Cardiovascular Risk Factors and Risk of Alzheimer Disease and Mortality: A Latent Class Approach

BackgroundCardiovascular risk factors co‐occur with one another, and little is known about the extent of their clustering and risk of Alzheimer disease (AD). We identify groups of cardiovascular risk factors in cognitively normal individuals and investigate between‐group differences in incident AD and death.Methods and ResultsCognitively normal individuals were recruited from the National Alzheimer's Coordinator Center. A latent class analysis was conducted with hypertension, hypercholesterolemia, heart condition, stroke, smoking history, diabetes, and high body mass index. Between‐group differences in the incidence of AD, mortality, and mortality‐adjusted AD were investigated. This study included 12 412 cognitively normal individuals (average follow‐up, 65 months). Three groups were identified: (1) low probabilities of cardiovascular risk factors (reference; N=5398 [43%]), (2) hypertension and hypercholesterolemia (vascular‐dominant; N=5721 [46%]), and (3) hypertension, hypercholesterolemia, diabetes, and high body mass index (vascular‐metabolic; N=1293 [10%]). Both vascular groups were significantly older, had more men, were slightly less educated, and were slightly more cognitively impaired than the reference group (all P<0.05). However, only the vascular‐metabolic group had a significantly younger age of death compared with the reference group (84.3 versus 88.7 years, P<0.001). Only the vascular‐dominant group had a greater incidence of AD (odds ratio [OR], 1.30; P<0.001) compared with the reference group. Mortality was greater in the vascular‐dominant (OR, 3.26; P<0.001) and vascular‐metabolic groups (OR, 1.84; P=0.02). Mortality‐adjusted AD was greater in the vascular‐dominant (OR, 1.54; P=0.02) and vascular‐metabolic groups (OR, 1.46; P=0.04).ConclusionsThree distinct cardiovascular risk factor groups were identified in cognitively normal elderly individuals. Only the vascular‐dominant group was associated with a greater incidence of AD. Selective mortality may contribute to the attenuated association between the vascular‐metabolic group and incident AD.publishedVersio

Dynamics between psychological distress and body mass index throughout adult life; evidence from 3 large cohort studies

Background: Associations between body mass index (BMI) and psychological distress (PD) have been reported; however, few longitudinal studies have accounted for likely life-course differences in BMI and PD stability, consistency, and their interplay across time. Methods: Via random intercepts cross-lagged panel models, we assessed the predictive effects (from BMI to PD or vice-versa) across the last two centuries in the Coronary Artery Risk Development in Young Adults [CARDIA, beginning in 1985-6] study using the Center for Epidemiological Studies-Depression Scale [CES-D], and in the National Child Development Study [NCDS, beginning in 1958] and British Cohort Study [BCS, beginning in 1970] using the Malaise Inventory [MI]), assessed at least 4 times in adult life. Findings: In CARDIA (n = 4724), NCDS58 (n = 7149) and BCS70 (n = 5967), autoregressive effects were stronger for BMI than for PD, meaning that carry-over effects from one occasion to the next were larger for BMI than for PD. Small interindividual correlations between traits of higher BMI and higher PD were identified among females (rfemale<|0⋅2|) but not males (rmale<|0⋅03|) in CARDIA and NCDS. Cross-lagged effects were very weak or close to zero (standardized effects η<|0⋅1|). Interpretation: In the United States, depressive symptoms and BMI were positively correlated at the trait level among females. In the United Kingdom, relationships between PD and BMI were inconsistent between generations, with effect sizes of unlikely clinical importance, indicating negligible dominance of an intraindividual effect of BMI on PD or vice versa.publishedVersio

The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment

BACKGROUND: Activation of indoleamine 2,3-dioxygenase (IDO) and higher concentrations of several kynurenine metabolites have been observed post-stroke, where they have been associated with increased mortality. While lower tryptophan or a higher ratio of kynurenine/tryptophan (K/T) in peripheral blood have been associated with dementia and the severity of cognitive symptoms in Alzheimer's disease, the association between K/T ratios and post-stroke cognitive impairment (PSCI) has not been investigated. METHODS: Patients were recruited from the acute stroke unit of a general hospital within 1 month post-stroke. Assessments included the Standardized Mini-Mental State Examination (sMMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Tryptophan and kynurenine concentrations were determined by high-performance liquid chromatography. RESULTS: A total of 41 patients with ischemic stroke ([mean ± SD] age 72.3 ± 12.2 years, 53.7% male, sMMSE 25.6 ± 4.1, NIHSS 7.27 ± 5.55) were recruited. Higher K/T ratios were associated with lower post-stroke global cognition (i.e. sMMSE scores; β = -.327, P = .037). A backward stepwise elimination linear regression (F(1,40)=6.15, P=.005, adjusted R(2)=.205) showed that the highest K/T ratio tertile (β = -.412, P = .006) predicted lower sMMSE scores, controlling for age (β = -.253, p = .081), with NIHSS (β = -.027, P = 0.859), and lesion volume (β = -.066, P = 0.659) removed from the model. In receiver operating characteristic analysis, a K/T ratio of 78.3 μmol/mmol (top tertile) predicted significant cognitive impairment (sMMSE score ≤ 24) with 67% sensitivity and 86% specificity (area under the curve = 0.730, p = .022). CONCLUSIONS: These data suggest an inflammatory response characterized by IDO activation may be relevant to the development of PSCI. Since the neuroactivity of kynurenine metabolites may be amenable to pharmacotherapeutic intervention, the K/T ratio may be a clinically important biomarker

