseline fetuin-A level; odds of major decline in MMSE was 42% lower (P=0.005) per SD higher fetuin-A for individuals with no known CVD, but were not related to fetuin-A in those with CVD (P=0.33). Fetuin-A was not related to Category Fluency performance. Results were independent of multiple vascular risk factors and comorbid conditions. Conclusions Higher plasma fetuin-A concentrations are associated with better performance on tests of global cognitive function and executive function and with less likelihood of major decline in these cognitive abilities over a 4-year period. Fetuin-A may serve as a biological link between vascular disease and normal age-related cognitive decline. PMID:24325554

  8. Fetuin-A, a new vascular biomarker of cognitive decline in older adults.

    PubMed

    Laughlin, Gail A; McEvoy, Linda K; Barrett-Connor, Elizabeth; Daniels, Lori B; Ix, Joachim H

    2014-07-01

    Fetuin-A is an abundant plasma protein known to predict vascular disease. Fetuin-A levels are lower in patients with Alzheimer's disease in proportion to the severity of cognitive impairment, but their association with normal cognitive ageing is unknown. We evaluated the association of serum fetuin-A levels with cognitive function in community-dwelling older adults. A population-based study of 1382 older adults (median age 75) who had plasma fetuin-A levels and cognitive function evaluated in 1992-1996; 855 had repeat cognitive function assessment a median of 4 years later. Adjusting for age, sex, education and depression, higher levels of fetuin-A were associated with better baseline performance on the Mini-Mental Status Exam (MMSE; P = 0·012) and a tendency for better Trails Making B scores (P = 0·066). In longitudinal analyses, the likelihood of a major decline (highest decile of change) in Trails B was 29% lower (P = 0·010) for each SD higher baseline fetuin-A level; odds of major decline in MMSE was 42% lower (P = 0·005) per SD higher fetuin-A for individuals with no known CVD, but were not related to fetuin-A in those with CVD (P = 0·33). Fetuin-A was not related to Category Fluency performance. Results were independent of multiple vascular risk factors and comorbid conditions. Higher plasma fetuin-A concentrations are associated with better performance on tests of global cognitive function and executive function and with less likelihood of major decline in these cognitive abilities over a 4-year period. Fetuin-A may serve as a biological link between vascular disease and normal age-related cognitive decline. © 2013 John Wiley & Sons Ltd.

  9. Subtle Cognitive Decline and Biomarker Staging in Preclinical Alzheimer’s Disease

    PubMed Central

    Edmonds, Emily C.; Delano-Wood, Lisa; Galasko, Douglas R.; Salmon, David P.; Bondi, Mark W.

    2015-01-01

    The NIA-AA criteria for “preclinical” Alzheimer’s disease (AD) propose a staging method in which AD biomarkers follow an invariable temporal sequence in accordance with the amyloid cascade hypothesis. However, recent findings do not align with the proposed temporal sequence and “subtle cognitive decline,” which has not been definitively operationalized, may occur earlier than suggested in preclinical AD. We aimed to define “subtle cognitive decline” using sensitive and reliable neuropsychological tests, and to examine the number and sequence of biomarker abnormalities in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). 570 cognitively normal ADNI participants were classified based on NIA-AA criteria and separately based on the number of abnormal biomarkers/cognitive markers associated with preclinical AD that each individual possessed. Results revealed that neurodegeneration alone was 2.5 times more common than amyloidosis alone at baseline. For those who demonstrated only one abnormal biomarker at baseline and later progressed to mild cognitive impairment/AD, neurodegeneration alone was most common, followed by amyloidosis alone or subtle cognitive decline alone, which were equally common. Findings suggest that most individuals do not follow the temporal order proposed by NIA-AA criteria. We provide an operational definition of subtle cognitive decline that captures both cognitive and functional decline. Additionally, we offer a new approach for staging preclinical AD based on number of abnormal biomarkers, without regard to their temporal order of occurrence. This method of characterizing preclinical AD is more parsimonious than the NIA-AA staging system and does not presume that all patients follow a singular invariant expression of the disease. PMID:26402771

  10. Subjective Cognitive Complaints Relate to White Matter Hyperintensities and Future Cognitive Decline in Patients with Cardiovascular Disease

    PubMed Central

    Haley, Andreana P.; Hoth, Karin F.; Gunstad, John; Paul, Robert H.; Jefferson, Angela L.; Tate, David F.; Ono, Makoto; Jerskey, Beth A.; Poppas, Athena; Sweet, Lawrence H.; Cohen, Ronald A.

    2009-01-01

    Objective Elderly patients with cardiovascular disease (CVD) often report cognitive difficulties including reduced cognitive processing speed and attention. On cross-sectional examination, such reports relate more closely to mood than to objective measures of cognitive performance, thus questioning the validity of subjective cognitive complaints as a marker of neurodegenerative processes. This study examined the longitudinal relationship between self-reported cognitive difficulties, depression, and performance on objective tests of global cognition in patients with CVD. Participants and Methods Forty-seven CVD patients (ages 55 to 85 years) completed a measure of perceived cognitive dysfunction (Cognitive Difficulties Scale), a medical history questionnaire, the Dementia Rating Scale (DRS), and the Beck Depression Inventory (BDI) at baseline and 12 months later. Baseline brain imaging was available on a small sub-sample (n = 17). Results Hierarchical linear regression revealed that increased report of cognitive difficulties at baseline was significantly associated with poorer DRS performance at follow-up (F(3, 43) = 4.45, p = .008, CDS partial r = −.30, p = .048), independent of age, education, baseline DRS and BDI scores. Greater perceived cognitive dysfunction at baseline also related to higher level of white matter lesions (r = .53, df = 15, p = .028). Conclusions Self-reported cognitive difficulties may reflect early changes in cognitive aging that are difficult to detect using global cognitive screening measures at a single time point. Yet, these perceived difficulties relate to objectively measured cognitive decline over time. Thus, they may provide important clinical information about early neurodegenerative processes that should be carefully monitored. PMID:20104055

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

    PubMed

    Forlini, Cynthia; Hall, Wayne

    2017-10-04

    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.

  12. Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline.

    PubMed

    Peiffer, Ann M; Leyrer, C Marc; Greene-Schloesser, Dana M; Shing, Elaine; Kearns, William T; Hinson, William H; Tatter, Stephen B; Ip, Edward H; Rapp, Stephen R; Robbins, Mike E; Shaw, Edward G; Chan, Michael D

    2013-02-19

    In a retrospective review to assess neuroanatomical targets of radiation-induced cognitive decline, dose volume histogram (DVH) analyses of specific brain regions of interest (ROI) are correlated to neurocognitive performance in 57 primary brain tumor survivors. Neurocognitive assessment at baseline included Trail Making Tests A/B, a modified Rey-Osterreith Complex Figure, California or Hopkins Verbal Learning Test, Digit Span, and Controlled Oral Word Association. DVH analysis was performed for multiple neuroanatomical targets considered to be involved in cognition. The %v10 (percent of ROI receiving 10 Gy), %v40, and %v60 were calculated for each ROI. Factor analysis was used to estimate global cognition based on a summary of performance on individual cognitive tests. Stepwise regression was used to determine which dose volume predicted performance on global factors and individual neurocognitive tests for each ROI. Regions that predicted global cognitive outcomes at doses <60 Gy included the corpus callosum, left frontal white matter, right temporal lobe, bilateral hippocampi, subventricular zone, and cerebellum. Regions of adult neurogenesis primarily predicted cognition at %v40 except for the right hippocampus which predicted at %v10. Regions that did not predict global cognitive outcomes at any dose include total brain volume, frontal pole, anterior cingulate, right frontal white matter, and the right precentral gyrus. Modeling of radiation-induced cognitive decline using neuroanatomical target theory appears to be feasible. A prospective trial is necessary to validate these data.

  13. Sub-Clinical Cognitive Decline and Resting Cerebral Blood Flow in Middle Aged Men

    PubMed Central

    Henriksen, Otto Mølby; Hansen, Naja Liv; Osler, Merete; Mortensen, Erik Lykke; Hallam, Dorte Merete; Pedersen, Esben Thade; Chappell, Michael; Lauritzen, Martin Johannes; Rostrup, Egill

    2017-01-01

    Background Although dementia is associated with both global and regional cerebral blood flow (CBF) changes, little is known about cerebral perfusion in the early pre-clinical stages of cognitive decline preceding overt cognitive dysfunction. The aim of this study was to investigate the association of early sub-clinical cognitive decline with CBF. Materials and Methods The study participants were recruited from a cohort of Danish men born in 1953. Based on a regression model we selected men who performed better (Group A, n = 94) and poorer (Group B, n = 95) on cognitive testing at age 57 than expected from testing at age 20. Participants underwent supplementary cognitive testing, blood sampling and MRI including measurements of regional and global CBF. Results Regional CBF was lower in group B than in group A in the posterior cingulate gyrus and the precuneus. The associations were attenuated when corrected for global atrophy, but remained significant in regions of interest based analysis adjusting for regional gray matter volume and vascular risk factors. No influence of group on global CBF was observed. Conclusions We conclude that early sub-clinical cognitive decline is associated with reduced perfusion in the precuneus and posterior cingulate gyrus independently of regional atrophy and vascular risk factors, but cannot be statistically separated from an association with global atrophy. PMID:28095458

  14. Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

    PubMed Central

    Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K.

    2016-01-01

    Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets. PMID:27114845

  15. 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

  16. Development and validation of risk index for cognitive decline using blood-derived markers

    PubMed Central

    Ayonayon, Hilsa; Harris, Tamara; Phillips, Caroline; Rosano, Caterina; Satterfield, Suzanne; Yaffe, Kristine

    2015-01-01

    Objective: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. Methods: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. Results: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: −0.46, −0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: −0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: −0.85, −0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: −0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: −0.72, −0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: −1.14, −0.51). Conclusions: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary. PMID:25609760

  17. Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

    PubMed

    Lehrner, J; Coutinho, G; Mattos, P; Moser, D; Pflüger, M; Gleiss, A; Auff, E; Dal-Bianco, P; Pusswald, G; Stögmann, E

    2017-07-01

    Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

  18. B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study.

    PubMed

    Hughes, Catherine F; Ward, Mary; Tracey, Fergal; Hoey, Leane; Molloy, Anne M; Pentieva, Kristina; McNulty, Helene

    2017-01-10

    Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60-88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9-1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28-13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing.

  19. B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study

    PubMed Central

    Hughes, Catherine F.; Ward, Mary; Tracey, Fergal; Hoey, Leane; Molloy, Anne M.; Pentieva, Kristina; McNulty, Helene

    2017-01-01

    Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing. PMID:28075382

  20. Subjective Cognitive Decline Modifies the Relationship Between Cerebral Blood Flow and Memory Function in Cognitively Normal Older Adults.

    PubMed

    Hays, Chelsea C; Zlatar, Zvinka Z; Campbell, Laura; Meloy, M J; Wierenga, Christina E

    2017-10-04

    Subjective cognitive decline (SCD), or self-reported cognitive decline despite normal neuropsychological test performance, is a risk factor for objective cognitive decline and Alzheimer's disease (AD). While brain mechanisms contributing to SCD are not well defined, studies show associations with vascular risk factors and altered cerebral blood flow (CBF), raising the hypothesis that those with SCD might be experiencing vascular dysregulation, or a disruption in the normal relationship between CBF and cognition. We examined whether the association between CBF and verbal memory performance differs between those with SCD (SCD+) and those without SCD (SCD-). Linear mixed-effects models were used to investigate whether the voxel-wise relationship between arterial spin labeling (ASL) MRI-measured CBF and verbal memory performance was modified by SCD among a group of 70 cognitively normal older adults (35 SCD+, 35 SCD-; mean age=72) matched on age, gender, and symptoms of depression. Results indicated that the SCD- group exhibited positive associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, and inferior frontal gyrus, whereas the SCD+ group displayed negative associations between verbal memory and CBF within the posterior cingulate cortex, middle temporal gyrus, hippocampus, fusiform gyrus, and inferior frontal gyrus. Findings suggest that, while higher CBF is supportive of memory function in those without SCD, higher CBF may no longer support memory function in those presenting with SCD, perhaps reflecting neurovascular dysregulation. (JINS, 2017, 23, 1-11).

