Exploring the differential impacts of social isolation, loneliness, and their combination on the memory of an aging population: A 6-year longitudinal study of the CLSA.

Memory plays a crucial role in cognitive health. Social isolation (SI) and loneliness (LON) are recognized risk factors for global cognition, although their combined effects on memory have been understudied in the literature. This study used three waves of data over six years from the Canadian Longitudinal Study on Aging to examine whether SI and LON are individually and jointly associated with memory in community-dwelling middle-aged and older adults (n = 14,208). LON was assessed with the question: "In the last week, how often did you feel lonely?". SI was measured using an index based on marital/cohabiting status, retirement status, social activity participation, and social network contacts. Memory was evaluated with combined z-scores from two administrations of the Rey Auditory Verbal Learning Test (immediate-recall, delayed-recall). We conducted our analyses using all available data across the three timepoints and retained participants with missing covariate data. Linear mixed models were used to regress combined memory scores onto SI and LON, adjusting for sociodemographic, health, functional ability, and lifestyle variables. Experiencing both SI and LON had the greatest inverse effect on memory (least-squares mean: -0.80 [95 % confidence-interval: -1.22, -0.39]), followed by LON alone (-0.73 [-1.13, -0.34]), then SI alone (-0.69 [-1.09, -0.29]), and lastly by being neither lonely nor isolated (-0.65 [-1.05, -0.25]). Sensitivity analyses confirmed this hierarchy of effects. Policies developed to enhance memory in middle-aged and older adults might achieve greater benefits when targeting the alleviation of both SI and LON rather than one or the other individually.

The association between memory, COVID-19 testing, and COVID-19 incidence in middle-aged and older adults: a prospective analysis of the CLSA.

We investigated the association between pre-COVID-19 memory function and (a) receipt of a COVID-19 test and (b) incidence of COVID-19 using the COVID-19 Questionnaire Study (CQS) of the Canadian Longitudinal Study on Aging (CLSA). The CQS included 28,565 middle-aged and older adults. We regressed receipt of a COVID-19 test on participants' immediate and delayed recall memory scores and re-ran the regression models with COVID-19 incidence as the outcome. All regression models were adjusted for sociodemographic, lifestyle, and health covariates. In the analytical sample (n = 21,930), higher delayed recall memory (better memory) was significantly associated with lower COVID-19 incidence. However, this association was not significant for immediate recall memory. Immediate and delayed recall memory were not associated with receipt of a COVID-19 test. Health policymakers and practitioners may viewmemory status as a potential risk for COVID-19. Memory status may not be a barrier to COVID-19 testing.

Insulin Use in Type 2 Diabetes and the Risk of Dementia: A Comparative Population-Based Cohort Study.

OBJECTIVE: Evidence of an increased dementia risk with insulin use in type 2 diabetes is weakened by confounding by indication and disease severity. Herein we reassess this association, while accounting for confounding through design and analysis. RESEARCH DESIGN AND METHODS: Using administrative health care data from British Columbia, Canada, we identified patients diagnosed with type 2 diabetes in 1998-2016. To adjust for confounding by diabetes severity through design, we compared new users of insulin to new users of a noninsulin class, both from a restricted cohort of those who previously received two noninsulin antihyperglycemic classes. We further adjusted for confounding using 1) conventional multivariable adjustment and 2) inverse probability of treatment weighting (IPTW) based on the high-dimensional propensity score algorithm. The hazard ratio [HR] (95% CI) of dementia was estimated using cause-specific hazards models with death as a competing risk. RESULTS: The analytical comparative cohort included 7,863 insulin versus 25,230 noninsulin users. At baseline, insulin users were more likely to have worse health indicators. A total of 78 dementia events occurred over a median (interquartile range) follow-up of 3.9 (5.9) years among insulin users, and 179 events occurred over 4.6 (4.4) years among noninsulin users. The HR (95% CI) of dementia for insulin use versus noninsulin use was 1.68 (1.29-2.20) before adjustment and 1.39 (1.05-1.86) after multivariable adjustment, which was further attenuated to 1.14 (0.81-1.60) after IPTW. CONCLUSIONS: Among individuals with type 2 diabetes previously exposed to two noninsulin antihyperglycemic medications, no significant association was observed between insulin use and all-cause dementia.

