Cognitive Reserve and Mild Cognitive Impairment

Background and Objectives Little is known about the effect of education or other indicators of cognitive reserve on the rate of reversion from mild cognitive impairment (MCI) to normal cognition (NC) or the relative rate (RR) of reversion from MCI to NC vs progression from MCI to dementia. Our objectives were to (1) estimate transition rates from MCI to NC and dementia and (2) determine the effect of age, APOE, and indicators of cognitive reserve on the RR of reversion vs progression using multistate Markov modeling. Methods We estimated instantaneous transition rates between NC, MCI, and dementia after accounting for transition to death across up to 12 assessments in the Nun Study, a cohort study of religious sisters aged 75+ years. We estimated RRs of reversion vs progression for age, APOE, and potential cognitive reserve indicators: education, academic performance (high school grades), and written language skills (idea density, grammatical complexity). Results Of the 619 participants, 472 were assessed with MCI during the study period. Of these 472, 143 (30.3%) experienced at least one reverse transition to NC, and 120 of the 143 (83.9%) never developed dementia (mean follow-up = 8.6 years). In models adjusted for age group and APOE, higher levels of education more than doubled the RR ratio of reversion vs progression. Novel cognitive reserve indicators were significantly associated with a higher adjusted RR of reversion vs progression (higher vs lower levels for English grades: RR ratio = 1.83; idea density: RR ratio = 3.93; and grammatical complexity: RR ratio = 5.78). Discussion Knowledge of frequent reversion from MCI to NC may alleviate concerns of inevitable cognitive decline in those with MCI. Identification of characteristics predicting the rate of reversion from MCI to NC vs progression from MCI to dementia may guide population-level interventions targeting these characteristics to prevent or postpone MCI and dementia. Research on cognitive trajectories would benefit from incorporating predictors of reverse transitions and competing events, such as death, into statistical modeling. These results may inform the design and interpretation of MCI clinical trials, given that a substantial proportion of participants may experience improvement without intervention

Diabetes Is Associated with Cerebrovascular but not Alzheimer\u27s Disease Neuropathology

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood. METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of \u3e1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression. RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P \u3c .0001), specifically lacunes (OR = 1.71, P \u3c .0001), but not Alzheimer\u27s disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer\u27s neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone. DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer\u27s disease pathology, and at least some of diabetes\u27 relationship to cognitive impairment may be modified by neuropathology

Effects of ignoring baseline on modeling transitions from intact cognition to dementia

This paper evaluates the effect of ignoring baseline when modeling transitions from intact cognition to dementia with mild cognitive impairment (MCI) and global impairment (GI) as intervening cognitive states. Transitions among states are modeled by a discrete-time Markov chain having three transient (intact cognition, MCI, and GI) and two competing absorbing states (death and dementia). Transition probabilities depend on two covariates, age and the presence/absence of an apolipoprotein E-[epsilon]4 allele, through a multinomial logistic model with shared random effects. Results are illustrated with an application to the Nun Study, a cohort of 678 participants 75+ years of age at baseline and followed longitudinally with up to ten cognitive assessments per nun.

Healthy ageing in the Nun Study: Definition and neuropathologic correlates

Abstract Background: although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined. Objective: to develop a definition of healthy ageing and investigate its association with longevity and neuropathology. Methods: analyses were based on cognitive, physical, and post-mortem assessments from 1991 to 1998 in the Nun Study, a longitudinal study of ageing in participants 75+ years at baseline. We defined three mutually exclusive levels of healthy ageing (excellent, very good, and good) based on measures of global cognitive function, short-term memory, basic and instrumental activities of daily living, and self-rated function. Mortality analyses were based on 636 participants; neuropathologic analyses were restricted to 221 who had died and were autopsied. Results: only 11% of those meeting criteria for the excellent level of healthy ageing at baseline subsequently died, compared with 24% for the very good, 39% for the good, and 60% for the remaining participants. Survival curves showed significantly greater longevity with higher levels of healthy ageing. The risk of not attaining healthy ageing, adjusted for age, increased two-fold in participants with brain infarcts alone, six-fold in those with Alzheimer neuropathology alone, and more than thirteen-fold in those with both brain infarcts and Alzheimer neuropathology. Conclusions: the biological validity of our definition of healthy ageing is supported by its strong association with mortality and longevity. Avoiding Alzheimer and stroke neuropathology is critical to the maintenance of healthy ageing, and the presence of both pathologies dramatically decreases the likelihood of healthy ageing

Functional social support and cognitive function in middle- and older-aged adults: a systematic review of cross-sectional and cohort studies

Abstract Background Intact cognitive function is crucial for healthy aging. Functional social support is thought to protect against cognitive decline. We conducted a systematic review to investigate the association between functional social support and cognitive function in middle- and older-aged adults. Methods Articles were obtained from PubMed, PsycINFO, Sociological Abstracts, CINAHL, and Scopus. Eligible articles considered any form of functional social support and cognitive outcome. We narratively synthesized extracted data by following the Synthesis Without Meta-Analysis (SWiM) guidelines and assessed risk of bias using the Newcastle–Ottawa Scale (NOS). Results Eighty-five articles with mostly low risk-of-bias were included in the review. In general, functional social support—particularly overall and emotional support—was associated with higher cognitive function in middle- and older-aged adults. However, these associations were not all statistically significant. Substantial heterogeneity existed in the types of exposures and outcomes evaluated in the articles, as well as in the specific tools used to measure exposures and outcomes. Conclusions Our review highlights the role of functional social support in the preservation of healthy cognition in aging populations. This finding underscores the importance of maintaining substantive social connections in middle and later life. Systematic review registration Rutter EC, Tyas SL, Maxwell CJ, Law J, O'Connell ME, Konnert CA, Oremus M. Association between functional social support and cognitive function in middle-aged and older adults: a protocol for a systematic review. BMJ Open;10(4):e037301. https://doi.org/10.1136/bmjopen-2020-03730