  1. Renal function and long-term decline in cognitive function: the Baltimore Longitudinal Study of Aging.

    PubMed

    Seliger, Stephen L; Wendell, Carrington R; Waldstein, Shari R; Ferrucci, Luigi; Zonderman, Alan B

    2015-01-01

    Renal disease has been associated with greater risk of dementia and greater cognitive impairment. However, the relationship of lower renal function with long-term decline in specific domains of cognitive function remains unclear among community-dwelling, non-demented individuals. Stroke- and dementia-free participants (n = 2,116) were enrolled in the Baltimore Longitudinal Study of Aging, a community-based, prospective, longitudinal study. Renal function was estimated by the inverse of serum creatinine adjusted for age, sex and race and (in sensitivity analyses) estimated glomerular filtration rate (eGFR) using the MDRD formula. Outcome measures were changes in scores on 6 cognitive tests encompassing a range of cognitive functions, measured at 2-year intervals. Mixed-effects regression models examined the longitudinal relations of renal function with cognitive functions after adjusting for demographics, comorbidity and other potential confounders. Mean age at initial testing was 53.9 years (SD 17.1), and 94 participants (4.4%) had an eGFR <60 ml/min/1.73 m(2) and 18.5% had at least one comorbidity. With increasing age, longitudinal increases in creatinine concentrations were associated with more rapid decline in performance on several cognitive measures, including the learning slope of the California Verbal Learning Test, a test of verbal learning (p < 0.01), and the Benton Visual Retention Test, a test of visual memory (p < 0.01). Associations were similar for changes in eGFRMDRD, which was also associated with the rate of decline in verbal memory. In a community-based adult population, declines in renal function independently associated with greater long-term declines in visual memory and verbal memory and learning. © 2015 National Institutes of Health (NIH). Published by S. Karger AG, Basel.

  2. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population.

    PubMed

    Tangney, Christine C; Kwasny, Mary J; Li, Hong; Wilson, Robert S; Evans, Denis A; Morris, Martha Clare

    2011-03-01

    Many of the foods abundant in the traditional Mediterranean diet, such as vegetables and fish, have been associated with slower cognitive decline. We investigated whether adherence to a Mediterranean dietary pattern or to the Healthy Eating Index-2005 (HEI-2005) is associated with cognitive change in older adults. This article is based on analyses of data from an ongoing longitudinal study in adults aged ≥65 y known as the Chicago Health and Aging Project (CHAP). CHAP participants (2280 blacks and 1510 whites) with ≥2 cognitive assessments were evaluated for adherence to 1) the Mediterranean dietary pattern (MedDiet; maximum score: 55) and 2) the HEI-2005 (maximum score: 100). For both scoring systems, higher scores connote greater adherence. Cognitive function was assessed at 3-y intervals on the basis of a composite measure of global cognition. Linear mixed models were used to examine the association of dietary scores to change in cognitive function. Mean follow-up time was 7.6 y. Mean (±SD) scores for participants were 28.2 ± 0.1 for the MedDiet and 61.2 ± 9.6 for the HEI-2005. White participants had higher energy-adjusted MedDiet scores but lower HEI-2005 scores than did black participants. Higher MedDiet scores were associated with slower rates of cognitive decline (β = +0.0014 per 1-point increase, SEE = 0.0004, P = 0.0004) after adjustment for age, sex, race, education, participation in cognitive activities, and energy. No such associations were observed for HEI-2005 scores. The Mediterranean dietary pattern as captured by the MedDiet scoring system may reduce the rate of cognitive decline with older age.

  3. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population123

    PubMed Central

    Tangney, Christine C; Kwasny, Mary J; Li, Hong; Wilson, Robert S; Evans, Denis A; Morris, Martha Clare

    2011-01-01

    Background: Many of the foods abundant in the traditional Mediterranean diet, such as vegetables and fish, have been associated with slower cognitive decline. Objective: We investigated whether adherence to a Mediterranean dietary pattern or to the Healthy Eating Index–2005 (HEI-2005) is associated with cognitive change in older adults. Design: This article is based on analyses of data from an ongoing longitudinal study in adults aged ≥65 y known as the Chicago Health and Aging Project (CHAP). CHAP participants (2280 blacks and 1510 whites) with ≥2 cognitive assessments were evaluated for adherence to 1) the Mediterranean dietary pattern (MedDiet; maximum score: 55) and 2) the HEI-2005 (maximum score: 100). For both scoring systems, higher scores connote greater adherence. Cognitive function was assessed at 3-y intervals on the basis of a composite measure of global cognition. Linear mixed models were used to examine the association of dietary scores to change in cognitive function. Mean follow-up time was 7.6 y. Results: Mean (±SD) scores for participants were 28.2 ± 0.1 for the MedDiet and 61.2 ± 9.6 for the HEI-2005. White participants had higher energy-adjusted MedDiet scores but lower HEI-2005 scores than did black participants. Higher MedDiet scores were associated with slower rates of cognitive decline (β = +0.0014 per 1-point increase, SEE = 0.0004, P = 0.0004) after adjustment for age, sex, race, education, participation in cognitive activities, and energy. No such associations were observed for HEI-2005 scores. Conclusion: The Mediterranean dietary pattern as captured by the MedDiet scoring system may reduce the rate of cognitive decline with older age. PMID:21177796

  4. Role of physical activity in reducing cognitive decline in older Mexican-American adults.

    PubMed

    Ottenbacher, Allison J; Snih, Soham Al; Bindawas, Saad M; Markides, Kyriakos S; Graham, James E; Samper-Ternent, Rafael; Raji, Mukaila; Ottenbacher, Kenneth J

    2014-09-01

    The effect of physical activity on cognitive function in older adults from minority and disadvantaged populations is not well understood. This study examined the longitudinal association between physical activity and cognition in older Mexican Americans. The study methodology included a prospective cohort with longitudinal analysis of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly. General linear mixed models were used to assess the associations and interactions between physical activity and cognitive function over 14 years. Community-based assessments were performed in participants' homes. Physical activity was recorded for 1,669 older Mexican Americans using the Physical Activity Scale for the Elderly. Cognition was measured using the Mini-Mental State Examination (MMSE) and separated into memory and nonmemory components. A statistically significant positive association was observed between levels of physical activity and cognitive function after adjusting for age, sex, marital status, education, and comorbid health conditions. There was a statistically significant difference in MMSE scores over time between participants in the third (β = 0.11, standard error (SE) = 0.05) and fourth (β = 0.10, SE = 0.2) quartiles of physical activity and those in the first. The protective effect of physical activity on cognitive decline was evident for the memory component of the MMSE but not the nonmemory component after adjusting for covariates. Greater physical activity at baseline was associated with less cognitive decline over 14 years in older Mexican Americans. The reduction in cognitive decline appeared to be related to the memory components of cognitive function.

  5. APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease

    PubMed Central

    Lim, Y Y; Villemagne, V L; Laws, S M; Pietrzak, R H; Snyder, P J; Ames, D; Ellis, K A; Harrington, K; Rembach, A; Martins, R N; Rowe, C C; Masters, C L; Maruff, P

    2015-01-01

    Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4+], ɛ4 non-carrier[ɛ4−]) and brain-derived neurotrophic factor (BDNFVal/Val, BDNFMet) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ− or Aβ+. Relative to Aβ−ɛ4−, Aβ+ɛ4+ individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40–1.22), while Aβ+ɛ4− individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ−ɛ4− and Aβ−ɛ4+ groups. Among Aβ+ individuals, ɛ4+/BDNFMet participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4−/BDNFVal/Val participants (d=0.90–1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ+ɛ4+/BDNFMet individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ+ɛ4+/BDNFVal/Val individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ− and Aβ+ ɛ4− groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials. PMID:25288138

  6. Drinking Hydrogen Water Ameliorated Cognitive Impairment in Senescence-Accelerated Mice

    PubMed Central

    Gu, Yeunhwa; Huang, Chien-Sheng; Inoue, Tota; Yamashita, Takenori; Ishida, Torao; Kang, Ki-Mun; Nakao, Atsunori

    2010-01-01

    Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders. PMID:20490324

  7. Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice.

    PubMed

    Gu, Yeunhwa; Huang, Chien-Sheng; Inoue, Tota; Yamashita, Takenori; Ishida, Torao; Kang, Ki-Mun; Nakao, Atsunori

    2010-05-01

    Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.

  8. Crowdsourced estimation of cognitive decline and resilience in Alzheimer’s disease

    PubMed Central

    Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Neto, Elias Chaibub; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard JB; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Jiang, Qijia; Katsumata, Yuriko; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Lyappan, Anandhi; Ma, Michelle; Malhotra, Ashutosh; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

    2017-01-01

    Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer’s Disease. The Alzheimer’s Disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer’s Disease based on high-dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for to prediction of cognitive performance. PMID:27079753

  9. CR1 is associated with amyloid plaque burden and age-related cognitive decline

    PubMed Central

    Chibnik, Lori B.; Shulman, Joshua M.; Leurgans, Sue E.; Schneider, Julie A.; Wilson, Robert S.; Tran, Dong; Aubin, Cristin; Buchman, Aron S.; Heward, Christopher B.; Myers, Amanda J.; Hardy, John A.; Huentelman, Matthew J.; Corneveaux, Jason J.; Reiman, Eric M.; Evans, Denis A.; Bennett, David A.; De Jager, Philip L.

    2010-01-01

    OBJECTIVE Recently, genome-wide association studies have identified three new susceptibility loci for Alzheimer’s disease (AD), CLU, CR1, and PICALM. We leveraged available neuropsychological and autopsy data from two cohort studies to investigate whether these loci are associated with cognitive decline and AD neuropathology. METHODS The Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP) are longitudinal studies that enroll non-demented subjects and include annual clinical evaluations and brain donation at death. We evaluated CR1 (rs6656401), CLU (rs11136000) and PICALM (rs7110631) in 1666 subjects. We evaluated associations between genotypes and rate of change in cognitive function as well as AD-related pathology. Lastly, we used pathway analysis to determine if relationships between SNPs and cognitive decline were mediated through AD pathology. RESULTS Among our study cohort, the mean years of follow-up was 7.8 for ROS and 4.3 for MAP. Only the CR1 locus was associated with both global cognitive decline (p=0.011) and global AD pathology (p=0.025). More specifically, the locus affects the deposition of neuritic amyloid plaque (p=0.009). In a mediation analysis, controlling for amyloid pathology strongly attenuated the effect of the CR1 locus on cognitive decline. INTERPRETATION We found that common variation at the CR1 locus has a broad impact on cognition and that this effect is largely mediated by an individual’s amyloid plaque burden. We therefore highlight one functional consequence of the CR1 susceptibility allele and generalize the role of this locus to cognitive aging in the general population. PMID:21391232

  10. Recent Advances in Berry Supplementation and Age-Related Cognitive Decline

    USDA-ARS?s Scientific Manuscript database

    To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...

  11. Chemotheraphy, Neurotoxicity, and Cognitive Decline: Developing a Mouse Model and Potential Interventions

    DTIC Science & Technology

    2011-09-01

    weight- loss but no significant animal loss , during the experiment proper our dosing caused systematic animal death which resulted in the chemotherapy ...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Adjuvant chemotherapy often causes cognitive decline in breast...can have a deleterious impact on survivor quality of life. Recent evidence shows that chemotherapy agents can have long-lasting neurotoxic effects

  12. Beneficial Effects of Yogasanas and Pranayama in limiting the Cognitive decline in Type 2 Diabetes

    PubMed Central

    Rajani, Santhakumari; Archana, Rajagopalan; Indla, Yogananda Reddy; Rajesh, P

    2016-01-01

    Background Out of many complications that were observed in type 2 diabetes, cognitive impairment is the most neglected. Aim and Objectives The aim of the present study is to assess the cognitive decline in type 2 diabetes and to observe the role of yogasanas and pranayama in ameliorating the cognitive decline. Materials and methods Sixty eight type 2 diabetic subjects were recruited in the study, 34 of them did specific yogasanas and pranayama (test group) for six months and the remaining age and sex matched 34 subjects were recruited as (control group) who were not on any specific exercise regimen. Glycaemic index was estimated by measuring the glycosylated haemoglobin (HbA1c) concentration with Bio-Rad apparatus and cognition was assessed by using Addenbrook’s Cognitive Examination-Revised (ACE-R), which is a neuropsychological battery. Statistical analysis Data was analysed with unpaired student t test. P value<0.05 is considered as statistically significant. Validity was assessed by receiver operating characteristics Results Analysis of data indicated more cognitive scores in the test group when compared with the control group. In test group six months practice of yogasanas and pranayama has also significantly brought down the high glycaemic values which were observed in the control group. Conclusion These findings allow the study to conclude that regular practice of yogasanas and pranayama has a beneficial effect on cognitive performance in type 2 diabetic subjects by stabilizing blood glucose.

