The possibility that lifestyle factors may delay or accelerate cognitive decline in aging has garnered significant attention and a considerable body of research has formed. However, investigating the relations between social engagement and cognitive function in aging have been somewhat equivocal in their findings and there is a lack of understanding of the mechanisms by which social engagement may impact cognitive function and the role of factors limiting social engagement. The aim of this dissertation was to build on current understanding of how specific aspects of social relationships relate to cognitive functioning in older adulthood and how these aspects are affected by challenges and barriers to social participation. This dissertation is comprised of three studies addressing several specific research questions. Study one (Chapter 2) examined whether relations with cognitive performance over time differ for structural aspects of social relationships (social network and social contact) versus functional/subjective aspects of social relationships (loneliness and social support) and whether the associations are between cognitive performance and stable, “trait-like” components of social relationships or fluctuating “state-like” components of these constructs, using autoregressive latent trajectory modeling of data from the Health and Retirement Study. Study two (Chapter 3) used a multilevel modeling approach to examine whether the spouses/partners of individuals diagnosed with Alzheimer’s disease or dementia experience a within person decline in cognitive performance and whether changes in structural and functional/subjective aspects of social relationships interacted with a spouses’ diagnosis of memory disease to predict within person change in cognitive performance. Study three (Chapter 4) investigated whether rejection sensitivity, social avoidance, and fears of negative social evaluations were predictive of lack of social participation and loneliness in a sample of Vancouver Island older adults. These factors have previously been investigated in younger adults as risk factors for loneliness and social withdrawal, but social isolation in older adulthood is often attributed to lack of social opportunities. This dissertation demonstrates the importance of considering precise aspects of social relationships, including barriers to social participation, and their relations to cognitive functioning. / Graduate / 2019-12-12

La nutrition pourrait être un facteur de prévention de la démence, pour laquelle il n’existe pas à ce jour de traitement étiologique identifié. L’objectif de la thèse était d’étudier la relation entre nutrition et vieillissement cérébral chez 1796 participants bordelais, âgés de 65 ans et plus, de la cohorte des 3 Cités, avec un intérêt particulier pour les acides gras. Compte-tenu de la nature multidimensionnelle de l’alimentation, plusieurs approches complémentaires ont été utilisées. A l’échelle du comportement alimentaire, des profils de consommation spontanément observés ont été identifiés par des méthodes exploratoires. Les sujets âgés du profil « sain », consommateurs de plus de 3,5 portions de poisson par semaine chez les hommes et de plus de 6 portions quotidiennes de fruits et légumes chez les femmes, ont montré une meilleure santé cognitive et psychologique. L’adhérence à un régime de type méditerranéen, mesurée par un score construit selon une approche confirmatoire, a été associée à un moindre déclin cognitif global après 5 ans de suivi. A l’échelle du biomarqueur de nutriment, la proportion plasmatique d’acide eicosapenténoïque (EPA), acide gras oméga-3 à longue chaîne, a été associée à une diminution du risque de démence, et le ratio des acides gras oméga-6 / oméga-3 à une augmentation du risque, particulièrement chez les sujets déprimés. L’EPA a également été associé à une diminution du déclin de la mémoire de travail chez les sujets déprimés ou porteurs de l’allèle e4 de la protéine ApoE, et l’acide docosahexaénoïque à une diminution du déclin uniquement chez les porteurs de l’ApoEe4. / In the absence of identified etiologic treatment for dementia, the potential preventive role of nutrition may offer an interesting perspective. The objective of the thesis was to study the association between nutrition and brain aging in 1796 subjects, aged 65 years or older, from the Bordeaux sample of the three-City study, with a particular emphasis on fatty acids. Considering the multidimensional nature of nutritional data, several complementary strategies were used. At the global diet level, dietary patterns actually observed in the population were identified by exploratory methods. Older subjects from the “healthy” pattern, who consumed more than 3.5 weekly servings of fish in men and more than 6 daily servings of fruits and vegetables in women, showed a better cognitive and psychological health. Adherence to the Mediterranean diet, measured according to a score-based confirmatory method, was associated with slower global cognitive decline after 5 years of follow-up. At the nutrient biomarker level, higher plasma eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid, was associated with a decreased dementia risk, and the omega-6-to-omega-3 fatty acids ratio to an increased risk, particularly in depressed subjects. EPA was also related to slower working memory decline in depressed subjects or in carriers of the e4 allele of the ApoE gene. Docosahexaenoic acid was related to slower working memory decline only in ApoEe4 carriers.