Functional social isolation mediates the association between depression and executive function in older women: findings from the Canadian Longitudinal Study on Aging Comprehensive cohort.

Depression and social isolation increase risk for executive function declines and are among the top five modifiable risk factors for dementia. However, the interrelationships between depression, social isolation and executive function are not well established. Further evidence is needed to inform strategies to promote executive function and independence in older age. We examined whether social isolation mediated the association between depression and executive function in community-dwelling middle-aged and older adults and whether this association was modified by age and sex. Adults aged 45 to 85 years from the Canadian Longitudinal Study on Aging (CLSA) Comprehensive cohort were followed over three years (complete case analysis, n = 14,133). Baseline depressive symptoms, a history of clinical depression, and functional social isolation (perceived lack of social support) were self-reported. Executive function at follow-up was a composite measure of five cognitive tests. Conditional process analysis assessed the mediating effects of functional social isolation across age group and sex, adjusted for sociodemographic and health covariates. Functional social isolation significantly mediated the association of depressive symptoms (proportion mediated [PM] = 8.0%) or clinical depression (PM = 17.5%) with executive function only among women aged 75+ years. Functional social isolation explains a proportion of the total effect of depressive symptoms or clinical depression on executive function in women aged 75 and older. Although reverse causation cannot be ruled out, our findings suggest that interventions that reduce functional social isolation or depression in older women may promote executive function.

The Association Between Emotional Expressivity in Autobiographies from Early Adulthood and the Risk of Dementia in the Context of Written Language Skills.

Background: Risk factors for dementia, such as Alzheimer's disease, are complex and span a lifetime. Exploring novel factors, such as characteristics of writing, may provide insight into dementia risk. Objective: To investigate the association between emotional expressivity and risk of dementia in the context of a previously identified risk factor, written language skills. Methods: The Nun Study recruited 678 religious sisters aged 75 + years. Of these, 149 U.S.-born participants had archived autobiographies handwritten at a mean age of 22 years. The autobiographies were scored for frequency of emotion word usage and language skills (e.g., idea density). The association of emotional expressivity and a four-level composite variable (combining high/low emotional expressivity and high/low idea density) with dementia was assessed using logistic regression models adjusted for age, education, and apolipoprotein E. Results: Within the composite variable, odds of dementia increased incrementally, with opposing effects of emotional expressivity across the two idea density levels. Compared to the referent category (low emotional expressivity/high idea density), the risk of dementia increased in those with high emotional expressivity/high idea density (OR = 2.73, 95% CI = 1.05-7.08), while those with low emotional expressivity/low idea density had the highest risk (OR = 18.58, 95% CI = 4.01-86.09). Conclusion: Dementia risk is better captured by inclusion of multiple measures relating to characteristics of writing. Emotional expressivity may be protective when individuals are at increased risk due to poor written language skills (i.e., low idea density), but detrimental when not at risk (i.e., high idea density). Our findings indicate that emotional expressivity is a contextually-dependent novel risk factor for dementia.

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

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-2020-037301.

The association between functional social support and memory in middle-aged and older adults: A Prospective Analysis of the Canadian Longitudinal Study on Aging's Comprehensive Cohort.

BACKGROUND: Functional social support (FSS) impacts memory function through biological and psychological pathways. In a national sample of middle-aged and older adults in Canada, we explored the association between FSS and changes in memory over three years and investigated effect modification by age group and sex. METHODS: We analyzed data from the Comprehensive Cohort of the Canadian Longitudinal Study on Aging (CLSA). FSS was measured with the Medical Outcomes Study - Social Support Survey; memory was measured with combined z-scores from immediate and delayed recall administrations of a modified version of the Rey Auditory Verbal Learning Test. We regressed memory change scores over three years on baseline overall FSS and four FSS subtypes in separate multiple linear regression models, controlling for sociodemographic, health, and lifestyle covariates. We also stratified our models by age group and sex. RESULT: We found positive associations between higher FSS and improvement in memory score, although only the tangible FSS subtype (availability of practical assistance) was significantly associated with changes in memory (ß^ = 0.07; 95% confidence interval = 0.01, 0.14). After stratification by age group and sex, this association remained significant for males, although we found no evidence of effect modification. CONCLUSION: In a cognitively healthy sample of middle-aged and older adults, we found a statistically significant and positive association between tangible FSS and memory change over three years of follow-up. We did not find adults with low FSS to be at increased risk of memory decline compared to adults with higher FSS.

