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Objectives: To investigate the availability of Alzheimer's Centers (ACs) in US hospitals. Methods: Utilizing the American Hospital Association Annual Survey, Area Health Resource File, and US Census (n = 3251), we employed multivariable logistic regression to examine hospital, county, and regional predictors of AC availability. Results: Large hospitals (>399 beds) had approximately 14 times higher odds of having an AC than small hospitals (<50 beds; OR = 14.0; 95% CI = 6.44 – 30.46). Counties with a higher proportion of Latino residents, relative to non-Latino Whites, had lower odds of having an AC (OR =.05; 95% CI =.01 –.41). Northeastern (OR = 1.92; 95% CI = 1.15 – 3.22) and Midwestern (OR = 2.12; 95% CI = 1.34 – 3.37) hospitals had higher odds of having an AC than Southern hospitals. Discussion: To address dementia needs and disparities, investment in a national infrastructure is critical. [ABSTRACT FROM AUTHOR]

Cerebral hemodynamic alterations have been observed in apolipoprotein ε4 (APOE4) carriers at midlife, however the physiological underpinnings of this observation are poorly understood. Our goal was to investigate cerebral blood flow (CBF) and its spatial coefficient of variation (CoV) in relation to APOE4 and a measure of erythrocyte anisocytosis (red blood cell distribution width – RDW) in a middle-aged cohort. Data from 563 participants in the PREVENT-Dementia study scanned with 3 T MRI cross-sectionally were analysed. Voxel-wise and region-of-interest analyses within nine vascular regions were run to detect areas of altered perfusion. Within the vascular regions, interaction terms between APOE4 and RDW in predicting CBF were examined. Areas of hyperperfusion in APOE4 carriers were detected mainly in frontotemporal regions. The APOE4 allele differentially moderated the association between RDW and CBF, an association which was more prominent in the distal vascular territories (p – [0.01, 0.05]). The CoV was not different between the considered groups. We provide novel evidence that in midlife, RDW and CBF are differentially associated in APOE4 carriers and non-carriers. This association is consistent with a differential hemodynamic response to hematological alterations in APOE4 carriers. [ABSTRACT FROM AUTHOR]

Objectives: To assess the heterogeneity of transitions toward dependency in older adults and to explore the robustness of results to different operationalizations of dependency. Method: Using data from people aged 60 years and older from a national representative study in Uruguay (Encuesta Longitudinal de Protección Social, N = 5071), we fitted multinomial regressions adjusted by sociodemographic and health characteristics to model transitions into dependency and death. We used a harder operationalization with basic activities of daily living (Katz-dependency) and Comprehensive-dependency with basic, instrumental, and advanced activities. Results: Increasing age (RRR = 1.08, CI = [1.05; 1.12], p <.001) and having comorbidities (RRR = 2.16, CI = [1.31; 3.57], p =.003) increased the risk of transition from nondependent to dependent using Katz-dependency. Women with at least two chronic conditions have increased risk of Comprehensive-dependency (RRR = 1.79, CI = [1.15; 2.80], p =.010). Discussion: Inconsistencies in findings emerged when evaluating transitions into dependency with the different measures, which may have social care implications. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer's disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged apolipoprotein ε4 carriers (APOEε4+) were investigated. Longitudinal 3 T T1-weighted and arterial spin labelling MRI data from 158 participants (40–59 years old) in the PREVENT-Dementia study were analysed (125 two-year follow-up). Cognition was evaluated using the COGNITO battery. Cerebral blood flow (CBF) and cerebrovascular resistance index (CVRi) were quantified for the flow territories of the anterior, middle and posterior cerebral arteries. CBF was corrected for underlying atrophy and individual hematocrit. Hemodynamic measures were the dependent variables in linear regression models, with age, sex, years of education and APOEε4 carriership as predictors. Further analyses were conducted with cognitive outcomes as dependent variables, using the same model as before with additional APOEε4 × hemodynamics interactions. At baseline, APOEε4+ showed increased CBF and decreased CVRi compared to non-carriers in the anterior and middle cerebral arteries, suggestive of potential vasodilation. Hemodynamic changes were similar between groups. Interaction analysis revealed positive associations between CBF changes and performance changes in delayed recall (for APOEε4 non-carriers) and verbal fluency (for APOEε4 carriers) cognitive tests. These observations are consistent with neurovascular dysregulation in middle-aged APOEε4+. [ABSTRACT FROM AUTHOR]

Background: Multimorbidity including physical and mental illness is increasing in prevalence. We aimed to investigate the associations between physical conditions and medication use with anxiety and depression in midlife. Methods: We conducted an observational cross-sectional study of volunteers in the PREVENT Dementia study. Using logistic and linear regression, we investigated the association between increasing numbers of self-reported chronic physical conditions and medications with self-reported depression and anxiety disorder, and scores on the Center for Epidemiologic Studies Depression (CES-D) scale and Spielberger State-Trait Anxiety Inventory (STAI) state subtest. Results: Of the 210 participants, 148 (71%) were women and 188 (90%) Caucasian. The mean age was 52 (standard deviation (SD) = 5.5) years. The mean number of physical conditions was 2.2 (SD = 1.9) and medications 1.7 (SD = 2.2). Each additional physical condition was associated with increased odds of self-reported depression (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.11–1.80; p = 0.004, adjusted for age and gender) and anxiety disorder (OR 1.70, 95% CI 1.30–2.37; p < 0.001). Increasing medication use was associated with self-reported depression (adjusted OR per additional medication 1.35, 95% CI 1.08–1.71; p = 0.008) but not anxiety disorder. For each additional condition, CES-D scores increased by 0.72 (95% CI 0.11–1.33; p = 0.020) and for each extra medication, by 0.88 (95% CI 0.32–1.44; p = 0.002). There was no significant association between increasing conditions and medications with STAI scores. In models accounting for antidepressant use, all associations were attenuated. Conclusions: Having more physical conditions is associated with anxiety and depression in midlife, and taking more medications is associated with depression but not anxiety. [ABSTRACT FROM AUTHOR]