  13. Beneficial Effects of Yogasanas and Pranayama in limiting the Cognitive decline in Type 2 Diabetes.

    PubMed

    Rajani, Santhakumari; Archana, Rajagopalan; Indla, Yogananda Reddy; Rajesh, P

    2017-01-01

    Out of many complications that were observed in type 2 diabetes, cognitive impairment is the most neglected. The aim of the present study is to assess the cognitive decline in type 2 diabetes and to observe the role of yogasanas and pranayama in ameliorating the cognitive decline. Sixty eight type 2 diabetic subjects were recruited in the study, 34 of them did specific yogasanas and pranayama (test group) for six months and the remaining age and sex matched 34 subjects were recruited as (control group) who were not on any specific exercise regimen. Glycaemic index was estimated by measuring the glycosylated haemoglobin (HbA1c) concentration with Bio-Rad apparatus and cognition was assessed by using Addenbrook's Cognitive Examination-Revised (ACE-R), which is a neuropsychological battery. Data was analysed with unpaired student t test. P value<0.05 is considered as statistically significant. Validity was assessed by receiver operating characteristics. Analysis of data indicated more cognitive scores in the test group when compared with the control group. In test group six months practice of yogasanas and pranayama has also significantly brought down the high glycaemic values which were observed in the control group. These findings allow the study to conclude that regular practice of yogasanas and pranayama has a beneficial effect on cognitive performance in type 2 diabetic subjects by stabilizing blood glucose.

  14. Nutritional Deficiency in Early Life Facilitates Aging-Associated Cognitive Decline.

    PubMed

    Kang, Yu; Zhang, Yun; Feng, Zijuan; Liu, Mingjing; Li, Yanhua; Yang, Huan; Wang, Dan; Zheng, Lingling; Lou, Dandan; Cheng, Liangping; Chen, Chunjiang; Zhou, Weitao; Feng, Yi; Li, Xiaoyong; Duan, Jianzhong; Yu, Mengjiao; Yang, Shou; Liu, Yuhang; Wang, Xin; Deng, Bo; Liu, Chenghui; Yao, Xiuqing; Zhu, Chi; Liang, Chunrong; Zeng, Xiaolong; Ren, Sisi; Li, Qunying; Zhong, Yin; Zhang, Yong; Kang, Jun; Yan, Yong; Meng, Huaqing; Zhong, Zhaohui; Zhou, Weihui; Wang, Yanjiang; Li, Tingyu; Song, Weihong

    2017-01-01

    Nutrition is important for the fetal developmental programming. Nutritional deficiency in early life could increase the susceptibility to many aging-related disorders including cognitive decline. Our study aims to investigate the effect of early famine exposure on aging-associated cognitive function. We recruited 6790 subjects born between 1956 to 1964 during which the Great Chinese Famine occurred (1959-1961). Cognitive function of these subjects were evaluated using the Mini-Mental State Examination (MMSE), the Activities of Daily Living scale (ADL), the Instrumental Activities of Daily Living scale (IADL) and the Clinical Dementia Rating (CDR). Our study identified that early exposure to the famine significantly increased the risk of cognitive impairments in later life, leading to higher prevalence of Mild Cognitive Impairment (MCI) and dementia. We also found the sex and rural-urban differences in this malnutrition-induced effect. Illiteracy, history of stroke or diabetes mellitus are great risk factors to facilitate the cognitive decline. These findings demonstrate that exposure to famine during early life including prenatal period and early childhood facilitates aging-associated cognitive deficits. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Prayer at midlife is associated with reduced risk of cognitive decline in Arabic women.

    PubMed

    Inzelberg, Rivka; Afgin, Anne E; Massarwa, Magda; Schechtman, Edna; Israeli-Korn, Simon D; Strugatsky, Rosa; Abuful, Amin; Kravitz, Efrat; Farrer, Lindsay A; Friedland, Robert P

    2013-03-01

    Midlife habits may be important for the later development of Alzheimer's disease (AD). We estimated the contribution of midlife prayer to the development of cognitive decline. In a door-to-door survey, residents aged ≥65 years were systematically evaluated in Arabic including medical history, neurological, cognitive examination, and a midlife leisure-activities questionnaire. Praying was assessed by the number of monthly praying hours at midlife. Stepwise logistic regression models were used to evaluate the effect of prayer on the odds of mild cognitive impairment (MCI) and AD versus cognitively normal individuals. Of 935 individuals that were approached, 778 [normal controls (n=448), AD (n=92) and MCI (n=238)] were evaluated. A higher proportion of cognitively normal individuals engaged in prayer at midlife [(87%) versus MCI (71%) or AD (69%) (p<0.0001)]. Since 94% of males engaged in prayer, the effect on cognitive decline could not be assessed in men. Among women, stepwise logistic regression adjusted for age and education, showed that prayer was significantly associated with reduced risk of MCI (p=0.027, OR=0.55, 95% CI 0.33-0.94), but not AD. Among individuals endorsing prayer activity, the amount of prayer was not associated with MCI or AD in either gender. Praying at midlife is associated with lower risk of mild cognitive impairment in women.

  16. Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline

    ERIC Educational Resources Information Center

    Pakhomov, Serguei V. S.; Hemmy, Laura S.; Lim, Kelvin O.

    2012-01-01

    The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer's disease and mild cognitive impairment are…

  17. Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline

    ERIC Educational Resources Information Center

    Pakhomov, Serguei V. S.; Hemmy, Laura S.; Lim, Kelvin O.

    2012-01-01

    The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer's disease and mild cognitive impairment are…

  18. Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia

    PubMed Central

    Gao, Yang; O'Caoimh, Rónán; Healy, Liam; Kerins, David M; Eustace, Joseph; Guyatt, Gordon; Sammon, David; Molloy, D William

    2013-01-01

    Objectives There is growing evidence that antihypertensive agents, particularly centrally acting ACE inhibitors (CACE-Is), which cross the blood–brain barrier, are associated with a reduced rate of cognitive decline. Given this, we compared the rates of cognitive decline in clinic patients with dementia receiving CACE-Is (CACE-I) with those not currently treated with CACE-Is (NoCACE-I), and with those who started CACE-Is, during their first 6 months of treatment (NewCACE-I). Design Observational case–control study. Setting 2 university hospital memory clinics. Participants 817 patients diagnosed with Alzheimer's disease, vascular or mixed dementia. Of these, 361 with valid cognitive scores were included for analysis, 85 CACE-I and 276 NoCACE-I. Measurements Patients were included if the baseline and end-point (standardised at 6 months apart) Standardised Mini-Mental State Examination (SMMSE) or Quick Mild Cognitive Impairment (Qmci) scores were available. Patients with comorbid depression or other dementia subtypes were excluded. The average 6-month rates of change in scores were compared between CACE-I, NoCACE-I and NewCACE-I patients. Results When the rate of decline was compared between groups, there was a significant difference in the median, 6-month rate of decline in Qmci scores between CACE-I (1.8 points) and NoCACE-I (2.1 points) patients (p=0.049), with similar, non-significant changes in SMMSE. Median SMMSE scores improved by 1.2 points in the first 6 months of CACE treatment (NewCACE-I), compared to a 0.8 point decline for the CACE-I (p=0.003) group and a 1 point decline for the NoCACE-I (p=0.001) group over the same period. Multivariate analysis, controlling for baseline characteristics, showed significant differences in the rates of decline, in SMMSE, between the three groups, p=0.002. Conclusions Cognitive scores may improve in the first 6 months after CACE-I treatment and use of CACE-Is is associated with a reduced rate of cognitive

  19. Trajectory of Cognitive Decline as a Predictor of Psychosis in Early Alzheimer Disease in the Cardiovascular Health Study

    PubMed Central

    Emanuel, James E.; Lopez, Oscar L.; Houck, Patricia R.; Becker, James T.; Weamer, Elise A.; DeMichele-Sweet, Mary Ann A.; Kuller, Lewis; Sweet, Robert A.

    2010-01-01

    Objective To compare the trajectories of cognitive decline between groups with, and without, the later development of psychotic symptoms during Alzheimer disease (AD) or Mild Cognitive Impairment (MCI). Design We examined cognitive function in a new analysis of an existing data set, The Cardiovascular Health Study (CHS), an epidemiologic, longitudinal follow-up study. Our analyses examined 9 years of follow-up data. Setting Community. Participants We examined subjects who were without dementia at study entry, received a diagnosis of AD or MCI during follow up and had been rated on the Neuropsychiatric Inventory for the presence of psychosis; 362 for the Modified Mini-Mental State Examination (3MS) analysis and 350 for the Digit Symbol Substitution Test (DSST) analysis had sufficient follow-up data and APOE genotyping. Measurements The 3MS and DSST were administered annually and analyzed using mixed effects models including APOE4 status. Results Mean 3MS and DSST scores did not differ between AD with psychosis and without psychosis groups at baseline. 3MS and DSST scores decreased more rapidly in subjects who ultimately developed psychosis. Conclusions Individuals who ultimately develop psychosis have more rapid cognitive deterioration during the earliest phases of AD than individuals with AD not developing psychosis. The genetic and other neurobiologic factors leading to the expression of AD+P may exert their effects via acceleration of the neurodegenerative process. PMID:20808116

  20. Use it or lose it! Cognitive activity as a protec-tive factor for cognitive decline associated with Alzheimer's disease.

    PubMed

    Mistridis, Panagiota; Mata, Jutta; Neuner-Jehle, Stefan; Annoni, Jean-Marie; Biedermann, Andreas; Bopp-Kistler, Irene; Brand, Dominique; Brioschi Guevara, Andrea; Decrey-Wick, Hedi; Démonet, Jean-François; Hemmeter, Ulrich; Kressig, Reto W; Martin, Brian; Rampa, Luca; Savaskan, Egemen; Stuck, Andreas; Tschopp, Philipp; Zekry, Dina; Monsch, Andreas

    2017-03-21

    Because of the worldwide aging of populations, Alzheimer's disease and other dementias constitute a devastating experience for patients and families as well as a major social and economic burden for both healthcare systems and society. Multiple potentially modifiable cardiovascular and lifestyle risk factors have been associated with this disease. Thus, modifying these risk factors and identifying protective factors represent important strategies to prevent and delay disease onset and to decrease the social burden. Based on the cognitive reserve hypothesis, evidence from epidemiological studies shows that low education and cognitive inactivity constitute major risk factors for dementia. This indicates that a cognitively active lifestyle may protect against cognitive decline or delay the onset of dementia. We describe a newly developed preventive programme, based on this evidence, to stimulate and increase cognitive activity in older adults at risk for cognitive decline. This programme, called "BrainCoach", includes the technique of "motivational interviewing" to foster behaviour change. If the planned feasibility study is successful, we propose to add BrainCoach as a module to the already existing "Health Coaching" programme, a Swiss preventive programme to address multiple risk factors in primary care.