This study was designed to determine to what extent provision of personally relevant information and sensory cues would agree between Recipient and Informant for selection of memory book content. Six dyads married to each other an average of 29.17 years (SD = 10.03), between the ages of 43 and 70 years (Mean = 57; SD = 8.39), and cognitively competent (i.e., no diagnosis of cognitive impairment) participated. Participants completed questionnaires independently and provided personally relevant information/memories, aversions towards select memories/topics, and sensory cues on behalf of themselves (as “Recipient) and their spouse (as “Informant”). For provision of personally relevant information/memories, Informant and Recipient was 44.58% in agreement (SD = 14.99). For provision of aversions towards select memories/topics, Informant and Recipient was 24.86% in agreement (SD = 30.81). For provision of sensory cues, Informant and Recipient was 19.6% in agreement (SD = 30.81). Findings suggest that memory books made by others may not include the most important memories of the Recipient, thereby limiting the effectiveness of the memory book. Therefore, efforts should be made to encourage individuals to create a memory book while cognitively competent or share their most meaningful memories with the person who is most likely to make them a memory book if they should need one in the future.

The negative effects of cognitive decline and impairment can be devastating for older adults and their families, and extremely costly for the healthcare system and the society. Cognitive training aims to maintain or improve cognition by utilizing repetitive tasks that target specific cognitive skills. The majority of cognitive training studies in healthy older adults involved home-based, individual, computerized approach or onsite, group, paper-and-pencil format. These approaches may not be suitable for individuals with serious health or mobility issues, caregiving responsibilities, limited transportation, or limited computer or internet access. A novel, home-based, self-administered cognitive training intervention was developed to address these barriers. It involves two older adults taking turns to administer paper-and-pencil tasks to one another. The purpose of the study was to evaluate feasibility and participant acceptability of this novel approach to cognitive training. Eighteen participants (9 dyads) 65-91 years (M = 75.94, SD = 7.66) underwent assessment and began intervention. Assessment included measures of cognitive skills and self-reported quality of life, health status, and daily functioning. Four dyads were married couples who had sessions at home. Other dyads met at various public locations and included friends, neighbors, or unfamiliar older adults connected by the researcher. Fourteen participants (7 dyads) completed cognitive training intervention that included 9-24 sessions (M = 15.14, SD = 5.30) over 4-21 weeks (M = 12.21, SD = 5.44), post-intervention assessment, and detailed interviews. Quantitative data demonstrated that the sample did not decline on any cognitive measures and exhibited improvement on visuospatial skills and delayed visual memory (Cohen’s d = .67 & -1.10). Additional analyses revealed that the results were mainly attributable to improvement in females (Cohen’s d = -1.84 & -1.35), who demonstrated weaknesses in these cognitive skills at baseline. The participants reported that the dyadic approach was flexible, convenient, and enjoyable. They also provided valuable feedback and suggestions for modifying the content and other aspects of the intervention. The findings suggest that dyadic cognitive training is feasible and well-received by older adults. Those with weaknesses in cognitive domains may show larger gains in respective domains and benefit most from cognitive training.

Le déclin des performances cognitives au cours du vieillissement représente une problématique majeure dans le contexte actuel de vieillissement de la population. Le processus de vieillissement cognitif est complexe et multifactoriel. Dans la première partie de nos travaux, nous nous sommes intéressés particulièrement au rôle du diabète de type 2 dans le déclin des fonctions cognitives à partir des données longitudinales de la cohorte Whitehall II. Les performances cognitives ont été évaluées à travers une batterie de tests neuropsychologiques chez des individus âgés de 45 à 70 ans lors du premier passage de tests cognitifs. Nous avons ainsi observé que le diabète de type 2 à l'inclusion dans l'étude était associée à de moins bonnes performances cognitives et à un déclin cognitif plus important au cours du suivi, en particulier chez des patients diabétiques de type 2 de longue date. Nous avons observé une relation entre le mauvais équilibre glycémique et le déclin accéléré des fonctions cognitives. Dans la deuxième partie de ce travail de thèse, nous nous sommes intéresses au rôle potentiellement protecteur des médicaments antidiabétiques sur le déclin cognitif dans le cadre d'une méta-analyse des essais contrôles randomisés. Les résultats de la méta-analyse indiquent que le contrôle glycémique strict n'est pas associé à une diminution du risque de déclin cognitif chez les patients diabétiques de type 2. Nos résultats sont en faveur d'une contribution du diabète de type 2 diagnostiqué en milieu de vie au déclin des fonctions cognitives et participent à une meilleure compréhension de ce processus. / Cognitive decline represents a major issue given the current context of population aging. The cognitive aging process is complex and multifactorial. In first part of our work, we addressed in particular the contribution of type 2 diabetes to cognitive decline, based on longitudinal data from the Whitehall 2 study. Cognitive function was assessed through a battery of neuropsychological tests in participants aged 45 to 70 years old at the beginning of cognitive testing. We observed that baseline type 2 diabetes was associated with lower cognitive performance at baseline and greater decline over follow-up, particularly in patients with longer duration of type 2 diabetes. We observed a relationship between poor glycemic control and faster cognitive decline. In second part of our work, we were interested in the potentially protective role of antidiabetic medications on cognitive decline in a meta-analysis of randomized controlled trials. The meta-analysis indicated that intensive glycemic control was not associated with slower cognitive decline. Our results support the hypothesis of a contribution of type 2 diabetes to cognitive decline in midlife and contribute to improve our understanding of this process.