Objectives: We explore the association between different patterns of change in depressive symptoms and memory trajectories in US and European Mediterranean (Spain, France, Italy, and Israel) and non-Mediterranean (Sweden, Denmark, Netherlands, Germany, Belgium, Switzerland, and Austria) older adults. Methods: Samples consisted of 3,466 participants from the Health Retirement Study (HRS) and 3,940 participants from the Survey of Health, Aging and Retirement (SHARE). Individuals were grouped as follows: non-case depression (NO DEP), persistent depression (DEP), depression onset (ONSET), depression recovery (RECOV), and fluctuating (FLUCT). Memory was measured using immediate and delayed recall tests. Linear mixed models were used. Results: DEP and RECOV had significantly lower baseline memory scores compared to NO DEP, at intercept level. At slope level, ONSET had a significantly faster decline in both tasks compared to NO DEP. Discussion: Cross-cohort robust and consistent new empirical evidence on the association between depression onset and faster decline in memory scores is provided. [ABSTRACT FROM AUTHOR]

Objectives: To model trajectories of visuospatial reasoning measured using Kohs Block Design test under realistic missing data assumptions and evaluate their association with hazard of death. Methods: A joint longitudinal-survival model was used to estimate trajectories of visuospatial reasoning under a missing not at random assumption of participants from the Origins of Variance in the Old–Old: Octogenarian Twins study. Sensitivity analyses to missing data assumptions were conducted. Results: Visuospatial reasoning declined at constant rate. Baseline age, dementia status, education, and history of stroke were associated with visuospatial reasoning performance, but only dementia was associated with its rate of decline. Importantly, our results demonstrated an association between poorer visuospatial reasoning and increased hazard of death. Baseline age and sex were associated with risk of death. Discussion: We confirmed an association between visuospatial reasoning and death under plausible missing data assumptions. [ABSTRACT FROM AUTHOR]

Many medical (and ecological) processes involve the change of shape, whereby one trajectory changes into another trajectory at a specific time point. There has been little investigation into the study design needed to investigate these models. We consider the class of fixed effect change-point models with an underlying shape comprised two joined linear segments, also known as broken-stick models. We extend this model to include two sub-groups with different trajectories at the change-point, a change and no change class, and also include a missingness model to account for individuals with incomplete follow-up. Through a simulation study, we consider the relationship of sample size to the estimates of the underlying shape, the existence of a change-point, and the classification-error of sub-group labels. We use a Bayesian framework to account for the missing labels, and the analysis of each simulation is performed using standard Markov chain Monte Carlo techniques. Our simulation study is inspired by cognitive decline as measured by the Mini-Mental State Examination, where our extended model is appropriate due to the commonly observed mixture of individuals within studies who do or do not exhibit accelerated decline. We find that even for studies of modest size ( n = 500, with 50 individuals observed past the change-point) in the fixed effect setting, a change-point can be detected and reliably estimated across a range of observation-errors. [ABSTRACT FROM AUTHOR]

No single study has collected data over individuals' entire lifespans. To understand changes over the entire life course, it is necessary to combine data from various studies that cover the whole life course. Such combination may be methodologically challenging due to potential differences in study protocols, information available and instruments used to measure the outcome of interest. Motivated by our interest in modelling blood pressure changes over the life course, we propose the use of Bayesian adaptive splines within a hierarchical setting to combine data from several UK-based longitudinal studies where blood pressure measures were taken in different stages of life. Our method allowed us to obtain a realistic estimate of the mean life course trajectory, quantify the variability both within and between studies, and examine overall and study specific effects of relevant risk factors on life course blood pressure changes. [ABSTRACT FROM AUTHOR]

An important assumption in many linear mixed models is that the conditional distribution of the response variable is normal. This assumption is violated when the models are fitted to an outcome variable that counts the number of correctly answered questions in a questionnaire. Examples include investigations of cognitive decline where models are fitted to Mini Mental State Examination scores, the most widely used test to measure global cognition. Mini Mental State Examination scores take integer values in the 0-30 range, and its distribution has strong ceiling and floor effects. This article explores alternative distributions for the outcome variable in mixed models fitted to mini mental state examination scores from a longitudinal study of ageing. Model fit improved when a beta-binomial distribution was chosen as the distribution for the response variable. [ABSTRACT FROM AUTHOR]

To quantify inconsistent self-reporting of chronic conditions between the baseline (2011–2015) and first follow-up surveys (2015–2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity.Community-dwelling adults aged 45–85 years in the baseline and first follow-up surveys were included (n = 45,184). At each survey, participants self-reported whether they ever had a physician diagnosis of 35 chronic conditions. Identifiable inconsistent responses were enumerated.32–40% of participants had at least one inconsistent response across all conditions. Illness-related information (e.g., taking medication) resolved most inconsistent responses (>93%) while computer-assisted software asking participants to confirm their inconsistent disease status resolved ≤53%. Using these adjudication methods, multimorbidity prevalence at follow-up increased by ≤1.6% compared to the prevalence without resolving inconsistent responses.Inconsistent self-reporting of chronic conditions is common but may not substantially affect multimorbidity prevalence. Future research should validate methods to resolve inconsistencies. [ABSTRACT FROM AUTHOR]