  1. Brain reserve and cognitive decline: a non-parametric systematic review.

    PubMed

    Valenzuela, Michael J; Sachdev, Perminder

    2006-08-01

    A previous companion paper to this report (Valenzuela and Sachdev, Psychological Medicine 2006, 36, 441-454) suggests a link between behavioural brain reserve and incident dementia; however, the issues of covariate control and ascertainment bias were not directly addressed. Our aim was to quantitatively review an independent set of longitudinal studies of cognitive change in order to clarify these factors. Cohort studies of the effects of education, occupation, and mental activities on cognitive decline were of interest. Abstracts were identified in MEDLINE (1966-September 2004), CURRENT CONTENTS (to September 2004), PsychINFO (1984-September 2004), Cochrane Library Databases and reference lists from relevant articles. Eighteen studies met inclusion criteria. Key information was extracted by both reviewers onto a standard template with a high level of agreement. Cognitive decline studies were integrated using a non-parametric method after converting outcome data onto a common effect size metric. Higher behavioural brain reserve was related to decreased longitudinal cognitive decline after control for covariates in source studies (phi=1.70, p<0.001). This effect was robust to correction for both multiple predictors and multiple outcome measures and was the result of integrating data derived from more than 47000 individuals. This study affirms that the link between behavioural brain reserve and incident dementia is most likely due to fundamentally different cognitive trajectories rather than confound factors.

  2. Epidemiologic evidence of a relationship between tea, coffee, or caffeine consumption and cognitive decline.

    PubMed

    Arab, Lenore; Khan, Faraz; Lam, Helen

    2013-01-01

    A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men.

  3. Reduced information processing speed as primum movens for cognitive decline in MS.

    PubMed

    Van Schependom, Jeroen; D'hooghe, Marie B; Cleynhens, Krista; D'hooge, Mieke; Haelewyck, Marie-Claire; De Keyser, Jacques; Nagels, Guy

    2015-01-01

    Cognitive impairment affects half of the multiple sclerosis (MS) patient population and is an important contributor to patients' daily activities. Most cognitive impairment studies in MS are, however, cross-sectional or/and focused on the early disease stages. We aim to assess the time course of decline of different cognitive domains. We collected neuropsychological data on 514 MS patients to construct Kaplan-Meier survival curves of the tests included in the Neuropsychological Screening Battery for MS (NSBMS) and the Symbol Digit Modalities Test (SDMT). Cox-proportional hazard models were constructed to examine the influence of MS onset type, age at onset, gender, depression and level of education on the time course, expressed as age or disease. Survival curves of tests focusing on information processing speed (IPS) declined significantly faster than tests with less specific demands of IPS. Median age for pathological decline was 56.2 years (95% CI: 54.4-58.2) on the SDMT and 63.9 years (95% CI: 60-66.9) on the CLTR, a memory task. In conclusion, IPS is the cognitive domain not only most widely affected by MS but it is also the first cognitive deficit to emerge in MS. © The Author(s), 2015.

  4. Epidemiologic Evidence of a Relationship between Tea, Coffee, or Caffeine Consumption and Cognitive Decline12

    PubMed Central

    Arab, Lenore; Khan, Faraz; Lam, Helen

    2013-01-01

    A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men. PMID:23319129

  5. Use of the Internet as a prevention tool against cognitive decline in normal aging

    PubMed Central

    Klimova, Blanka

    2016-01-01

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed. PMID:27672317

  6. Periodic Limb Movements in Sleep are Associated with Greater Cognitive Decline in Older Men without Dementia

    PubMed Central

    Leng, Yue; Blackwell, Terri; Stone, Katie L.; Hoang, Tina D.; Redline, Susan; Yaffe, Kristine

    2016-01-01

    Study Objectives: To examine the association between periodic limb movements in sleep (PLMS) and change in selected aspects of cognition in community-dwelling older men. Methods: We studied 2,636 older men without dementia who underwent in-home polysomnography with measurement of the periodic limb movement index (PLMI) and periodic limb movement arousal index (PLMAI) using piezoelectric sensors. Random-effects models and logistic regression were used to examine the association between PLMI, PLMAI, and 3- to 4-y change in cognition. Results: After multivariable adjustment, men with a high PLMI had greater decline on the Trail Making Test – Part B (P trend = 0.02); those with a PLMI ≥ 30 were 48% more likely (odds ratio = 1.48, 95% confidence interval = 1.05–2.07) to experience the development of significant cognitive impairment (≥ 1 SD above mean change). Further adjustment for sleep efficiency, nocturnal hypoxemia, or dopaminergic medication use and analysis among men without Parkinson disease (n = 2,607) showed similar findings. No significant association was found for PLMAI or for Modified Mini-Mental State Examination scores. Conclusions: Among older men without dementia, higher PLMS frequency was associated with greater decline in cognition, particularly in executive function. Citation: Leng Y, Blackwell T, Stone KL, Hoang TD, Redline S, Yaffe K. Periodic limb movements in sleep are associated with greater cognitive decline in older men without dementia. SLEEP 2016;39(10):1807–1810. PMID:27568800

  7. Early development in Dravet syndrome; visual function impairment precedes cognitive decline.

    PubMed

    Chieffo, Daniela; Ricci, Daniela; Baranello, Giovanni; Martinelli, Diego; Veredice, Chiara; Lettori, Donatella; Battaglia, Domenica; Dravet, Charlotte; Mercuri, Eugenio; Guzzetta, Francesco

    2011-01-01

    Aim of the study was to describe prospectively the early neuropsychological evolution including the first pre-cognitive stages of the Severe Myoclonic Epilepsy in Infancy (SMEI) or Dravet syndrome. Five cases, four of whom since before a diagnostic evidence of the Dravet syndrome, were followed up. Full clinical assessment including developmental, visual function and behaviour assessments were serially performed. In four cases, a variable onset age of cognitive decline assessed with developmental scales was preceded some months before by an impairment of visual function; the remaining patient during all the course of follow-up till 51 months of age showed a normal development without visual impairment. A cognitive decline with variable onset was generally confirmed in Dravet syndrome. The previous early impairment of visual function seems to herald the cognitive decline and provides useful prognostic information; furthermore, it possibly suggests some clues for a better understanding of the mechanisms of cognitive deterioration in this syndrome. 2010 Elsevier B.V. All rights reserved.

  8. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.

    PubMed

    Oulhaj, Abderrahim; Jernerén, Fredrik; Refsum, Helga; Smith, A David; de Jager, Celeste A

    2016-01-01

    A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.

  9. Decline in cognitive function and elder mistreatment: findings from the Chicago Health and Aging Project.

    PubMed

    Dong, Xinqi; Simon, Melissa; Beck, Todd; Evans, Denis

    2014-06-01

    This study aimed to examine the longitudinal association between decline in cognitive function and elder mistreatment (EM). Chicago Health and Aging Project (CHAP) is an epidemiologic study conducted in a geographically defined community (N = 6,159). We identified 143 CHAP participants who had longitudinal cognitive data and EM reported to social services agency. The primary predictor was cognitive function, which was assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (Perceptual Speed), and both 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. Logistic regression models were used to assess the association of cognitive function domains and risk for EM. After adjusting for potential confounders, every one-point decline in global cognitive function (odds ratio [OR]: 1.57 [1.21-2.03]), MMSE (OR: 1.07 [1.03-1.10]), Episodic Memory (OR: 1.46 [1.14-1.86]), and Perceptual Speed (OR: 1.05 [1.02-1.07]) scores were associated with increased risk for EM. Lowest tertiles in global cognitive function (OR: 2.71 [1.49-4.88]), MMSE (OR: 2.02 [1.07-3.80]), Episodic Memory (OR: 2.70 [1.41-5.16]), and Perceptual Speed (OR: 4.41 [2.22-8.76]) scores were associated with increased risk for EM. Decline in global cognitive function, MMSE, and Perceptual Speed scores were associated with increased risk for EM. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research.

  11. Seafood types and age-related cognitive decline in the Women's Health Study.

    PubMed

    Kim, Dae Hyun; Grodstein, Francine; Rosner, Bernard; Kang, Jae H; Cook, Nancy R; Manson, Joann E; Buring, Julie E; Willett, Walter C; Okereke, Olivia I

    2013-10-01

    Seafood consumption may prevent age-related cognitive decline. However, benefits may vary by nutrient contents in different seafood types. We examined associations between total seafood consumption and cognitive decline and whether these associations differ by seafood types. We conducted a prospective cohort study of 5,988 women (mean age, 72 years) from the Women's Health Study who self-reported seafood intake at Women's Health Study baseline and also participated in telephone assessments of general cognition, verbal memory, and category fluency administered 5.6 years after Women's Health Study baseline and 2 and 4 years thereafter. Primary outcomes were standardized composite scores of global cognition and verbal memory. After adjusting for potential confounders, different amounts of total seafood consumption were not associated with changes in global cognition (p = .56) or verbal memory (p = .29). Considering seafood types, however, compared with women consuming less than once-weekly tuna or dark-meat finfish, those with once-weekly or higher consumption had significantly better verbal memory (0.079 standard units; p < .01) after 4 years-a difference comparable to that for women 2.1 years apart in age. There was also a statistically nonsignificant suggestion of better global cognition (p = .13) with once-weekly or higher tuna or dark-meat fish consumption. No significant associations were observed for light-meat finfish or shellfish. The relation of seafood to cognition may depend on the types consumed. Total consumption levels of seafood were unrelated to cognitive change. However, consumption of tuna and dark-meat fish once weekly or higher was associated with lower decline in verbal memory for a period of 4 years.

  12. Seafood Types and Age-Related Cognitive Decline in the Women’s Health Study

    PubMed Central

    2013-01-01

    Background. Seafood consumption may prevent age-related cognitive decline. However, benefits may vary by nutrient contents in different seafood types. We examined associations between total seafood consumption and cognitive decline and whether these associations differ by seafood types. Methods. We conducted a prospective cohort study of 5,988 women (mean age, 72 years) from the Women’s Health Study who self-reported seafood intake at Women’s Health Study baseline and also participated in telephone assessments of general cognition, verbal memory, and category fluency administered 5.6 years after Women’s Health Study baseline and 2 and 4 years thereafter. Primary outcomes were standardized composite scores of global cognition and verbal memory. Results. After adjusting for potential confounders, different amounts of total seafood consumption were not associated with changes in global cognition (p = .56) or verbal memory (p = .29). Considering seafood types, however, compared with women consuming less than once-weekly tuna or dark-meat finfish, those with once-weekly or higher consumption had significantly better verbal memory (0.079 standard units; p < .01) after 4 years—a difference comparable to that for women 2.1 years apart in age. There was also a statistically nonsignificant suggestion of better global cognition (p = .13) with once-weekly or higher tuna or dark-meat fish consumption. No significant associations were observed for light-meat finfish or shellfish. Conclusions. The relation of seafood to cognition may depend on the types consumed. Total consumption levels of seafood were unrelated to cognitive change. However, consumption of tuna and dark-meat fish once weekly or higher was associated with lower decline in verbal memory for a period of 4 years. PMID:23554464

  13. Trajectories of dementia-related cognitive decline in a large mental health records derived patient cohort

    PubMed Central

    Broadbent, Matthew; Shetty, Hitesh; Dobson, Richard J. B.

    2017-01-01

    Background Modeling trajectories of decline can help describe the variability in progression of cognitive impairment in dementia. Better characterisation of these trajectories has significant implications for understanding disease progression, trial design and care planning. Methods Patients with at least three Mini-mental State Examination (MMSE) scores recorded in the South London and Maudsley NHS Foundation Trust Electronic Health Records, UK were selected (N = 3441) to form a retrospective cohort. Trajectories of cognitive decline were identified through latent class growth analysis of longitudinal MMSE scores. Demographics, Health of Nation Outcome Scales and medications were compared across trajectories identified. Results Four of the six trajectories showed increased rate of decline with lower baseline MMSE. Two trajectories had similar initial MMSE scores but different rates of decline. In the faster declining trajectory of the two, a higher incidence of both behavioral problems and sertraline prescription were present. Conclusions We find suggestive evidence for association of behavioral problems and sertraline prescription with rate of decline. Further work is needed to determine whether trajectories replicate in other datasets. PMID:28591196

  14. 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.

