Wennberg, Alexandra M V

Background: Transactive response DNA-binding protein of 43 kDa (TDP-43) is associated with hippocampal atrophy in Alzheimer’s disease (AD), but whether the association is modified by other factors is unknown. Objective: To evaluate whether the associations between TDP-43 and hippocampal volume and atrophy rate are affected by age, gender, apolipoprotein E ( APOE) ɛ4, Lewy bodies (LBs), amyloid-β (Aβ), or Braak neurofibrillary tangle (NFT) stage. Methods: In this longitudinal neuroimaging-clinicopathological study of 468 cases with AD neuropathological changes (Aβ-positive) that had completed antemortem head MRI, we investigated how age, gender, APOE ɛ4, presence of LBs, Aβ, TDP-43, and Braak NFT stages are associated with hippocampal volumes and rates of atrophy over time. We included field strength in the models since our cohort included 1.5T and 3T scans. We then determined whether the associations between hippocampal atrophy and TDP-43 are modified by these factors using mixed effects models. Results: Older age, female gender, APOE ɛ4, higher field strength, higher TDP-43, and Braak NFT stages were associated with smaller hippocampi. Rate of atrophy was greater with higher TDP-43 and Braak NFT stage, but lower in older patients. The association of TDP-43 with greater rate of atrophy was enhanced in APOE ɛ4 carriers ( p = 0.04). Conclusion: Neurodegenerative effects of TDP-43 seem to be independent of most factors except perhaps APOE in cases with AD neuropathological changes. TDP-43 and tau appear to behave independently of one another.

Introduction The reasons why women are at higher risk than men for developing dementia are unclear. Although studies implicate sex differences in the effect of stress on cognitive functioning, whether stressful life events are associated with subsequent cognitive decline has received scant research attention. Methods In Wave 3 (1993–1996) of the Baltimore Epidemiologic Catchment Area study, 337 men and 572 women (mean age = 47 years) reported recent (within the last year) and remote (from 1981 until 1 year ago) traumatic events (eg, combat) and stressful life events (eg, divorce/separation). At Waves 3 and 4 (2004–2005), they completed the Mini Mental State Examination (MMSE) and a word‐list memory test. Multivariable models were used to examine the association between traumatic and stressful life events at Wave 3 and cognitive change by Wave 4. Results A greater number of recent stressful life events at Wave 3, but not of more remote stressful events, was associated with greater verbal memory decline by Wave 4 in women but not in men. Stressful events were not associated with change in MMSE, and there were no associations between traumatic events occurring at any time and subsequent memory or MMSE decline in either sex. Conclusions Unlike men, middle‐aged women with a greater number of recent stressful life events demonstrate memory decline over a decade later. Sex differences in cognitive vulnerability to stressful life events may underlie women's increased risk of memory impairment in late life, suggesting that stress reduction interventions may help prevent cognitive decline in women.

ObjectivesTo determine the association of napping intention, frequency, and duration with cognition in a nationally‐representative sample of US older adults.MethodsWe performed a cross‐sectional analysis of community‐dwelling Medicare beneficiaries aged ≥65 years from Rounds 3 or 4 (2013‐2014) of the National Health and Aging Trends Study (N = 2549). Participants reported past‐month napping intention (intentional/unintentional), napping frequency (rarely/never [non‐nappers], some days [infrequent nappers], most days/every day [frequent nappers]), and average nap duration (we categorized as ≤30 minutes [short]; 31‐60 minutes [moderate]; and > 60 minutes [long]). Cognitive outcomes were performance on immediate and delayed word recall tests (IWR and DWR, respectively), the Clock Drawing Test (CDT), and self‐rated memory (score: 1[excellent]‐5[very poor]).ResultsAfter adjustment for potential confounders, unintentional nappers had poorer immediate word recall test performance than non‐nappers (B = −0.23, P < 0.01) and intentional nappers (B = −0.26, P < 0.01). After further adjustment for daytime sleepiness, frequent nappers reported poorer self‐rated memory than non‐nappers (B = 0.14, P < 0.05). Compared with short nappers, long nappers had poorer IWR (B = −0.26, P < 0.05) and CDT scores (B = −0.17, P < 0.05). Except for the association of nap duration with IWR and CDT, these associations remained after excluding participants with dementia and/or proxy respondents. Among participants undiagnosed with dementia or proxies, moderate‐duration naps were associated with better DWR than short naps (B = 0.24, P < 0.05). Neither napping intentionality nor frequency was associated with CDT performance.ConclusionsAmong older adults, distinct aspects of napping are associated with cognitive performance. Prospective research, with objective measures of napping, is needed to elucidate the link between napping and cognitive trajectories.