Subtypes of social support availability are not differentially associated with memory: a cross-sectional analysis of the Comprehensive Cohort of the Canadian Longitudinal Study on Aging.

This study investigated the association between subtypes of social support availability (SSA) and memory in persons aged 45 to 85 years (n = 24,719). We examined two memory outcomes using a modified Rey Auditory Verbal Learning Test (RAVLT)-immediate recall (RAVLT I) and delayed recall (RAVLT II)-and five subtypes of SSA: affectionate, emotional/informational, positive interactions, tangible, overall. We found statistically significant and adjusted positive associations between all SSA subtypes and memory, except for positive interactions and delayed recall memory. For RAVLT I, the regression coefficients (߈s) ranged from 0.03 to 0.07; the ߈s for RAVLT II ranged from 0.02 to 0.05. The differences in ߈s for each SSA subtype (߈ RAVLT I - ߈ RAVLT II) ranged from 0.00 to 0.02 (mean difference = 0.01; 95% confidence interval = -0.01 to 0.03). All effect sizes, regardless of SSA subtype or memory outcome, were small and clinically unimportant.

Associations of Mid- and Late-Life Severe Hypoglycemic Episodes With Incident Dementia Among Patients With Type 2 Diabetes: A Population-Based Cohort Study.

OBJECTIVE: Severe hypoglycemia is associated with an increased risk of dementia. We examined if the association is consistently present in mid- and late-life hypoglycemia. RESEARCH DESIGN AND METHODS: Using health care data from Population Data BC, we created a base cohort of patients age ≥40 years with incident type 2 diabetes. Exposure was the first occurrence of severe hypoglycemia (hospitalization or physician visit). We assessed exposure versus no exposure in mid- (age 45-64 years) and late-life (age 65-84 years) cohorts. Index date was the later of the 45th birthday (midlife cohort), 65th birthday (late-life cohort), or diabetes diagnosis. Those with hypoglycemia or dementia before the index date were excluded. Patients were followed from index date until dementia diagnosis, death, emigration, or 31 December 2018. Exposure was modeled as time dependent. We adjusted for confounding using propensity score weighting. Dementia risk was estimated using cause-specific hazards models with death as a competing risk. RESULTS: Of 221,683 patients in the midlife cohort, 1,793 experienced their first severe hypoglycemic event. Over a median of 9.14 years, 3,117 dementia outcomes occurred (32 among exposed). Of 223,940 patients in the late-life cohort, 2,466 experienced their first severe hypoglycemic event. Over a median of 6.7 years, 15,997 dementia outcomes occurred (158 among exposed). The rate of dementia was higher for those with (vs. without) hypoglycemia in both the mid- (hazard ratio 2.85; 95% CI 1.72-4.72) and late-life (2.38; 1.83-3.11) cohorts. CONCLUSIONS: Both mid- and late-life hypoglycemia were associated with approximately double the risk of dementia, indicating the need for prevention throughout the life course of those with diabetes.

Hypoglycaemia and the risk of dementia: a population-based cohort study using exposure density sampling.