  15. Is there an association between low-to-moderate alcohol consumption and risk of cognitive decline?

    PubMed

    Lobo, Elena; Dufouil, Carole; Marcos, Guillermo; Quetglas, Bernardo; Saz, Pedro; Guallar, Eliseo; Lobo, Antonio

    2010-09-15

    The authors evaluated the association of low-to-moderate alcohol consumption with risk of cognitive decline in a census-based cohort study of men and women aged ≥55 years conducted in Zaragoza, Spain (1994-1999). Participants free of dementia at baseline (N = 3,888) were examined after 2.5 and 4.5 years of follow-up. Information on alcohol intake was collected with the EURODEM Risk Factors Questionnaire and the History and Aetiology Schedule. The study endpoint was severe cognitive decline, defined as loss of ≥1 point/year on the Mini-Mental State Examination or a diagnosis of incident dementia (Diagnostic and Statistical Manual of Mental Disorders: DSM-IV, Text Revision criteria). Compared with those for abstainers, the multivariate-adjusted odds ratios for severe cognitive decline for male drinkers of <12 g alcohol/day, drinkers of 12-24 g alcohol/day, and former drinkers were 0.61 (95% confidence interval (CI): 0.31, 1.20), 1.19 (95% CI: 0.61, 2.32), and 1.03 (95% CI: 0.59, 1.82), respectively. The corresponding odds ratios for women were 0.88 (95% CI: 0.45, 1.72), 2.38 (95% CI: 0.98, 5.77), and 1.03 (95% CI: 0.48, 2.23). This study did not support the hypothesis that low-to-moderate alcohol consumption prevents cognitive decline. The inverse association between low-to-moderate alcohol intake and cognitive decline observed in other studies may have been due to inclusion of former drinkers in the abstainers reference category.

  16. A model of cognitive decline and suicidal ideation in adults aging with HIV.

    PubMed

    Vance, David E; Ross, Jill A; Moneyham, Linda; Farr, Kenneth F; Fordham, Pam

    2010-06-01

    The number of older adults with HIV continues to grow primarily because of the effectiveness of highly active antiretroviral therapy. Despite this welcomed benefit from pharmaceutical advances, aging with this disease presents an entirely new set of problems. The combination of aging and HIV can create a variety of stressors that may weaken one's resolve and further debilitate already compromised cognitive systems, which may increase rates of depression, suicidal ideation, and suicide. Studies indicate that older adults with HIV experience higher levels of depression and suicidal ideation than other older adults do or than younger adults with HIV do. Cognitive declines associated with both HIV and aging may provide insight into this phenomenon. A model of cognitive decline and suicidal ideation in adults aging with HIV is provided. Implications for nursing practice and research are discussed.

  17. Problems meeting basic needs predict cognitive decline in community-dwelling Hispanic older adults.

    PubMed

    Sachs-Ericsson, Natalie; Corsentino, Elizabeth; Cougle, Jesse R

    2009-09-01

    Objectives. Indices of low socioeconomic status (SES) have been found to predict negative health outcomes. However, problems meeting basic needs (e.g., not having enough money for health care, adequate food, etc.) may be a more potent measure of negative health outcomes than other more typically assessed indices of SES, such as income. This article examined the association between problems meeting basic needs and cognitive decline in a sample of community-dwelling Hispanic older adults (N = 1,964). Method. The authors used a prospective design to study the influence of problems meeting basic needs on cognitive functioning. Analyses controlled for demographics, health problems, and depressive symptoms. Results. The authors found problems meeting basic needs to be a more potent predictor of cognitive decline than income. Discussion. Interventions focused on providing older adults with resources for meeting basic needs, such as adequate food and health care, may substantially reduce the subsequent level of stress and health problems in this population.

  18. Gender Differences in Tea, Coffee, and Cognitive Decline in the Elderly: The Cardiovascular Health Study

    PubMed Central

    Arab, Lenore; Biggs, Mary L.; O’Meara, Ellen S.; Longstreth, W.T.; Crane, Paul K.; Fitzpatrick, Annette L.

    2013-01-01

    Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually by an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study. PMID:21841254

  19. Gender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study.

    PubMed

    Arab, Lenore; Biggs, Mary L; O'Meara, Ellen S; Longstreth, W T; Crane, Paul K; Fitzpatrick, Annette L

    2011-01-01

    Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.

  20. The 12 Years Preceding Mild Cognitive Impairment Due to Alzheimer’s Disease: The Temporal Emergence of Cognitive Decline

    PubMed Central

    Mistridis, Panagiota; Krumm, Sabine; Monsch, Andreas U.; Berres, Manfred; Taylor, Kirsten I.

    2015-01-01

    Abstract Background: The identification of the type and sequence of cognitive decline in preclinical mild cognitive impairment (MCI) prior to Alzheimer’s disease (AD) is crucial for understanding AD pathogenesis and implementing therapeutic interventions. Objective: To model the longitudinal courses of different neuropsychological functions in MCI due to AD. Methods: We investigated the prodromal phase of MCI over a 12-year period in 27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60 demographically matched healthy individuals (NC-NC). The longitudinal courses of cognitive performance (verbal and visual episodic memory, semantic memory, executive functioning, constructional praxis, psychomotor speed, language, and informant-based reports) were analyzed with linear mixed effects models. Results: The sequence with which different cognitive functions declined in the NC-MCI relative to the NC-NC group began with verbal memory and savings performance approximately eight years, and verbal episodic learning, visual memory, and semantic memory (animal fluency) circa four years prior to the MCI diagnosis. Executive functioning, psychomotor speed, and informant-based reports of the NC-MCI group declined approximately two years preceding the MCI diagnosis. Conclusions: Measurable neuropsychological deterioration occurs up to approximately eight years preceding MCI due to AD. PMID:26402083

  1. Vitamin D as a marker of cognitive decline in elderly Indian population

    PubMed Central

    Vedak, Tejal Kanhaiya; Ganwir, Vaishali; Shah, Arun B.; Pinto, Charles; Lele, Vikram R.; Subramanyam, Alka; Shah, Hina; Deo, Sudha Shrikant

    2015-01-01

    Objectives: Very few studies in India have addressed the role of vitamin D in cognitive function. The present study was conducted to assess the serum levels of 25-hydroxyvitamin D (25(OH)D) and its association with markers of cognitive impairment and homocysteine levels in the elderly Indian population. Materials and Methods: The study population consisted of patients with dementia (Group A, n = 32), mild cognitive impairment (MCI; Group B, n = 24), and elderly age-matched controls (Group C, n = 30). Measurement of serum levels of 25(OH)D and total homocysteine were done. Results: Significant decreased concentration of 25(OH)D and increased concentration of homocysteine was observed. Association of serum levels of vitamin D with markers of cognitive decline as well as serum homocysteine levels was observed in patients with dementia and MCI when compared to controls. Conclusion: Correlation of vitamin D with markers of cognitive decline and homocysteine opens a new door for early diagnosis of cognitive impairment. PMID:26425010

  2. 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.

  3. Can Training in a Real-Time Strategy Videogame Attenuate Cognitive Decline in Older Adults?

    PubMed Central

    Basak, Chandramallika; Boot, Walter R.; Voss, Michelle W.; Kramer, Arthur F.

    2014-01-01

    Declines in various cognitive abilities, particularly executive control functions, are observed in older adults. An important goal of cognitive training is to slow or reverse these age-related declines. However, opinion is divided in the literature regarding whether cognitive training can engender transfer to a variety of cognitive skills in older adults. Yet, recent research indicates that videogame training of young adults may engender broad transfer to skills of visual attention. In the current study, we used a real-time strategy videogame to attempt to train executive functions in older adults, such as working memory, task switching, short-term memory, inhibition, and reasoning. Older adults were either trained in a real-time strategy videogame for 23.5 hours (RON, n=20) or not (CONTROLS, n=20). A battery of cognitive tasks, including tasks of executive control and visuo-spatial skills, were assessed before, during, and after video game training. The trainees improved significantly in the measures of game performance. They also improved significantly more than the controls in a subset of the cognitive tasks, such as task switching, working memory, visual short term memory, and mental rotation. Trends in improvement were also observed, for the video game trainees, in inhibition and reasoning. Individual differences in changes in game performance were correlated with improvements in task-switching. The study has implications for the enhancement of executive control processes of older adults. PMID:19140648

  4. Sleep quality and cognitive decline in a community of older adults in Daqing City, China.

    PubMed

    Niu, Jinya; Han, Huijun; Wang, Yanhong; Wang, Li; Gao, Xiang; Liao, Susu

    2016-01-01

    To examine the association between self-reported sleep quality and cognitive decline one year later. A longitudinal study of 1010 cognitively intact adults, aged 65-80 years at baseline, from two urban communities in China was performed. Sleep quality at baseline was measured using the Pittsburgh Sleep Quality Index (PSQI). Cognitive function was determined by using the Chinese version of Mini-Mental State Examination (CMMSE) at the baseline and one year later. Substantial CMMSE decline was defined as the CMMSE score decreases by three or more points during the follow-up. Potential confounders, such as age, sex, education, baseline CMMSE score, depression, physical activity level, drinking status, smoking status, body mass index, snoring frequency, history of hypertension, diabetes, and coronary heart disease were measured via questionnaires or physical examination. After adjusting for potential confounders, individuals with poor sleep quality (PSQI > 7), relative to whose with good sleep quality, had 0.32 (95% CI: -0.62, -0.02; p = 0.04) CMMSE-points more decline and tended to have a higher likelihood of developing substantial CMMSE decline (OR = 1.46; 95% CI: 0.97, 2.18; p = 0.06). Among seven subscales of the PSQI, poor sleep efficiency was associated with greater CMMSE decline (beta = -0.16, 95% CI: -0.29, -0.03; p = 0.01) and higher risk of substantial CMMSE decline (OR = 1.24, 95% CI: 1.05, 1.46; p = 0.01). Short sleep duration (sleeping ≤5 h/night) was also significantly associated with more CMMSE decline and a higher likelihood of developing substantial CMMSE decline (p <0.05 for both). Self-reported poor sleep quality may be an indicator of early cognitive decline for elderly people and should be paid particular attention by clinicians. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Informants' Perception of Subjective Cognitive Decline Helps to Discriminate Preclinical Alzheimer's Disease from Normal Aging.

    PubMed

    Valech, Natalia; Mollica, María A; Olives, Jaume; Tort, Adriá; Fortea, Juan; Lleo, Alberto; Belén, Sánchez-Saudinós; Molinuevo, José Luis; Rami, Lorena

    2015-09-24

    Self-reported and informant-reported subjective cognitive decline (SCD) may be useful in the detection of preclinical Alzheimer's disease (Pre-AD) and cognitive impairment related to abnormal amyloid-β (Aβ 42) levels. a) To compare the Subjective Cognitive Decline Questionnaire (SCD-Q) ratings between Pre-AD subjects and cognitively healthy controls, b) to study the association of SCD-Q scores with levels of AD biomarkers in cognitively healthy and cognitively impaired subjects, and c) to compare SCD-Q ratings in cognitively impaired subjects with or without abnormal Aβ 42. Two hundred and seventeen participants (111 subjects; 106 informants) answered the SCD-Q. All subjects underwent a lumbar puncture to determine levels of Aβ 42 and tau, and an extensive neuropsychological battery. Healthy subjects were classified as Controls (CTR) or Pre-AD according to the absence or the presence of abnormal Aβ 42, and those with cognitive impairment (CI) into Non-amyloid (NonAB-CI) or Amyloid (AB-CI) impairment. Informants' SCD-Q scores were significantly higher in the Pre-AD group than in the CTR group (F = 6.75; p = 0.01). No significant differences were found in self-ratings. In the cognitively impaired groups, there were no significant differences in the SCD-Q ratings. In the whole sample, informants' ratings of SCD-Q correlated with Aβ 42 (r = -0.21; p = 0.02) and tau levels (r = 0.28; p = 0.00). Higher informants' ratings of SCD-Q differentiated Pre-AD subjects from CTR. Informants' ratings of SCD-Q correlated weakly with cerebrospinal fluid AD biomarkers.

  6. 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.

  7. Preventing Cognitive Decline in Older African Americans with Mild Cognitive Impairment: Design and Methods of a Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Leiby, Benjamin E.

    2012-01-01

    Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

  8. Preventing cognitive decline in older African Americans with mild cognitive impairment: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E

    2012-07-01

    Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Declining financial capacity in mild cognitive impairment: A 1-year longitudinal study.

