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

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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Impact of social network on cognitive performances and age-related cognitive decline across a 20-year follow-up

International Psychogeriatrics ◽

10.1017/s1041610211001165 ◽

2011 ◽

Vol 23 (9) ◽

pp. 1405-1412 ◽

Cited By ~ 23

Author(s):

Ralitsa Stoykova ◽

Fanny Matharan ◽

Jean-François Dartigues ◽

Hélène Amieva

Keyword(s):

Social Network ◽

Cognitive Decline ◽

Social Functioning ◽

Reverse Causality ◽

Neuropsychological Battery ◽

Age Related ◽

Social Network Satisfaction ◽

Age Related Cognitive Decline ◽

The Relationship

ABSTRACTBackground: The objective of this study was to investigate the relationship between social network and cognitive decline, taking into account the potential bias of reverse causality.Methods: The study sample comprised 2055 elderly participants without dementia. We assessed baseline social functioning across four variables: size of social network, satisfaction with relationships, perception of being understood, and participation in social activities. A neuropsychological battery was proposed at baseline and repeated throughout follow-up. Linear mixed models were used to investigate the relationship between social network and baseline cognitive performances and cognitive decline during the 20-year follow-up.Results: When controlling for the reverse causality bias by excluding participants who developed dementia during the study follow-up and after adjusting for covariates, the results showed that better social functioning at baseline was associated with better initial performances in the Isaacs Set Test and the Wechsler Paired Associate Test. However, there was no significant association with further cognitive decline. By contrast, when the bias of reverse causality was not controlled for (i.e. no exclusion of participants who developed dementia), the association between social network and global cognitive decline measured by MMSE was found to be statistically significant.Conclusion: With the opportunity to exclude participants who developed dementia, and the particularly long follow-up of participants, we were able to investigate the relationship between social networks and age-related cognitive decline with a minimization of reverse causality bias. The results suggest that even though higher social functioning is concomitantly associated with better cognitive performances, it may not prevent subsequent decline.

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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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Age‐related cognitive decline in myotonic dystrophy type 1: An 11‐year longitudinal follow‐up study

Journal of Neuropsychology ◽

10.1111/jnp.12192 ◽

2019 ◽

Vol 14 (1) ◽

pp. 121-134 ◽

Cited By ~ 1

Author(s):

Garazi Labayru ◽

Jone Aliri ◽

Miren Zulaica ◽

Adolfo López de Munain ◽

Andone Sistiaga

Keyword(s):

Cognitive Decline ◽

Myotonic Dystrophy ◽

Myotonic Dystrophy Type 1 ◽

Myotonic Dystrophy Type ◽

Follow Up Study ◽

Age Related ◽

Age Related Cognitive Decline

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Cataract surgery and age-related cognitive decline: A 13-year follow-up of the English Longitudinal Study of Ageing

PLoS ONE ◽

10.1371/journal.pone.0204833 ◽

2018 ◽

Vol 13 (10) ◽

pp. e0204833 ◽

Cited By ~ 14

Author(s):

Asri Maharani ◽

Piers Dawes ◽

James Nazroo ◽

Gindo Tampubolon ◽

Neil Pendleton ◽

...

Keyword(s):

Longitudinal Study ◽

Cognitive Decline ◽

Cataract Surgery ◽

Age Related ◽

Age Related Cognitive Decline ◽

English Longitudinal Study

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Correction: Cataract surgery and age-related cognitive decline: A 13-year follow-up of the English Longitudinal Study of Ageing

PLoS ONE ◽

10.1371/journal.pone.0208045 ◽

2018 ◽

Vol 13 (11) ◽

pp. e0208045 ◽

Cited By ~ 1

Author(s):

Asri Maharani ◽

Piers Dawes ◽

James Nazroo ◽

Gindo Tampubolon ◽

Neil Pendleton ◽

...

