Haplogroups of Mitochondrial DNA Differentiate Patterns of Cognitive Change Over 7 Years

Abstract Mitochondrial DNA (mtDNA) may play an important role in Alzheimer’s disease (AD) and cognitive decline. A particular haplogroup of mtDNA (haplogroup J), has been observed more commonly in patients with AD than in cognitively normal controls. We used mtDNA haplogroups to predict change in cognitive performance over seven years. We hypothesized that haplogroup J would predict poorer cognitive function and steeper cognitive decline. We analyzed data from 140 cognitively normal older adults (age 65+) who participated in the University of Kansas Alzheimer’s Disease Center annual registry. We used factor analysis to create three composite scores (verbal memory, attention, executive function) from 11 individual cognitive tests. We performed latent growth curve modeling to describe trajectories of cognitive performance and change. We compared haplogroup H, the most common, to haplogroup J, the potential risk group. Results indicated haplogroup J carriers had significantly lower baseline performance (B=-.049, p< .01) and slower rates of improvement (B=-.046, p < .05) on tests of verbal memory compared to haplogroup H. For executive function, groups did not differ at baseline (B=.065, p>.10), but haplogroup J had slower rates of improvement (B=-.097, p < .01). There were no differences in attention across groups in performance (B=.135, p>.10) or change (B=-.01, p>.10). Our results reinforce the important role of mtDNA in changes to cognitive function with aging and imply that the effects of haplogroup J may vary across cognitive domains. Future research should investigate the mechanisms by which mtDNA might affect performance on specific cognitive domains across haplogroups.

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Daily social interactions related to daily performance on mobile cognitive tests among older adults

PLoS ONE ◽

10.1371/journal.pone.0256583 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0256583

Author(s):

Ruixue Zhaoyang ◽

Stacey B. Scott ◽

Lynn M. Martire ◽

Martin J. Sliwinski

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Cognitive Decline ◽

Social Interactions ◽

Cognitive Performance ◽

Behavioral Interventions ◽

Daily Life ◽

Cognitive Tests

The lack of social contact or good social relationships has been linked with cognitive decline and higher risk for Alzheimer’s disease and related dementias. One important but unexamined question is how daily social interactions relate to older adults’ cognitive function in daily life. The present study examined how changes in daily social interactions related to fluctuations in older adults’ performance on mobile cognitive tests from day to day. Using an ecological momentary assessments approach, 312 older adults (aged 70 to 90 years) completed surveys on social interactions and mobile cognitive tests five times a day for 16 consecutive days using smartphones. Multilevel modeling was used for analyses. Results demonstrated that having more daily social interactions, especially more pleasant social interactions, related to better cognitive performance the same day and over the subsequent two days. Cognitive performance, however, did not predict subsequent changes in social interactions across days. At the between-person level, older adults who had more (vs. less) frequent interactions with close partners on average, especially with their friends, had better cognitive performance. Finally, the average levels of social interactions also moderated the within-person associations between daily social interactions and the same-day cognitive performance. In sum, results from this study highlight the importance of having pleasant social interactions and frequent interactions with friends for older adults’ cognitive function in daily life, and have important implications for future behavioral interventions targeting certain features of daily social interactions to reduce risk of cognitive decline and Alzheimer’s disease and related dementias.

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Association of Sleep Disturbances and Cognitive Decline among Cognitively Normal Elders Over Time

10.21203/rs.3.rs-416599/v1 ◽

2021 ◽

Author(s):

Wei Feng ◽

Mandela William Nzoyoum Kuetche ◽

Meng Zhang ◽

MengMeng Liu ◽

Deginet Aklilu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Cognitive Decline ◽