    PubMed

    Triebel, K L; Martin, R; Griffith, H R; Marceaux, J; Okonkwo, O C; Harrell, L; Clark, D; Brockington, J; Bartolucci, A; Marson, Daniel C

    2009-09-22

    To investigate 1-year change in financial capacity in relation to conversion from amnestic mild cognitive impairment (MCI) to dementia. Seventy-six cognitively healthy older controls, 25 patients with amnestic MCI who converted to Alzheimer-type dementia during the study period (MCI converters), and 62 patients with MCI who did not convert to dementia (MCI nonconverters) were administered the Financial Capacity Instrument (FCI) at baseline and 1-year follow-up. Performance on the FCI domain and global scores was compared within and between groups using multivariate repeated-measures analyses. At baseline, controls performed better than MCI converters and nonconverters on almost all FCI domains and on both FCI total scores. MCI converters performed below nonconverters on domains of financial concepts, cash transactions, bank statement management, and bill payment and on both FCI total scores. At 1-year follow-up, MCI converters showed significantly greater decline than controls and MCI nonconverters for the domain of checkbook management and for both FCI total scores. The domain of bank statement management showed a strong trend. For both the checkbook and bank statement domains, MCI converters showed declines in procedural skills, such as calculating the correct balance in a checkbook register, but not in conceptual understanding of a checkbook or a bank statement. Declining financial skills are detectable in patients with mild cognitive impairment (MCI) in the year before their conversion to Alzheimer disease. Clinicians should proactively monitor patients with MCI for declining financial skills and advise patients and families about appropriate interventions.

  10. Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

    PubMed

    Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Viswanathan, Anand; Marshall, Gad A

    2015-01-01

    We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.

  11. NT-proBNP, blood pressure, and cognitive decline in the oldest old

    PubMed Central

    Sabayan, Behnam; Wijsman, Liselotte W.; Poortvliet, Rosalinde K.E.; Mooijaart, Simon P.; de Ruijter, Wouter; Gussekloo, Jacobijn; de Craen, Anton J.M.; Westendorp, R.G.J.

    2014-01-01

    Objective: To study the relation between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, used as a marker of heart failure in clinical practice, blood pressure (BP), and cognitive decline in the oldest old. Methods: In 560 participants of the Leiden 85-plus Study, we measured NT-proBNP levels and BP at age 85 years, at baseline, and global cognitive function (Mini-Mental State Examination [MMSE]) annually during the follow-up of 5 years. Results: Subjects in the highest tertile of NT-proBNP levels scored 1.7 points lower on the MMSE at age 85 years than subjects in the lowest tertile (p = 0.004), and had a 0.24-point-steeper decline in MMSE score per year (p = 0.021). The longitudinal association disappeared after full adjustment for possible confounders (0.14-point-steeper decline, p = 0.187). Subjects in the category “highest tertile of NT-proBNP and the lowest tertile of systolic BP” had a 3.7-point-lower MMSE score at baseline (p < 0.001) and a 0.49-point-steeper decline in MMSE score per year (p < 0.001) compared with subjects in the other categories. Conclusions: In the oldest old, high NT-proBNP levels are associated with lower MMSE scores. The combination of high NT-proBNP levels and low systolic BP is associated with worst global cognitive function and the steepest cognitive decline. Possibly, a failing pump function of the heart results in lower BP and lower brain perfusion with resultant brain dysfunction. PMID:25142900

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

    PubMed

    Mukadam, Naaheed; Jichi, Fatima; Green, David; Livingston, Gill

    2017-08-31

    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.

  13. Aging Exacerbates Obesity-induced Cerebromicrovascular Rarefaction, Neurovascular Uncoupling, and Cognitive Decline in Mice

    PubMed Central

    Tucsek, Zsuzsanna; Toth, Peter; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Warrington, Junie P.; Giles, Cory B.; Wren, Jonathan D.; Koller, Akos; Ballabh, Praveen; Sonntag, William E.; Csiszar, Anna

    2014-01-01

    Epidemiological studies show that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular impairment, we compared young (7 months) and aged (24 months) high-fat diet–fed obese C57BL/6 mice. We found that aging exacerbates the obesity-induced decline in microvascular density both in the hippocampus and in the cortex. The extent of hippocampal microvascular rarefaction and the extent of impairment of hippocampal-dependent cognitive function positively correlate. Aging exacerbates obesity-induced loss of pericyte coverage on cerebral microvessels and alters hippocampal angiogenic gene expression signature, which likely contributes to microvascular rarefaction. Aging also exacerbates obesity-induced oxidative stress and induction of NADPH oxidase and impairs cerebral blood flow responses to whisker stimulation. Collectively, obesity exerts deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular rarefaction and neurovascular uncoupling. The morphological and functional impairment of the cerebral microvasculature in association with increased blood–brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et al. Obesity in aging exacerbates blood–brain barrier disruption, neuroinflammation and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to obesity-induced cognitive decline in aging. PMID:24895269

  14. Longitudinal relationship of severe periodontitis with cognitive decline in older Japanese.

    PubMed

    Iwasaki, M; Yoshihara, A; Kimura, Y; Sato, M; Wada, T; Sakamoto, R; Ishimoto, Y; Fukutomi, E; Chen, W; Imai, H; Fujisawa, M; Okumiya, K; Taylor, G W; Ansai, T; Miyazaki, H; Matsubayashi, K

    2016-10-01

    Epidemiologic data examining the longitudinal relationship between periodontitis and cognitive status are very limited, especially in Asian populations. The present study examined the longitudinal relationship of periodontitis with cognitive decline in 85 Japanese community-dwelling individuals (average age: 79.3 years) for whom data were available from comprehensive health examinations conducted in 2010 and 2013. Based on a baseline full-mouth periodontal examination, severe periodontitis was defined using a Centers for Disease Control and Prevention/American Academy of Periodontology definition. Cognitive decline during the 3-year study period was defined using the results of the Mini-Mental State Examination (MMSE). Information on age, gender, education, depression, body mass index, smoking status, alcohol use, exercise, hypertension, diabetes, history of cardiovascular disease and stroke, and baseline MMSE scores were obtained and tested as potential confounders in the statistical models. Among 85 study participants, 21 (24.7%) were defined as having severe periodontitis. Multivariable Poisson regression analyses revealed that severe periodontitis was significantly associated with an increased risk of cognitive decline [adjusted relative risk = 2.2; 95% confidence interval (95% CI): 1.1-4.5]. Furthermore, multivariable linear regression analyses revealed that participants with severe periodontitis had a 1.8-point greater decrease (95% CI: -3.3 to -0.2) in MMSE score than those without severe periodontitis. Within the limitations related to its small sample size, the findings of the present study suggest that severe periodontitis is significantly associated with future decline in cognitive function among community-dwelling older Japanese subjects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Interleukin 6 Plasma Concentration Associates with Cognitive Decline: The Northern Manhattan Study

    PubMed Central

    Economos, Alexis; Wright, Clinton B.; Moon, Yeseon Park; Rundek, Tatjana; Rabbani, LeRoy; Paik, Myunghee C.; Sacco, Ralph L.; Elkind, Mitchell S. V.

    2013-01-01

    Background Interleukin 6 (IL-6) is an inflammatory cytokine that has been associated with vascular disease and cognitive impairment, but few studies have examined these relationships in population-based studies that include Hispanic white and black people who often have a greater prevalence of vascular risk factors and are at elevated risk of dementia. We examined relative elevations of plasma IL-6 concentrations in relation to cognitive decline in a stroke-free race/ethnically diverse community-based sample from Northern Manhattan. Methods We used mixed effects models to measure the effect of IL-6 on change in performance on the Telephone Interview for Cognitive Status (TICS-m) measured annually in our cohort, adjusting for sociodemographic and vascular risk factors. Results There were 1224 participants with IL-6 levels (median 1.5 pg/mL, interquartile range (IQR) 0.83 – 2.57 pg/mL) and TICS-m data available (mean=31.6 points, SD 6.5). The mean age was 71 (SD 9.3; 64% women, 59% Hispanic, 19% Black, 19% White) with 3,406 person- and a median 3.0 years of follow-up (IQR 1.1 – 4.0). Participants with IL-6 levels above the median showed greater cognitive decline on the TICS-m compared to those with levels below the median, adjusting for sociodemographic and vascular factors (β= −0.17 points per year, p=0.02). Decline on the TICS-m among participants with IL-6 above the median differed by age (P for interaction <0.001). There was no interaction by race-ethnicity, vascular risk factors, C-reactive protein (CRP), APOE4 allele status, or the metabolic syndrome among non-diabetics. Conclusions Interleukin 6 associated with cognitive decline among older participants in this race/ethnically diverse sample independent of other vascular risk factors and CRP. PMID:23364322

  16. Compensatory larger cortical thickness in healthy elderly individuals with electroencephalographic risk for cognitive decline.

    PubMed

    Castro-Chavira, Susana A; Barrios, Fernando A; Pasaye, Erick H; Alatorre-Cruz, Graciela C; Fernández, Thalía

    2016-06-15

    Excess theta electroencephalographic (EEG) activity has been described as an accurate predictor for cognitive decline at least 7 years before symptom presentation. To test whether this predictor for cognitive decline correlates with structural changes in the brains of healthy elderly individuals, we compared the magnetic resonance structural images of healthy individuals with excess of theta activity [group with a risk for cognitive decline, risk group (RG); n=14] with healthy controls with normal EEG activity (control group; n=14). Neuropsychological and epidemiological analyses showed significant differences in only two features: more years of education and better performance in the visuospatial process task in the control group. Voxel-based morphometry results were not conclusive, but showed tendencies toward larger volumes in the prefrontal and parietal lobes, and smaller volumes in the right temporal lobe, right occipital lobe, and left cerebellum for the RG; these tendencies are in agreement with those proposed by the posterior-anterior shift in an aging model. Cortical-thickness analyses yielded a significant correlation between cortical thickness and years of education in the prefrontal and inferior-temporal regions, and larger cortical thickness in the RG, independent of age and years of education, in the right superior temporal region. These results suggest changes in the cortical thickness of structures related to memory and visuospatial functions in healthy, cognitively normal individuals before the appearance of cognitive decline. Thus, the performance of healthy elderly individuals with EEG risk may only be slightly different from normal because of compensation mechanisms allowing them to fulfill daily-life tasks, masking structural changes during preclinical neurocognitive disorders.

  17. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  18. Does 8-foot walk time predict cognitive decline in older Mexicans Americans?

    PubMed

    Alfaro-Acha, Ana; Al Snih, Soham; Raji, Mukaila A; Markides, Kyriakos S; Ottenbacher, Kenneth J

    2007-02-01

    To examine the association between 8-foot time walk and change in cognitive function over time in older Mexican Americans. Data used are from the Hispanic Established Population for the Epidemiological Study of the Elderly (1993-2001). Five southwestern states: Texas, New Mexico, Colorado, Arizona, and California. Two thousand seventy noninstitutionalized Mexican-American men and women aged 65 and older who had a Mini-Mental State Examination (MMSE) score of 21 or greater at baseline. Sociodemographic factors (age, sex, education, marital status), MMSE score, 8-foot walk time, body mass index, medical conditions (stroke, heart attack, diabetes mellitus, depression, and hypertension), and near and distant visual impairment. Using general linear mixed models, it was found that subjects with the slowest 8-foot walk time had a significantly greater rate of cognitive decline over 7 years than subjects with the fastest 8-foot walk time. There was a significant 8-foot walk time-by-time interaction with MMSE scores. Subjects in the lowest 8-foot walk time quartile had a greater cognitive decline over 7 years (estimate=-0.32, SE=0.08; P<.001) than those in the highest quartile. This association remained statistically significant after controlling for potential confounding factors. Slow 8-foot walk time in older Mexican-American adults without cognitive impairment at baseline was an independent predictor of MMSE score decline over a 7-year period. Slow 8-foot walk time may be an early marker for older adults in a predementia state who may benefit from early-intervention programs to prevent or slow cognitive decline.

  19. Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease.