Keyword(s):

Longitudinal Study ◽

Cognitive Decline ◽

Cataract Surgery ◽

Age Related ◽

Age Related Cognitive Decline ◽

English Longitudinal Study

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White matter hyperintensities may be an early marker for age-related cognitive decline in the ADNI cohort

10.1101/2021.09.23.461560 ◽

2021 ◽

Author(s):

Cassandra Morrison ◽

Mahsa Dadar ◽

Sylvia Villeneuve ◽

D. Louis Collins

Keyword(s):

White Matter ◽

Cognitive Decline ◽

White Matter Hyperintensities ◽

White Matter Hyperintensity ◽

Subjective Cognitive Decline ◽

Age Related ◽

Lower Baseline ◽

Age Related Cognitive Decline ◽

Linear Regressions

Background: Previous research suggests that white matter hyperintensities, amyloid, and tau contribute to age-related cognitive decline. It remains unknown as to how these factors relate to one another and how they jointly contribute to cognitive decline in normal aging. This project examines the association between these pathologies and their relationship to cognitive decline. Methods: Cognitively normal older adult data from the Alzheimers Disease Neuroimaging Initiative were examined. Participants were included if they had no subjective cognitive decline, had baseline white matter hyperintensity, CSF AB42/40, CSF pTau181, and cognitive scores. Of the 102 participants included, only 79 had follow-up cognitive scores. Linear regressions examined the influence of white matter hyperintensities, amyloid, and tau on baseline and follow-up cognitive scores. Linear regressions also examined the association of amyloid and tau on white matter hyperintensities and between tau and amyloid. Results: Increased white matter hyperintensity load was associated with lower baseline memory (B= -0.20, p =.046), follow-up executive functioning (B= -0.32, p<.001), and follow-up ADAS-13 (B=2.69, p<.001) scores. White matter hyperintensities were not related to pTau or AB42/40. Lower AB42/40 was associated with increased pTau (p=.025). pTau was not associated with decline in any cognitive score. Lower AB42/40 was associated with lower baseline (p=.015) but not follow-up executive function. Discussion: White matter hyperintensities may be one of the earliest pathologies observed in healthy older adults that contribute to cognitive decline. The inclusion of white matter hyperintensities as an additional marker for early cognitive decline may improve our current understanding of age-related changes.

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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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The Association Between High-Molecular-Weight Adiponectin, Ghrelin and Leptin and Age-Related Cognitive Decline: Results From Longitudinal Aging Study Amsterdam

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa126 ◽

2020 ◽

Vol 76 (1) ◽

pp. 131-140

Author(s):

Merel van Andel ◽

Natasja M van Schoor ◽

Nicole C Korten ◽

Hannie C Comijs ◽

Annemieke C Heijboer ◽

...

Keyword(s):

Molecular Weight ◽

Cognitive Function ◽

Cognitive Decline ◽

Z Score ◽

Model Composite ◽

Hmw Adiponectin ◽

Age Related ◽

Adjusted Model ◽

Age Related Cognitive Decline

Abstract Background Age-related cognitive decline has large-scale functional and economic consequences and understanding its’ pathophysiological mechanisms is therefore essential. Previous research has suggested associations between hormones adiponectin, ghrelin and leptin and neurodegenerative disease. However, their association with age-related cognitive decline has not been fully described. We examine the association between serum high-molecular-weight (HMW) adiponectin, ghrelin and leptin and age-related cognitive decline in older adults. Methods The associations between HMW adiponectin, ghrelin and leptin and the Mini-Mental-State-Examination, Coding task (Coding), 15 Words Test (15WT) and composite Z-score (general cognitive function) were analyzed by means of a sex-stratified multivariable linear regression analysis in a population-based cohort of 898 older adults at baseline and after 3 years of follow-up. Results In women, we found a positive association between HMW adiponectin and general cognitive function at baseline (fully adjusted model composite Z-score standardized regression co-efficient beta [β] = .089, p = .025). After 3 years of follow-up, HMW adiponectin was associated with more decline in general cognitive function and information processing speed (fully adjusted model composite Z-score β = −.123, p = .018; Coding β = −.116, p = .027). Ghrelin and leptin were significantly associated with memory in a baseline subgroup analysis of older women. For men, we found no significant associations at baseline or follow-up. Conclusion Our results show variable associations between hormones HMW adiponectin, ghrelin and leptin and age-related cognitive decline in women but not in men. As there was no clear trend, all our results should be interpreted with caution.

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