BACKGROUND: Previous studies have shown hypoglycaemia to be associated with an increased risk of dementia; however, there are several design challenges to consider. The objective of this study is to assess the association between hypoglycaemia and dementia while addressing these challenges using a lag period, exposure density sampling (EDS) and inverse probability of treatment weighting (IPTW). METHODS: This was a population-based cohort using data (1996-2018) from British Columbia, Canada. From a cohort of incident type 2 diabetes patients aged 40-70 years, we created a dynamic sub-cohort of hypoglycaemia-exposed (≥1 episode requiring hospitalization or a physician visit) and unexposed individuals using EDS, in which four unexposed individuals per one exposed were randomly selected into risk sets based on diabetes duration and age. Follow-up was until dementia diagnosis, death, emigration or 31 December 2018. Those diagnosed with dementia within 2 years of follow-up were censored. We adjusted for confounding using IPTW and estimated the hazard ratio (HR, 95% CI) of dementia using weighted conditional cause-specific hazards risk models with death as a competing risk. RESULTS: Among 13 970 patients with incident type 2 diabetes, 2794 experienced hypoglycaemia. There were 329 dementia events over a median (interquartile range: IQR) follow-up of 5.03 (5.7) years. IPTW resulted in well-balanced groups with weighted incidence rates (95% CI) of 4.59 (3.52, 5.98)/1000 person-years among exposed and 3.33 (2.58, 3.88)/1000 person-years among unexposed participants. The risk of dementia was higher among those with hypoglycaemia (HR, 1.83; 95% CI 1.31, 2.57). CONCLUSIONS: After addressing several methodological challenges, we showed that hypoglycaemia contributes to an increased risk of all-cause dementia among patients with type 2 diabetes.

Urban-rural variation in the association between social support availability and cognitive function in middle-aged and older adults: Results from the baseline Tracking Cohort of the Canadian Longitudinal Study on Aging.

The purpose of this study was to investigate if and how the associations between social support availability (SSA) and cognitive function varied across urban, rural, and geographical regions in Canada. Data from a population-level sample of community-dwelling adults aged 45-85 years were obtained from the baseline Tracking Cohort of the Canadian Longitudinal Study on Aging. The associations between SSA and two domains of cognitive function, memory and executive function, were analyzed using multilevel regression models. SSA was positively and significantly associated with both executive function and memory. We found SSA had stronger positive associations with executive function among participants living in rural areas compared to urban areas in all geographical regions; however, geographical variation in the associations between SSA and memory were not supported by model results. Understanding how the associations between cognitive function and modifiable risk factors, including SSA, vary across geographical contexts is important for developing policies and programs to support healthy aging.

Cognitive Reserve and Mild Cognitive Impairment: Predictors and Rates of Reversion to Intact Cognition vs Progression to Dementia.

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.

Augmented likelihood for incorporating auxiliary information into left-truncated data.

Time-to-event data are often subject to left-truncation. Lack of consideration of the sampling condition will introduce bias and loss in efficiency of the estimation. While auxiliary information from the same or similar cohorts may be available, challenges arise due to the practical issue of accessibility of individual-level data and taking account of various sampling conditions for different cohorts. In this paper, we introduce a likelihood-based method to incorporate information from auxiliary data to eliminate the left-truncation problem and improve efficiency. A one-step Monte-Carlo Expectation-Maximization algorithm is developed to calculate an augmented likelihood through creating pseudo-data sets which extend the form and conditions of the observed sample. The method is illustrated by both a real dataset and simulation studies.

Multimorbidity in Canadians living in the community: Results from the Canadian Longitudinal Study of Aging.

OBJECTIVE: To determine the mean number of chronic diseases in Canadians aged 45 to 85 years who are living in the community, and to characterize the association of multimorbidity with age, sex, and social position. DESIGN: An analysis of data from the Canadian Longitudinal Study on Aging. The number of self-reported chronic diseases was summed, and then the mean number of chronic health problems was standardized to the 2011 Canadian population. Analyses were conducted stratified on sex, age, individual income, household income, and education level. SETTING: Canada. PARTICIPANTS: A total of 21 241 community-living Canadians aged 45 to 85 years. MAIN OUTCOME MEASURES: Overall, 31 chronic diseases (self-reported from a list) were considered, as were risk factors that were not mental health conditions or acute in nature. Age, sex, education, and household and individual incomes were also self-reported. RESULTS: Multimorbidity was common, and the mean number of chronic illnesses was 3.1. Women had a higher number of chronic illnesses than men. Those with lower income and less education had more chronic conditions. The number of chronic conditions was strongly associated with age. The mean number of conditions was 2.1 in those aged 45 to 54; 2.9 in those 55 to 64; 3.8 in those aged 65 to 74, and 4.8 in those aged 75 and older (P < .05, ANOVA [analysis of variance]). CONCLUSION: Multimorbidity is common in the Canadian population and is strongly related to age.