    PubMed

    Holmes, C; El-Okl, M; Williams, A L; Cunningham, C; Wilcockson, D; Perry, V H

    2003-06-01

    Activated microglia, the resident macrophages of the brain, are a feature of Alzheimer's disease. Animal models suggest that when activated microglia are further activated by a subsequent systemic infection this results in significantly raised levels of interleukin 1beta within the CNS, which may in turn potentiate neurodegeneration. This prospective pilot study in Alzheimer's disease subjects showed that cognitive function can be impaired for at least two months after the resolution of a systemic infection and that cognitive impairment is preceded by raised serum levels of interleukin 1beta. These relations were not confounded by the presence of any subsequent systemic infection or by baseline cognitive scores. Further research is needed to determine whether recurrent systemic infections drive cognitive decline in Alzheimer's disease subjects through a cytokine mediated pathway.

  20. Rate of cognitive decline in relation to sex after 60 years-of-age: a systematic review.

    PubMed

    Ferreira, Leandro; Ferreira Santos-Galduróz, Ruth; Ferri, Cleusa Pinheiro; Fernandes Galduróz, José Carlos

    2014-01-01

    Some studies have shown differences in specific cognitive ability domains between the sexes at 60 years-of-age. However is important to analyze whether the rate of cognitive decline is also similar between the sexes after this age. The present study examined previously published literature to investigate whether cognitive decline is distinct between men and women after the age of 60 years. A systematic review was carried out with the PubMed, LILACS and PsycINFO databases (2001-2011) using the following search terms: aging, aged, cognitive function, mild cognitive impairment, mental health and cognition. We analyzed longitudinal research that used neuropsychological tests for evaluating cognitive function, showed results separated by sex and that excluded participants with dementia. Elderly women showed better performance in tests of episodic memory, whereas elderly men had a better visuospatial ability. Only one study detected distinct rates of cognitive decline in specific tests between the sexes. Despite differences observed in some domains, most of the studies showed that this rate is similar between the sexes until the age of 80 years. It is unclear whether sex influences the rate of cognitive decline after the age of 80 years. The present review observed that sex does not determine the rate of cognitive decline between 60 and 80 years-of-age. The contextual and cultural factors that involve men and women might determine a distinct decline between them, rather than sex alone.

  1. Meditation and Music Improve Memory and Cognitive Function in Adults with Subjective Cognitive Decline: A Pilot Randomized Controlled Trial.

    PubMed

    Innes, Kim E; Selfe, Terry Kit; Khalsa, Dharma Singh; Kandati, Sahiti

    2017-01-01

    While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive, evidence suggests mind-body interventions may hold promise. In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer's disease. Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for 3 months, then at their discretion for the ensuing 3 months. At baseline, 3 months, and 6 months we measured memory and cognitive functioning [Memory Functioning Questionnaire (MFQ), Trail-making Test (TMT-A/B), and Digit-Symbol Substitution Test (DSST)]. The 6-month study was completed by 53 participants (88%). Participants performed an average of 93% (91% KK, 94% ML) of sessions in the first 3 months, and 71% (68% KK, 74% ML) during the 3-month, practice-optional, follow-up period. Both groups showed marked and significant improvements at 3 months in memory and cognitive performance (MFQ, DSST, TMT-A/B; p's≤0.04). At 6 months, overall gains were maintained or improved (p's≤0.006), with effect sizes ranging from medium (DSST, ML group) to large (DSST, KK group; TMT-A/B, MFQ). Changes were unrelated to treatment expectancies and did not differ by age, gender, baseline cognition scores, or other factors. Findings of this preliminary randomized controlled trial suggest practice of meditation or ML can significantly enhance both subjective memory function and objective cognitive performance in adults with SCD, and may offer promise for improving outcomes in this population.

  2. Cognitive decline and quality of life in incident Parkinson's disease: The role of attention.

    PubMed

    Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Breen, David P; Khoo, Tien K; Williams-Gray, Caroline H; Barker, Roger A; Collerton, Daniel; Taylor, John-Paul; Burn, David J

    2016-06-01

    Parkinson's disease dementia (PDD) is associated with poorer quality of life (QoL). Prior to the onset of PDD, many patients experience progressive cognitive impairment. There is a paucity of longitudinal studies investigating the effects of cognitive decline on QoL. This study aimed to determine the longitudinal impact of cognitive change on QoL in an incident PD cohort. Recently diagnosed patients with PD (n = 212) completed a schedule of neuropsychological assessments and QoL measures; these were repeated after 18 (n = 190) and 36 months (n = 158). Mild cognitive impairment (PD-MCI) was classified with reference to the Movement Disorder Society criteria. Principal component analysis was used to reduce 10 neuropsychological tests to three cognitive factors: attention, memory/executive function, and global cognition. Baseline PD-MCI was a significant contributor to QoL (β = 0.2, p < 0.01). For those subjects (9%) who developed dementia, cognitive function had a much greater impact on QoL (β = 10.3, p < 0.05). Multivariate modelling showed attentional deficits had the strongest predictive power (β = -2.3, p < 0.01); brief global tests only modestly predicted decline in QoL (β = -0.4, p < 0.01). PD-MCI was associated with poorer QoL over three years follow up. Cognitive impairment had a greater impact on QoL in individuals who developed dementia over follow-up. Impaired attention was a significant determinant of QoL in PD. Interventions which improve concentration and attention in those with PD could potentially improve QoL. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Continuous-flow cell saver reduces cognitive decline in elderly patients after coronary bypass surgery.

    PubMed

    Djaiani, George; Fedorko, Ludwik; Borger, Michael A; Green, Robin; Carroll, Jo; Marcon, Michael; Karski, Jacek

    2007-10-23

    Cerebral microembolization during cardiopulmonary bypass may lead to cognitive decline after cardiac surgery. Transfusion of the unprocessed shed blood (major source of lipid microparticulates) into the patient during cardiopulmonary bypass is common practice to reduce blood loss and blood transfusion. Processing of shed blood with cell saver before transfusion may limit cerebral microembolization and reduce cognitive decline after surgery. A total of 226 elderly patients were randomly allocated to either cell saver or control groups. Anesthesia and surgical management were standardized. Epiaortic scanning of the proximal thoracic aorta was performed in all patients. Transcranial Doppler was used to measure cerebral embolic rates. Standardized neuropsychological testing was conducted 1 week before and 6 weeks after surgery. The raw scores for each test were converted to Z scores, and then a combined Z score of 10 main variables was calculated for both study groups. The primary analysis was based on dichotomous composite cognitive outcome with a 1-SD rule. Cognitive dysfunction was present in 6% (95% confidence interval, 1.3% to 10.7%) of patients in the cell saver group and 15% (95% confidence interval, 8% to 22%) of patients in the control group 6 weeks after surgery (P=0.038). The severity of aortic atheroma and cerebral embolic count were similar between the 2 groups. The present report demonstrates that processing of shed blood with cell saver results in clinically significant reduction in postoperative cognitive dysfunction after cardiac surgery. These findings emphasize the clinical importance of lipid embolization in contributing to postoperative cognitive decline in patients exposed to cardiopulmonary bypass.

  4. Optimizing Cognitive Development over the Life Course and Preventing Cognitive Decline: Introducing the Cognitive Health Environment Life Course Model (CHELM)

    ERIC Educational Resources Information Center

    Anstey, Kaarin J.

    2014-01-01

    Optimal cognitive development is defined in this article as the highest level of cognitive function reached in each cognitive domain given a person's biological and genetic disposition, and the highest possible maintenance of cognitive function over the adult life course. Theoretical perspectives underpinning the development of a framework…

  5. Optimizing Cognitive Development over the Life Course and Preventing Cognitive Decline: Introducing the Cognitive Health Environment Life Course Model (CHELM)

    ERIC Educational Resources Information Center

    Anstey, Kaarin J.

    2014-01-01

    Optimal cognitive development is defined in this article as the highest level of cognitive function reached in each cognitive domain given a person's biological and genetic disposition, and the highest possible maintenance of cognitive function over the adult life course. Theoretical perspectives underpinning the development of a framework…

  6. Decreased Self-Appraisal Accuracy on Cognitive Tests of Executive Functioning Is a Predictor of Decline in Mild Cognitive Impairment

    PubMed Central

    Scherling, Carole S.; Wilkins, Sarah E.; Zakrezewski, Jessica; Kramer, Joel H.; Miller, Bruce L.; Weiner, Michael W.; Rosen, Howard J.

    2016-01-01

    Objective: Mild cognitive impairment (MCI) in older individuals is associated with increased risk of progression to dementia. The factors predicting progression are not yet well established, yet cognitive performance, particularly for memory, is known to be important. Anosognosia, meaning lack of awareness of one’s impaired function, is commonly reported in dementia and is often also a feature of MCI, but its association with risk of progression is not well understood. In particular, self-appraisal measures provide an autonomous measure of insight abilities, without the need of an informant. Methods: The present study examined the utility of self-appraisal accuracy at baseline for predicting cognitive decline in 51 patients using an informant-free assessment method. Baseline task performance scores were compared to self-assessments of performance to yield a discrimination score (DS) for tasks tapping into memory and executive functions. Results: Linear regression revealed that a larger DS for executive function tasks in MCI predicted functional decline, independent of age, education, and baseline memory and executive task scores. Conclusion: These findings indicate that objective estimates of self-appraisal can be used to quantify anosognosia and increase predictive accuracy for decline in MCI. PMID:27458368

  7. One-Carbon Metabolism Biomarkers and Cognitive Decline in the Very Old: The Newcastle 85+ Study.

    PubMed

    Mendonça, Nuno; Granic, Antoneta; Mathers, John C; Martin-Ruiz, Carmen; Wesnes, Keith A; Seal, Chris J; Jagger, Carol; Hill, Tom R

    2017-09-01

    Although the biological rationale for the association between folate, vitamin B12, and homocysteine with cognitive function seems plausible, conflicting results have been reported. This study aimed to determine the associations between 1-carbon (1-C) metabolism biomarkers (folate, vitamin B12, and homocysteine), and cognitive impairment at baseline and the rate of cognitive decline over 5 years in the very old. The Newcastle 85+ Study was a prospective longitudinal study of people 85 years old and followed over 5 years in Northeast England. Community-dwelling and institutionalized. The analytical sample included 765 very old participants with 1-C metabolism biomarkers and cognitive measures. Global cognition was measured by the Standardized Mini-Mental State Examination (SMMSE) at baseline, and at 3 and 5 years of follow-up and, attention-specific cognition with the Cognitive Drug Research (CDR) System at baseline, and at 1.5 and 3.0 years of follow-up. Baseline red blood cell folate (RBC folate), plasma vitamin B12, and total homocysteine (tHcy) concentrations were determined by immunoassay. Linear mixed models were used to estimate the associations between quartiles of 1-C metabolism biomarkers and cognition over 3 (CDR) and 5 years (SMMSE). Compared with participants in the lowest quartile of RBC folate concentrations (<612 nmol/L), those in the highest quartile of RBC folate concentrations (>1280 nmol/L) had 1 more point on the SMMSE at baseline (β = +1.02, SE = 0.43, P = .02). Those in quartile 4 of tHcy (>21.4 μmol/L) had 1 point less in the SMMSE at baseline than those in the lowest quartile (<13.5 μmol/L) (β = -1.05, SE = 0.46, P = .02). Plasma vitamin B12 was not predictive of global or attention-specific cognition at baseline and at follow-up. None of the 1-C metabolism biomarkers except tHcy was associated with the rate of decline in attention scores over 3 years. RBC folate and tHcy, but not plasma vitamin B12, were

  8. Sex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause

    PubMed Central

    2013-01-01

    Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality. Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men. The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age. Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely. PMID:23537114

  9. Attention capacity and self-report of subjective cognitive decline: a P3 ERP study.

    PubMed

    Smart, Colette M; Segalowitz, Sidney J; Mulligan, Bryce P; MacDonald, Stuart W S

    2014-12-01

    Subjective cognitive decline (SCD) has recently been proposed as the earliest stage of pathologic cognitive decline in older adults. Longitudinal research suggests that many individuals with SCD go on to develop mild cognitive impairment or Alzheimer's disease. However, those with SCD typically appear normal on standardized neuropsychological testing, and as of yet there are no reliable objective measures discriminating those with SCD from healthy peers. Two groups of healthy older adults (ages 65-80), who self-identified as being with (n=17) or without SCD (n=23), completed self-report measures and objective measures of cognition. Groups did not differ on demographic variables, estimated cognitive reserve, or clinical neuropsychological testing. However, self-identifying as having SCD predicted clear differences in the P3 event-related potential in response to an attention control task, over and above any contributions from mood, anxiety, or neuroticism. Results suggest that using direct neural measures of information processing might be useful where standardized clinical tools are insensitive in those with SCD.

