Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936

INTRODUCTION: Plasma phospho-tau 181 (p-tau181) is a promising blood biomarker for Alzheimer's disease. However, its predictive validity for age-related cognitive decline without dementia remains unclear. Several forms of p-tau have been shown to contribute to synapse degeneration, but it is unknown whether p-tau181 is present in synapses. Here, we tested whether plasma p-tau181predicts cognitive decline and whether it is present in synapses in human brain. METHODS: General cognitive ability and plasma p-tau181 concentration were measured in 195 participants at ages 72 and 82. Levels of p-tau181 in total homogenate and synaptic fractions were compared with western blot (n=10-12 per group), and synaptic localisation was examined using array tomography. RESULTS: Elevated baseline plasma p-tau181 and increasing p-tau181 over time predicted steeper general cognitive decline. We observe p-tau181 in neurites, presynapses, and post-synapses in the brain. DISCUSSION: Baseline and subsequent change in plasma p-tau181 may represent rare biomarkers of differences in cognitive ageing across the 8th decade of life and may play a role in synaptic function in the brain.

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Cognitive change before old age (11 to 70) predicts cognitive change after old age (70 to 82)

10.31234/osf.io/h8739 ◽

2021 ◽

Author(s):

Federica Conte ◽

Judith Okely ◽

Olivia Hamilton ◽

Janie Corley ◽

Danielle Page ◽

...

Keyword(s):

Cognitive Decline ◽

Old Age ◽

Social Impact ◽

Adult Life ◽

Cognitive Change ◽

Older Age ◽

Growth Curve Models ◽

Age Related ◽

Lothian Birth Cohort ◽

Age Related Cognitive Decline

Identifying predictors of cognitive decline within older age helps to understand its mechanisms and to identify those at greater risk. Here we examine how cognitive change from 11 to 70 years is associated with cognitive change within older age (70 to 82 years) in the Lothian Birth Cohort 1936 longitudinal study (N=1091 at recruitment). Using latent growth curve models, we estimate rates of change from age 70 to 82 in general cognitive ability (g) and in three cognitive domains: visuospatial, memory and processing speed. g accounted for 71.3% of interindividual change variance. Greater 11-70 cognitive gain predicted slower decline in g over 12 subsequent years (β = .163, p = .001), independently of cognitive level at age 70, and domain-specific change beyond g. These results contribute toward identifying people at higher risk of age-related cognitive decline. Age-related cognitive decline is a significant threat to the quality of life in older age. Its economic and social impact on society will increase together with the steadily rising life expectancy. How can we preserve cognitive health in older age? Researchers have made significant advances in identifying protective and risk factors. However, most studies focus on a limited age range, and cognitive change mechanisms are not yet completely understood. This work takes advantage of almost life-spanning longitudinal data to test if cognitive trajectory across childhood and adulthood can predict cognitive trajectories in older age. Our findings show that earlier change is associated with later change. Some factors related to individual differences in cognitive change might thus operate over much of the adult life course, and certainly before older age. This knowledge can help identify individuals at higher risk of decline and understand the mechanisms and factors responsible.

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Lifelong environmental enrichment in the absence of exercise protects the brain from age-related cognitive decline

Neuropharmacology ◽

10.1016/j.neuropharm.2018.03.042 ◽

2019 ◽

Vol 145 ◽

pp. 59-74 ◽

Cited By ~ 17

Author(s):

Amy M. Birch ◽

Áine M. Kelly

Keyword(s):

Cognitive Decline ◽

Environmental Enrichment ◽

Age Related ◽

Age Related Cognitive Decline ◽

The Brain

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

Molecular Psychiatry ◽

10.1038/mp.2010.137 ◽

2011 ◽

Vol 17 (3) ◽

pp. 315-324 ◽

Cited By ~ 97

Author(s):

O J G Schiepers ◽

S E Harris ◽

A J Gow ◽

A Pattie ◽

C E Brett ◽

...

Keyword(s):

Cognitive Decline ◽

Birth Cohort ◽

Age Related ◽

Lothian Birth Cohort ◽

Age Related Cognitive Decline

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Interleukin 6 reduces allopregnanolone synthesis in the brain and contributes to age-related cognitive decline in mice

The Journal of Lipid Research ◽

10.1194/jlr.ra119000479 ◽

2020 ◽

Vol 61 (10) ◽

pp. 1308-1319

Author(s):

Eileen E. Parks ◽

Sreemathi Logan ◽

Alexander Yeganeh ◽

Julie A. Farley ◽

Daniel B. Owen ◽

...