Association between functional social support and cognitive function in middle-aged and older adults: a protocol for a systematic review.

INTRODUCTION: Maintenance of cognitive function into old age is important for ageing populations. Researchers seek to identify modifiable risk and protective factors for cognitive function. One such modifiable factor is functional social support, that is, one's perception of whether their social network can provide resources such as material help, companionship, information and emotional contact, if needed. While the literature generally reports positive associations between functional social support and cognitive function, results vary according to study methods such as the tool used to measure functional social support or the specific cognitive domain under investigation. Our review will summarise the association between functional social support and cognitive function in middle-aged and older-aged adults who reside in any setting (eg, community dwelling, long-term care facilities). We will also identify sources of discrepant findings between studies. METHODS AND ANALYSIS: This protocol was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guideline. PubMed, PsycINFO, Sociological Abstracts, Cumulative Index of Nursing and Allied Health Literature (CINAHL) and Scopus will be searched from inception to the present using a search strategy developed with a medical librarian's help. We will supplement the database searches with a grey literature search. English-language or French-language studies with a comparison group will be subject to inclusion, regardless of the measures used to assess functional social support or cognitive function. We will assess risk of bias with the Cochrane Risk of Bias Tool-Version 2 or the Newcastle-Ottawa Scale, narratively synthesise the extracted data and conduct a meta-analysis of studies with similar characteristics (eg, sample age and sex, cognitive function outcomes). Two independent raters will screen articles and assess risk of bias. ETHICS AND DISSEMINATION: This review is timely given the push toward early diagnosis and treatment of dementia/major neurocognitive disorder and other types of cognitive impairment. This protocol does not require a formal ethics review. We will publish our findings in a peer-reviewed journal.

Carotid pulse pressure and intima media thickness are independently associated with cerebral hemodynamic pulsatility in community-living older adults.

Vascular aging is associated with markers of cerebrovascular impairment. Whether discrete characteristics of arterial structure and function have independent and/or additive effects on cerebral hemodynamics, however, is not completely understood. We examined the association of cerebral hemodynamics with common carotid artery intima-media thickness (IMT) and pulse pressure (PP) in 61 older adults with prevalent cardiometabolic risk but no history of cerebrovascular disease. We calculated pulsatility index (PI) and hypercapnic reactivity of the middle cerebral artery, as well as global blood flow through the extracranial arteries. The dominant effects were related to hemodynamic pulsatility. In adults with metabolic syndrome, PI was related to IMT (r = 0.48, P = 0.003) after adjustment for age and sex. Without metabolic syndrome, PI was directly related to PP (r = 0.63, P = 0.003). Across the whole cohort, PP [ß (95%CI) = 0.42 (0.18, 0.67), P = 0.001] and IMT [0.42 (0.18, 0.67), P < 0.001] remained significant predictors of PI, after accounting for individual cardiometabolic risk factors. The independent and combined effects of IMT and PP were tested by binarizing PP and IMT at the sample median. Participants with both IMT and PP above their respective medians had elevated PI compared with those with both vascular markers below the median [median (interquartile range) = 1.06 (0.22) vs. 0.84 (0.14), P = 0.003)]. PI was not different from the low risk group if only one of IMT or PP were above the median. Although overall vascular burden was low, moderate associations with PI persisted, suggesting pulsatile characteristics represent one of the earliest markers linking vascular aging to changes in brain health.

Social support availability is positively associated with memory in persons aged 45-85 years: A cross-sectional analysis of the Canadian Longitudinal Study on Aging.