BACKGROUND: The prevalence of Alzheimer’s disease (AD) and other types of dementia is expected to drastically increase between now and midcentury because of the aging baby boomer population. It is projected that by 2030, 74 million people aged 65 and older will comprise nearly 20% of the population (United States Census Bureau, 2017). By 2060, it is estimated that about 13.8 million people will have AD. In 2020, the estimated total health care costs for treating individuals with AD in 2020 is $305 billion (Wong, 2020). As the population ages, the cost is expected to increase to more than $1 trillion. This significant economic and health care burden could be greatly alleviated by the development of a treatment that would delay the onset of the disease or prevent the disease altogether. Increasing evidence supports cardiovascular health being linked to the health of the brain. Diabetes is a particular risk factor that increases the likelihood of cardiovascular disease and is consequently associated with a higher risk of developing AD and other dementias. AIM: The aim of this study was to determine the association between persistent high blood glucose during midlife to late life and the risk of incident dementia and AD. METHODS: This study included 1287 Framingham Offspring participants (669 women, mean age 68.6 ± 5.7 years) who were free of dementia and attended 5 consecutive examinations at 4-year intervals starting at midlife (Exam 3: 1983–1987, mean age 54.6 ± 5.8 years) until late life (Exam 7: 1998–2001, mean age 68.6 ± 5.7 years). These participants were subsequently followed up for incident dementia after a period of time (mean 14 ± 4.5 years). Based on the resulting data, this study examined the effect of midlife diabetes (fasting blood glucose level ≥ 126 mg/dL), late-life diabetes, 10-mg/dL incremental increases in fasting blood glucose (FBG), persistence of diabetes during midlife to late life, and a steep increase in FBG from midlife to late life over an 18-year exposure period. Further stratified analysis was completed on a subgroup of participants with a steep incline in FBG to determine if there was an interaction effect with apolipoprotein E4 (APOE4) carrier status. RESULTS: During the follow-up period, 172 participants developed dementia, and of these cases, 135 participants had AD. Multivariable Cox proportional hazards models showed that persistent high FBG was associated with greater than 2-fold increase in risk of both incident dementia (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.37-3.33) and AD ([HR] 2.18, 95% [CI] 1.33-3.57) after adjusting for age, sex, education, APOE4, prevalent cardiovascular disease (CVD), and midlife diabetes treatment. In addition, individuals who experienced a steep increase in their FBG from Exam 3 to Exam 7 were associated with an increased risk of developing AD (p value = 0.022). Further stratification by APOE4 carrier status with a steep increase in FBG revealed that APOE4 non-carriers were associated with an approximate 2-fold increased risk for developing incident dementia ([HR] 1.90, 95% [CI] 1.12-3.16; p value < 0.05) and AD ([HR] 2.30, 95% [CI] 1.28-4.06; p value < 0.05). CONCLUSIONS: Persistent high blood glucose was associated with an increased risk for developing incident dementia and AD in a community-based cohort. A steep increase in FBG during midlife to late life also increased the risk for developing dementia and AD in this cohort. These data support the potential of sustained cognitive benefits from lower blood glucose levels in midlife but also suggest that sharp increases in blood glucose levels in older adults may be a risk marker for dementia and AD.