Keyword(s):

Cognitive Function ◽

Cognitive Decline ◽

Inflammatory Cytokines ◽

Interleukin 6 ◽

Age Related ◽

Natural Inhibitor ◽

Age Related Cognitive Decline ◽

The Brain

Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain. We assessed the levels and regulation of AlloP and the effects of AlloP supplementation on cognitive function in 4-month-old and 24-month-old male C57BL/6 mice. With age, the expression of enzymes involved in the AlloP synthetic pathway was decreased and corticosterone (CORT) synthesis increased. Supplementation of AlloP improved cognitive function. Interestingly, interleukin 6 (IL-6) infusion in young animals significantly reduced the production of AlloP compared with controls. It is notable that inhibition of IL-6 with its natural inhibitor, soluble membrane glycoprotein 130, significantly improved spatial memory in aged mice. These findings were supported by in vitro experiments in primary murine astrocyte cultures, indicating that IL-6 decreases production of AlloP and increases CORT levels. Our results indicate that age-related increases in IL-6 levels reduce progesterone substrate availability, resulting in a decline in AlloP levels and an increase in CORT. Furthermore, our results indicate that AlloP is a critical link between inflammatory cytokines and the age-related decline in cognitive function.

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Preserved cognition and reduced age-related cognitive decline during treatment with angiotensin II receptor blockers: A 20-year follow-up study

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.386 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S372-S372 ◽

Cited By ~ 1

Author(s):

D. Wincewicz ◽

T. Tolmunen ◽

A.K. Brem ◽

J. Kauhanen ◽

S. Lehto

Keyword(s):

Angiotensin Ii ◽

Cognitive Decline ◽

Population Based ◽

Angiotensin Ii Receptor ◽

Cross Sectional ◽

Age Related ◽

Receptor Blockers ◽

Age Related Cognitive Decline ◽

The Brain

IntroductionModulators of the brain renin-angiotensin system (RAS) have been shown to improve cognitive functioning in several animal models of neuropsychiatric disorders. Moreover, the brain RAS has been considered a new target for the treatment of Alzheimer's disease (AD). However, there are no population-based follow-up studies supporting this hypothesis.ObjectivesCross-sectional and prospective relationships between cognitive decline and ARB treatment were examined in the population-based Kuopio Ischemic Heart Disease Risk Factor Study.AimsTo evaluate procognitive/antidementia capacity of orally delivered angiotensin II receptor blockers (ARB).MethodsThe study was conducted on a sample of 1774 subjects (920 females, 854 males; age range at baseline: 42–61 years) from Eastern Finland. An established cutoff score of at least 2-point decrease in the Mini Mental State Examination over a 9-year follow-up was used to detect age-related cognitive decline in the cross-sectional setting. In the prospective setting, a hospital discharge diagnosis of dementia/AD was used as outcome variable. Cross-sectional relationships were determined with logistic regression and prospective analyses were conducted with the Cox proportional hazards model (both adjusted for relevant background variables).ResultsCross-sectional analysis displayed a decrease of the odds of cognitive decline (n = 87; 4.9% of participants) in those with ARB treatment; OR = 0.445, 95% CI: 0.22–0.90, P = 0.024. Furthermore, in the prospective setting, the risk of dementia/AD diagnosis (n = 149; 8.4% of participants) was significantly reduced in ARB treated participants; HR = 0.621, 95% CI: 0.40–0.98, P = 0.038.ConclusionsARB treatment is associated with a decreased risk for age-related cognitive decline and dementia/AD manifestation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Genetic architecture of age-related cognitive decline in African Americans

Neurology Genetics ◽

10.1212/nxg.0000000000000125 ◽

2016 ◽

Vol 3 (1) ◽

pp. e125 ◽

Cited By ~ 13

Author(s):

Towfique Raj ◽

Lori B. Chibnik ◽

Cristin McCabe ◽

Andus Wong ◽

Joseph M. Replogle ◽

...

Keyword(s):

Risk Factors ◽

African Americans ◽

Cognitive Decline ◽

Genetic Risk ◽

Genetic Architecture ◽

Genetic Risk Factors ◽

Cognitive Change ◽

Age Related ◽

Age Related Cognitive Decline ◽

Shared Risk

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.

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Activity Engagement in Cognitive Aging: A Review of the Evidence

Perspectives on Neurophysiology and Neurogenic Speech and Language Disorders ◽

10.1044/nnsld23.1.35 ◽

2013 ◽

Vol 23 (1) ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

Yvonne Rogalski ◽

Muriel Quintana

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Cognitive Aging ◽

Social Activity ◽

Current Evidence ◽

Omega 3 ◽

Neuroprotective Effects ◽

Activity Engagement ◽

Age Related ◽

Age Related Cognitive Decline

The population of older adults is rapidly increasing, as is the number and type of products and interventions proposed to prevent or reduce the risk of age-related cognitive decline. Advocacy and prevention are part of the American Speech-Language-Hearing Association’s (ASHA’s) scope of practice documents, and speech-language pathologists must have basic awareness of the evidence contributing to healthy cognitive aging. In this article, we provide a brief overview outlining the evidence on activity engagement and its effects on cognition in older adults. We explore the current evidence around the activities of eating and drinking with a discussion on the potential benefits of omega-3 fatty acids, polyphenols, alcohol, and coffee. We investigate the evidence on the hypothesized neuroprotective effects of social activity, the evidence on computerized cognitive training, and the emerging behavioral and neuroimaging evidence on physical activity. We conclude that actively aging using a combination of several strategies may be our best line of defense against cognitive decline.

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