OBJECTIVES: This study examines the association between a modifiable psychosocial factor, social support availability (SSA), and the memory domain of cognitive function in persons aged 45-85 years. METHODS: We used baseline data from the Canadian Longitudinal Study on Aging (CLSA) (n = 21,241) to conduct multiple linear regression analyses of the association between SSA (overall and four subscales) and memory. The CLSA assessed immediate and delayed recall memory using the Rey Auditory Verbal Learning Test (RAVLT). RESULTS: Higher levels of each type of SSA were positively associated with better performance on both immediate and delayed recall memory. The largest associations (ß coefficients [95% confidence intervals]) for z-score differences on the RAVLT were observed for overall SSA (immediate: 0.07 [0.04-0.10]; delayed recall: 0.06 [0.02-0.09]) and the emotional/informational subscale (immediate: 0.06 [0.03-0.09]; delayed recall: 0.05 [0.02-0.08]). CONCLUSION: SSA is modifiable and positively associated with memory. Public health initiatives to provide support resources such as material aid, emotional support, or companionship may entail positive benefits for memory. Promotion of SSA is also important for policies encouraging early diagnosis and intervention in dementia.

Migraine and the risk of all-cause dementia, Alzheimer's disease, and vascular dementia: A prospective cohort study in community-dwelling older adults.

OBJECTIVES: Dementia is the most common neurological disease in older adults; headaches, including migraines, are the most common neurological disorder across all ages. The objective of this study was to explore the relationship between migraines and dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). METHODS: Analyses were based on 679 community-dwelling participants 65+ years from the Manitoba Study of Health and Aging, a population-based, prospective cohort study. Participants screened as cognitively intact at baseline had complete data on migraine history and all covariates at baseline and were assessed for cognitive outcomes (all-cause dementia, AD, and VaD) 5 years later. The association of exposure (lifetime history of migraines), confounding (age, gender, education, and depression), and intervening variables (hypertension, myocardial infarction, other heart conditions, stroke, and diabetes) with all-cause dementia and dementia subtypes (AD and VaD) was assessed using multiple logistic regression models. RESULTS: A history of migraines was significantly associated with both all-cause dementia (odds ratio [OR]=2.97; 95% confidence interval [CI]=1.25-6.61) and AD (OR=4.22; 95% CI=1.59-10.42), even after adjustment for confounding and intervening variables. Migraines were not significantly associated with VaD either before (OR=1.83; 95% CI=0.39-8.52) or after (OR=1.52; 95% CI=0.20-7.23) such adjustment. CONCLUSIONS: Migraines were a significant risk factor for AD and all-cause dementia. Despite the vascular mechanisms involved in migraine physiology, migraines were not significantly associated with VaD in this study. Recognition of the long-term detrimental consequences of migraines for AD and dementia has implications for migraine management, as well as for our understanding of AD etiology.

Multilingualism and Dementia Risk: Longitudinal Analysis of the Nun Study.

BACKGROUND: Multilingualism is associated with enhanced executive function and may thus prevent cognitive decline and reduce the risk of dementia. OBJECTIVE: To determine whether multilingualism is associated with delayed onset or reduced risk of dementia. METHODS: Dementia was diagnosed in the Nun Study, a longitudinal study of religious sisters aged 75+ years. Multilingualism was self-reported. Dementia likelihood was determined in 325 participants using discrete-time survival analysis; sensitivity analyses (n = 106) incorporated additional linguistic measures (idea density and grammatical complexity). RESULTS: Multilingualism did not delay the onset of dementia. However, participants speaking four or more languages (but not two or three) were significantly less likely to develop dementia than monolinguals (OR = 0.13; 95% CI = 0.01, 0.65, adjusted for age, apolipoprotein E, and transition period). This significant protective effect of speaking four or more languages weakened (OR = 0.53; 95% CI = 0.06, 4.91) in the presence of idea density in models adjusted for education and apolipoprotein E. CONCLUSION: Linguistic ability broadly was a significant predictor of dementia, although it was written linguistic ability (specifically idea density) rather than multilingualism that was the strongest predictor. The impact of language on dementia may extend beyond number of languages spoken to encompass other indicators of linguistic ability. Further research to identify the characteristics of multilingualism most salient for risk of dementia could clarify the value, target audience, and design of interventions to promote multilingualism and other linguistic training as a strategy to reduce the risk of dementia and its individual and societal impacts.