  10. Can training in a real-time strategy video game attenuate cognitive decline in older adults?

    PubMed

    Basak, Chandramallika; Boot, Walter R; Voss, Michelle W; Kramer, Arthur F

    2008-12-01

    Declines in various cognitive abilities, particularly executive control functions, are observed in older adults. An important goal of cognitive training is to slow or reverse these age-related declines. However, opinion is divided in the literature regarding whether cognitive training can engender transfer to a variety of cognitive skills in older adults. In the current study, the authors trained older adults in a real-time strategy video game for 23.5 hr in an effort to improve their executive functions. A battery of cognitive tasks, including tasks of executive control and visuospatial skills, were assessed before, during, and after video-game training. The trainees improved significantly in the measures of game performance. They also improved significantly more than the control participants in executive control functions, such as task switching, working memory, visual short-term memory, and reasoning. Individual differences in changes in game performance were correlated with improvements in task switching. The study has implications for the enhancement of executive control processes of older adults.

  11. Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial.

    PubMed

    Leoutsakos, Jeannie-Marie S; Muthen, Bengt O; Breitner, John C S; Lyketsos, Constantine G

    2012-04-01

    We examined the effects of non-steroidal anti-inflammatory drugs on cognitive decline as a function of phase of pre-clinical Alzheimer disease. Given recent findings that cognitive decline accelerates as clinical diagnosis is approached, we used rate of decline as a proxy for phase of pre-clinical Alzheimer disease. We fit growth mixture models of Modified Mini-Mental State (3MS) Examination trajectories with data from 2388 participants in the Alzheimer's Disease Anti-inflammatory Prevention Trial and included class-specific effects of naproxen and celecoxib. We identified three classes: "no decline", "slow decline", and "fast decline", and examined the effects of celecoxib and naproxen on linear slope and rate of change by class. Inclusion of quadratic terms improved fit of the model (-2 log likelihood difference: 369.23; p < 0.001) but resulted in reversal of effects over time. Over 4 years, participants in the slow-decline class on placebo typically lost 6.6 3MS points, whereas those on naproxen lost 3.1 points (p-value for difference: 0.19). Participants in the fast-decline class on placebo typically lost 11.2 points, but those on celecoxib first declined and then gained points (p-value for difference from placebo: 0.04), whereas those on naproxen showed a typical decline of 24.9 points (p-value for difference from placebo: <0.0001). Our results appeared statistically robust but provided some unexpected contrasts in effects of different treatments at different times. Naproxen may attenuate cognitive decline in slow decliners while accelerating decline in fast decliners. Celecoxib appeared to have similar effects at first but then attenuated change in fast decliners. Copyright © 2011 John Wiley & Sons, Ltd.

  12. Vitamin D Levels and the Risk of Cognitive Decline in Chinese Elderly People: the Chinese Longitudinal Healthy Longevity Survey.

    PubMed

    Matchar, David B; Chei, Choy-Lye; Yin, Zhao-Xue; Koh, Victoria; Chakraborty, Bibhas; Shi, Xiao-Ming; Zeng, Yi

    2016-10-01

    Vitamin D has a neuroprotective function, potentially important for the prevention of cognitive decline. Prospective studies from Western countries support an association between lower vitamin D level and future cognitive decline in elderly people. No prospective study has examined this association in Asia. This community-based cohort study of elderly people in China follows 1,202 cognitively intact adults aged ≥60 years for a mean duration of 2 years. Plasma vitamin D level was measured at the baseline. Cognitive state of participants was assessed using the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as an MMSE score <18. Cognitive decline was defined as ≥3 points decline from baseline. Multivariable logistic regression models were used to examine the association between quartiles of vitamin D levels with cognitive decline and incidence of cognitive impairment. Participants with low vitamin D level had an increased risk of cognitive decline. Compared with the highest quartile of vitamin D levels, the multivariable odds ratios (ORs; 95% confidence interval) for cognitive decline were 2.1 (1.3-3.4) for the second highest quartile, 2.2 (1.4-3.6) for the third highest quartile, and 2.0 (1.2-3.3) for the lowest quartile. The multivariable ORs of incident cognitive impairment for the second highest, third highest, and lowest versus highest quartiles of vitamin D levels were 1.9 (0.9-4.1), 2.6 (1.2-5.6), and 3.2 (1.5-6.6), respectively. This first follow-up study of elderly people, including the oldest-old, in Asia shows that low vitamin D levels were associated with increased risk of subsequent cognitive decline and impairment. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Self-perceived Difficulties in Everyday Function Precede Cognitive Decline among Older Adults in the ACTIVE Study.

    PubMed

    Tomaszewski Farias, Sarah; Giovannetti, Tania; Payne, Brennan R; Marsiske, Michael; Rebok, George W; Schaie, K Warner; Thomas, Kelsey R; Willis, Sherry L; Dzierzewski, Joseph M; Unverzagt, Frederick; Gross, Alden L

    2017-08-11

    Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2017, 23, 1-9).

  14. 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

  15. Neuropsychological Markers of Cognitive Decline in Persons With Alzheimer Disease Neuropathology.

    PubMed

    Hassenstab, Jason; Monsell, Sarah E; Mock, Charles; Roe, Catherine M; Cairns, Nigel J; Morris, John C; Kukull, Walter

    2015-11-01

    To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropathology at autopsy, we examined neuropsychological performance in cognitively healthy (Clinical Dementia Rating [CDR] = 0) participants who returned for at least 1 follow-up and died within 2 years of their last assessment. Nonprogressors remained at CDR = 0 until death; progressors developed symptomatic AD during life (CDR > 0). Cognitive performance at baseline was compared between progressors and nonprogressors on a global cognitive composite and 4 domain-specific composites (episodic memory, language, attention/working memory, and executive function). Models adjusted for age, education, sex, and non-AD neuropathology. Progressors (n = 173) had worse performance than nonprogressors (n = 141) in nearly all cognitive domains. Progressors scored lower on composites of global cognition (P < 0.001), executive function (P = 0.0006), language (P < 0.0001), and episodic memory (P = 0.0006) but not on attention/working memory (P = 0.91). These data indicate that individuals with underlying AD neuropathology who are clinically healthy but who later develop symptomatic AD have worse performance in a wide range of domains versus individuals with underlying AD neuropathology who are clinically healthy but do not become symptomatic during life. Therefore, subtle cognitive decline at baseline may indicate an increased risk of progression to symptomatic AD.

  16. 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.

  17. 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.

  18. Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline.

    PubMed

    Chen, Liuji; Na, Ren; Ran, Qitao

    2014-11-01

    Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17-19 months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling. Published by Elsevier Inc.

  19. Adverse Vascular Risk is Related to Cognitive Decline in Older Adults

    PubMed Central

    Jefferson, Angela L.; Hohman, Timothy J.; Liu, Dandan; Haj-Hassan, Shereen; Gifford, Katherine A.; Benson, Elleena M.; Skinner, Jeannine S.; Lu, Zengqi; Sparling, Jamie; Sumner, Emily C.; Bell, Susan; Ruberg, Frederick L.

    2014-01-01

    Background Cardiovascular disease (CVD) and related risk factors are associated with Alzheimer’s disease (AD). This association is less well-defined in normal cognition (NC) or prodromal AD (mild cognitive impairment (MCI)). Objective Cross-sectionally and longitudinally relate a vascular risk index to cognitive outcomes among elders free of clinical dementia. Methods 3117 MCI (74±8 years, 56% female) and 6603 NC participants (72±8 years, 68% female) were drawn from the National Alzheimer’s Coordinating Center. A composite measure of vascular risk was defined using the Framingham Stroke Risk Profile (FSRP) score (i.e., age, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, CVD history, atrial fibrillation). Ordinary linear regressions and generalized linear mixed models related baseline FSRP to cross-sectional and longitudinal cognitive outcomes, separately for NC and MCI, adjusting for age, sex, race, education, and follow-up time (in longitudinal models). Results In NC participants, increasing FSRP was related to worse baseline global cognition, information processing speed, and sequencing abilities (p-values<0.0001) and a worse longitudinal trajectory on all cognitive measures (p-values<0.0001). In MCI, increasing FSRP correlated with worse longitudinal delayed memory (p=0.004). In secondary models using an age-excluded FSRP score, associations persisted in NC participants for global cognition, naming, information processing speed, and sequencing abilities. Conclusions An adverse vascular risk profile is associated with worse cognitive trajectory, especially global cognition, naming, and information processing speed, among NC elders. Future studies are needed to understand how effective management of CVD and related risk factors can modify cognitive decline to identify the ideal timeframe for primary prevention implementation. PMID:25471188

  20. Cancer, Coping, and Cognition: A Model for the Role of Stress Reactivity in Cancer-Related Cognitive Decline

    PubMed Central

    Andreotti, Charissa; Root, James C.; Ahles, Tim A.; McEwen, Bruce S.; Compas, Bruce E.

    2014-01-01

    Cognitive decline and accompanying neurological changes associated with non-CNS cancer diagnosis and treatment have been increasingly identified in a subset of patients. Initially believed to be due to neurotoxic effects of chemotherapy exposure, observation of cognitive decline in patients not treated with chemotherapy, cancer-diagnosed individuals prior to treatment, and patients receiving alternative treatment modalities (surgery, endocrine therapy, radiation), has led to investigation of additional potential etiologies and moderating factors. Stressful experiences have long been posited as a contributor to these cognitive changes. Through reciprocal connectivity with peripheral systems, the brain maintains a dynamic circuitry to adapt to stress (allostasis). However, overuse of this system leads to dysregulation and contributes to pathophysiology (allostatic load). At this time, little research has been conducted to systematically examine the role of allostatic load in cancer-related cognitive dysfunction. Here we integrate theories of stress biology, neuropsychology, and coping and propose a model through which individuals with a high level of allostatic load at diagnosis may be particularly vulnerable to the neurocognitive effects of cancer. Opportunities for future research to test and extend proposed mechanisms are discussed in addition to points of prevention and intervention based on individual variation in stress reactivity and coping skills. PMID:25286084

  1. The influence of vascular risk factors on cognitive decline in patients with Alzheimer's disease.

    PubMed

    Blom, Kim; Vaartjes, Ilonca; Peters, Sanne A E; Koek, Huiberdina L

    2014-09-01

    The influence of vascular risk factors (VRFs) on the rate of cognitive decline in patients with established dementia is unclear. This study aims to examine the association between VRFs and the rate of cognitive decline in patients with Alzheimer's disease (AD). Data were obtained from patients visiting a memory clinic between 2004 and 2012. VRFs were determined at baseline and included hypertension, hypercholesterolemia, diabetes mellitus, overweight and smoking. Continuous values of blood pressure, total cholesterol, glucose level and body mass index were also obtained. Mini-Mental State Exam (MMSE) scores were obtained at baseline and during follow-up visits. The association between VRFs and the annual change in MMSE scores was analysed with a multivariable linear mixed model adjusted for age, sex and the aforementioned VRFs. From 174 patients (mean age 78.3 years), with a follow-up time up to 5.8 years (mean 1.1 year), in total 447 MMSE scores were obtained. The multivariable analyses showed an association between age as well as systolic blood pressure and a decline in annual rates of change in MMSE scores of -0.05 (95% confidence interval (CI): -0.09 to 0.00) and -0.01 (CI: -0.03 to 0.00), respectively. For all other VRFs, including sex, patients did not show a significant difference. This study did not find an association between preventable vascular risk factors and cognitive decline in patients with AD, except for systolic blood pressure. As the association between systolic blood pressure and decline in MMSE was small, clinical relevance may be limited. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study

    NASA Astrophysics Data System (ADS)

    Kent, Shia T.; Kabagambe, Edmond K.; Wadley, Virginia G.; Howard, Virginia J.; Crosson, William L.; Al-Hamdan, Mohammad Z.; Judd, Suzanne E.; Peace, Fredrick; McClure, Leslie A.

    2014-04-01

    Sunlight may be related to cognitive