Regression Models ◽

Sleep Disturbances ◽

Amyloid Pet ◽

Longitudinal Impact ◽

Cognitively Normal ◽

Over Time

Abstract Background: While sleep disturbances (SD) has been shown to be associated with worse cognition, but the causal relationship between the two subjects to debate. Our objective was to investigate the longitudinal impact of SD on cognitive function.Objective: To determine the effect of self-reported clinical diagnosis of SD on longitudinal changes in brain amyloid-PET, CSF-biomarkers (Aβ42, T-tau and P-tau) and cognitive function in cognitively normal.Methods: A total of 463 cognitively normal elders (357 normal and 106 SD) were included. Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants were collected from 2005 to 2020. The generalized linear mixed models adjusting variables which were selected by the Akaike Information Criterion (AIC) and the marginal effect estimation method was used to estimate the risk effect of SD. Cox proportional hazards regression models estimated the relative hazard of Alzheimer’s Disease (AD), among baseline SD patients.Results: The age range of participants was 73.60±5.71 years old, and the female proportion was 43.63%. In adjusted regression models, Participants with baseline SD had higher likelihood of developing worse cognition over subsequent follow-up, PACC (decrease 7.53 points [95%CI, 7.36-7.70]; P<0.001), MMSE (decrease 5.26 points [95%CI, 5.17-5.35]; P<0.001), and CDR–Sum of Boxes (increase 5.61 points [95%CI, 5.67-5.54]; P=0.001). Similarly, Cox regression analysis suggested that sleep disturbances is a risk factor of AD (HR=1.55, 95% CI=1.08 to 2.22).Conclusion: SD probably is a warning sign of AD, because it is associated with greater likelihood of cognitive decline or dementia over time. Associations are likely multifactorial and could be explained by intervening variables in the path from SD to dementia, or by common risk factors for pathological processes in brain. These findings suggest need for more attentions of older adults with sleep compromise.

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Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

Journal of the International Neuropsychological Society ◽

10.1017/s1355617721000801 ◽

2021 ◽

pp. 1-9

Author(s):

Jairo E. Martinez ◽

Enmanuelle Pardilla-Delgado ◽

Edmarie Guzmán-Vélez ◽

Clara Vila-Castelar ◽

Rebecca Amariglio ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sex Differences ◽

Cognitive Decline ◽

Verbal Memory ◽

Autosomal Dominant ◽

Memory Performance ◽

Subjective Cognitive Decline ◽

Mutation Carriers ◽

Study Partner

Abstract Objective: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance. Methods: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Results: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Conclusions: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

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SUBJECTIVE COGNITIVE DECLINE, LONGITUDINAL COGNITIVE PERFORMANCE, AND IMAGING BIOMARKERS IN PRECLINICAL ALZHEIMER’S DISEASE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.020 ◽

2017 ◽

Vol 13 (7) ◽

pp. P176

Author(s):

Rebecca Amariglio ◽

Rachel F. Buckley ◽

Beth C. Mormino ◽

Cathy Wang ◽

Sarah L. Aghjayan ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Cognitive Performance ◽

Imaging Biomarkers ◽

Subjective Cognitive Decline ◽

Preclinical Alzheimer’S Disease

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Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

Journal of Alzheimer s Disease ◽

10.3233/jad-210333 ◽

2021 ◽

pp. 1-11

Author(s):

Fennie Choy Chin Wong ◽

Seyed Ehsan Saffari ◽

Chathuri Yatawara ◽

Kok Pin Ng ◽

Nagaendran Kandiah ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Executive Function ◽

White Matter ◽

White Matter Hyperintensities ◽

Small Vessel Disease ◽

Amyloid Β ◽

Intracranial Volume ◽

Linear Regression Models ◽

Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

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Moderating Effect of Insulin Resistance on the Relationship between Gray Matter Volumes and Cognitive Function

Journal of Clinical Medicine ◽

10.3390/jcm7110413 ◽

2018 ◽

Vol 7 (11) ◽

pp. 413 ◽

Cited By ~ 2

Author(s):

Jiyeon Lee ◽

Jihyeon Kim ◽

Seong Shin ◽

Soowon Park ◽

Dong Yoon ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Insulin Resistance ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Cognitive Decline ◽

Gray Matter ◽

Structural Changes ◽

Gray Matter Volume ◽

Volume Loss ◽

Matter Volume

Background: It is controversial whether exposure to insulin resistance accelerates cognitive deterioration. The present study aimed to investigate the association between insulin resistance and gray matter volume loss to predict the cognitive decline. Methods: We recruited 160 participants (78 with Alzheimer’s disease and 82 without Alzheimer’s disease). Insulin resistance, regional gray matter volume, and cognitive function were assessed. A hierarchical moderated multiple regression (MMR) model was used to determine any associations among insulin resistance, structural changes in the brain, and cognitive decline. Results: The volumes of 7 regions in the gray matter were negatively related to insulin resistance in Alzheimer’s disease (p =0.032). Hierarchical MMR analysis indicated that insulin resistance did not directly affect the cognitive decline but moderated the cognitive decline through the decrease in gray matter volume in the key brain regions, i.e., inferior orbitofrontal gyrus (left), middle cingulate gyrus (right), hippocampus (right), and precuneus (right) (p < 0.05 in each case). Conclusion: Insulin resistance appears to exacerbate the cognitive decline associated with several gray matter volume loss.

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