Dementia is a growing burden for society, and it is of interest to discover it at an early stage. Both subjective cognitive decline (SCD) and subjective olfactory decline (SOD) has been associated with future cognitive decline and dementia. However, subjective measures have often been criticized and are still not fully understood. I aimed to examinate the frequency of SCD and SOD and whether they are likely to measure different things and what their longitudinal effects are. The baseline sample (N=784, 35-90 years, 51% female) were split into reported SCD, SOD, combined subjective olfactory and cognitive decline, and controls. Between-subjects and within-subjects statistical tests were conducted on a subset of participants (N=307, 45 to 90 years, 52% female) comparing SCD and SOD and their olfactory ability, cognitive performance, and demographics. In the baseline sample, a total of 21.1% reported a SOD whereas only 9.9% reported a SCD, only 2.7% reported both. SOD individuals had an emerged olfactory decline at follow up, their olfactory performance was associated with performance in several cognitive tests, this was not the case for the SCD individuals. The SOD and the SCD groups differ from each other, and they appear to be rather independent from each other. They might be complementary in understanding the aging brain.

Studies have reported mixed results for people with or without diabetes with cognitive decline or Alzheimer's disease (AD). Cognitive decline and AD among people with diabetes will be the focus of much discussion since results have been controversial. The study examined whether diabetes is associated with cognitive decline and whether it is an independent risk factor for the development of AD among elderly residents of Cache County, Utah. Results revealed an association between diabetes and a lower average Modified Mini Mental State Examination (3MS) score of nearly a point lower at baseline. Results also showed an association between diabetes and an increased risk of incident AD compared with non-diabetes for men but not for women. The interaction between diabetes, gender, and risk of AD should be explored further.

Previous studies have found nutritional status to predict better functional and cognitive ability in dementia. The current study investigated the relationship between nutritional status and progression of neuropsychological impairment in a U.S. sample of persons with dementia. Participants were studied for up to 6 years in the population-based Cache County, UT, study. Baseline sample included 240 persons with dementia (71.3% Alzheimer’s disease, 52.1% female). Mean (SD) age and dementia duration at baseline was 85.6 (5.2) and 3.4 (1.9) years, respectively. Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological test battery and Boston Naming Test (30-item) were administered annually. Nutritional status was assessed using a modified Mini Nutritional Assessment (mMNA). Components of nutritional status were chosen for further investigation (dietary intake and BMI). Linear mixed effects models examined change in nutritional status and food consumption over time as well as the association between mMNA and its components (time-varying) with each neuropsychological measure and rate of decline over time. The following covariates were tested as appropriate: dementia type, gender, age of dementia onset and duration (at baseline), education, neuropsychiatric symptoms, caregiver coresidence, place of residence, overall health, and dementia severity. mMNA scores decreased by .22 pts/year (p = .006), though this was confounded by dementia severity (β = -.12, p = .108). Consumption of carbohydrates (β = -.09), protein (β = -.07) and fruit/vegetables (β = -.08) also declined over time, all p < .05). Better nutritional status was associated with better neuropsychological test scores across all visits in verbal learning (β = .23), praxis drawing (β = .23), praxis memory (β = .08), verbal fluency (β = .34) and confrontation naming (β = .31), while mMNA predicted rate of decline in verbal recognition memory (β = .13); all p < .001, with the inclusion of covariates. Higher protein intake was associated with worse verbal learning, while higher BMI predicted better scores on all neuropsychological tests except for confrontation naming. The results emphasize the importance of nutritional status in dementia and raises the possibility of nutritional interventions that may improve patient outcomes.

Objectives: Our goal was to explore the association between vision with cognitive change scores and incident depression. Methods: A 3-year prospective cohort study was performed. Incident depression was defined using a cut-off score of 10 on the Center for Epidemiologic Studies Depression scale. Cognitive change was examined by calculating the difference between baseline and follow-up cognitive tests scores. Multivariable Poisson and linear regression were used. Results: Cataract was associated with incident depression (relative risk=1.20, 95% confidence interval 1.05, 1.37). Visual impairment was associated with the 3-year change in Rey Auditory Verbal Learning Test (RAVLT) (β=-0.18, 95% CI= -0.28, -0.07), RAVLT-Delayed (β=-0.13, 95% CI= -0.25, -0.02), and Animal Naming Test (β=-0.95, 95% CI= -1.44, -0.45) scores. Glaucoma was associated with 3-year Mental Alternation Test change scores (β=-0.40, 95% CI -0.77, -0.04). Conclusions: Cataract was associated with increased depression risk. VI and glaucoma are associated with 3-year changes in cognitive test scores.