ObjectiveTo determine the cross‐sectional and longitudinal associations between diabetes treatment type and cognitive outcomes among type II diabetics.MethodsWe examined the association between metformin use, as compared to other diabetic treatment (ie, insulin, other oral medications, and diet/exercise) and cognitive test performance and mild cognitive impairment (MCI) diagnosis among 508 cognitively unimpaired at baseline type II diabetics enrolled in the Mayo Clinic Study of Aging. We created propensity scores to adjust for treatment effects. We used multivariate linear and logistic regression models to investigate the cross‐sectional association between treatment type and cognitive test z scores, respectively. Mixed effects models and competing risk regression models were used to determine the longitudinal association between treatment type and change in cognitive test z scores and risk of developing incident MCI.ResultsIn linear regression analyses adjusted for age, sex, education, body mass index, APOE ε4, insulin treatment, medical comorbidities, number of medications, duration of diabetes, and propensity score, we did not observe an association between metformin use and cognitive test performance. Additionally, we did not observe an association between metformin use and cognitive test performance over time (median = 3.7‐year follow‐up). Metformin was associated with an increased risk of MCI (subhazard ratio (SHR) = 2.75; 95% CI = 1.64, 4.63, P < .001). Similarly, other oral medications (SHR = 1.96; 95% CI = 1.19, 3.25; P = .009) and insulin (SHR = 3.17; 95% CI = 1.27, 7.92; P = .014) use were also associated with risk of MCI diagnosis.ConclusionsThese findings suggest that metformin use, as compared to management of diabetes with other treatments, is not associated with cognitive test performance. However, metformin was associated with incident MCI diagnosis.

Abstract Approximately half of older people report sleep disturbances, which are associated with various health conditions, including neurodegenerative disease and dementia. Indeed, 60 to 70% of people with cognitive impairment or dementia have sleep disturbances, which are linked to poorer disease prognosis. Sleep disturbances in people with dementia have long been recognized and studied; however, in the past 10 years, researchers have begun to study disturbed sleep, including sleep fragmentation, abnormal sleep duration, and sleep disorders, as risk factors for dementia. In this review the authors summarize evidence linking sleep disturbance and dementia. They describe how specific aspects of sleep (e.g., quality, duration) and the prevalence of clinical sleep disorders (e.g., sleep-disordered breathing, rapid eye movement sleep behavior disorder) change with age; how sleep parameters and sleep disorders are associated with the risk of dementia; how sleep can be disturbed in dementia; and how disturbed sleep affects dementia prognosis. These findings highlight the potential importance of identifying and treating sleep problems and disorders in middle-aged and older adults as a strategy to prevent cognitive decline and dementia. The authors also review recent evidence linking sleep disturbances to the pathophysiology underlying dementing conditions, and briefly summarize available treatments for sleep disorders in people with dementia.

AbstractIntroductionFamily history (FH) of Alzheimer's disease (AD) affects mitochondrial function and may modulate effects of translocase of the outer mitochondrial membrane 40 kDa (TOMM40) rs10524523 ('523) poly‐T length on memory decline.MethodsFor 912 nonapolipoprotein ε4 middle‐aged adults and 365 aged adults across the AD spectrum, linear mixed models gauged FH and TOMM40 '523 interactions on memory and global cognition between baseline and up to 10 years later. A cerebrospinal fluid mitochondrial function biomarker was also assessed.ResultsFor FH negative participants, gene‐dose preservation of memory and global cognition was seen for “very long” versus “short” carriers. For FH positive, an opposite gene‐dose decline was seen for very long versus short carriers. Maternal FH was a stronger predictor in aged, but not middle‐aged, participants. Similar gene‐dose effects were seen for the mitochondrial biomarker aspartate aminotransferase.DiscussionThese results may clarify conflicting findings on TOMM40 poly‐T length and AD‐related decline.