Assessing Music Perception in Young Children: Evidence for and Psychometric Features of the M-Factor

Given the relationship between language acquisition and music processing, musical perception (MP) skills have been proposed as a tool for early diagnosis of speech and language difficulties; therefore, a psychometric instrument is needed to assess music perception in children under 10 years of age, a crucial period in neurodevelopment. We created a set of 80 musical stimuli encompassing seven domains of music perception to inform perception of tonal, atonal, and modal stimuli, in a random sample of 1006 children, 6–13 years of age, equally distributed from first to fifth grades, from 14 schools (38% private schools) in So Paulo State. The underlying model was tested using confirmatory factor analysis. A model encompassing seven orthogonal specific domains (contour, loudness, scale, timbre, duration, pitch, and meter) and one general music perception factor, the “m-factor,” showed excellent fit indices. The m-factor, previously hypothesized in the literature but never formally tested, explains 93% of the reliable variance in measurement, while only 3.9% of the reliable variance could be attributed to the multidimensionality caused by the specific domains. The 80 items showed no differential item functioning based on sex, age, or enrolment in public vs. private school, demonstrating the important psychometric feature of invariance. Like Charles Spearman's g-factor of intelligence, the m-factor is robust and reliable. It provides a convenient measure of auditory stimulus apprehension that does not rely on verbal information, offering a new opportunity to probe biological and psychological relationships with music perception phenomena and the etiologies of speech and language disorders

Dynamic relationships between depressive symptoms and insulin resistance over 20 years of adulthood

Background. Bidirectional longitudinal relationships between depression and diabetes have been observed, but the dominant direction of their temporal relationships remains controversial. Methods. The random-intercept cross-lagged panel model decomposes observed variables into a latent intercept representing the traits, and occasion-specific latent ‘state’ variables. This permits correlations to be assessed between the traits, while longitudinal ‘cross-lagged’ associations and cross-sectional correlations can be assessed between occasion-specific latent variables. We examined dynamic relationships between depressive symptoms and insulin resistance across five visits over 20 years of adulthood in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Possible differences based on population group (Black v. White participants), sex and years of education were tested. Depressive symptoms and insulin resistance were quantified using the Center for Epidemiologic Studies Depression (CES-D) scale and the homeostatic model assessment for insulin resistance (HOMA-IR), respectively. Results. Among 4044 participants (baseline mean age 34.9 ± 3.7 years, 53% women, 51% Black participants), HOMA-IR and CES-D traits were weakly correlated (r = 0.081, p = 0.002). Some occasion-specific correlations, but no cross-lagged associations were observed overall. Longitudinal dynamics of these relationships differed by population groups such that HOMAIR at age 50 was associated with CES-D score at age 55 (β = 0.076, p = 0.038) in White participants only. Longitudinal dynamics were consistent between sexes and based on education. Conclusions. The relationship between depressive symptoms and insulin resistance was best characterized by weak correlations between occasion-specific states and enduring traits, with weak evidence that insulin resistance might be temporally associated with subsequent depressive symptoms among White participants later in adulthood.publishedVersio

Dynamic relationships between depressive symptoms and insulin resistance over 20 years of adulthood

Background Bidirectional longitudinal relationships between depression and diabetes have been observed, but the dominant direction of their temporal relationships remains controversial. Methods The random-intercept cross-lagged panel model decomposes observed variables into a latent intercept representing the traits, and occasion-specific latent ‘state’ variables. This permits correlations to be assessed between the traits, while longitudinal ‘cross-lagged’ associations and cross-sectional correlations can be assessed between occasion-specific latent variables. We examined dynamic relationships between depressive symptoms and insulin resistance across five visits over 20 years of adulthood in the population-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Possible differences based on population group (Black v. White participants), sex and years of education were tested. Depressive symptoms and insulin resistance were quantified using the Center for Epidemiologic Studies Depression (CES-D) scale and the homeostatic model assessment for insulin resistance (HOMA-IR), respectively. Results Among 4044 participants (baseline mean age 34.9 ± 3.7 years, 53% women, 51% Black participants), HOMA-IR and CES-D traits were weakly correlated (r = 0.081, p = 0.002). Some occasion-specific correlations, but no cross-lagged associations were observed overall. Longitudinal dynamics of these relationships differed by population groups such that HOMA-IR at age 50 was associated with CES-D score at age 55 (β = 0.076, p = 0.038) in White participants only. Longitudinal dynamics were consistent between sexes and based on education. Conclusions The relationship between depressive symptoms and insulin resistance was best characterized by weak correlations between occasion-specific states and enduring traits, with weak evidence that insulin resistance might be temporally associated with subsequent depressive symptoms among White participants later in adulthood

State, trait, and accumulated features of the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) in mild Alzheimer's disease

Background The Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog) is used to assess decline in memory, language, and praxis in Alzheimer's disease (AD). Methods A latent state–trait model with autoregressive effects was used to determine how much of the ADAS-Cog item measurement was reliable, and of that, how much of the information was occasion specific (state) versus consistent (trait or accumulated from one visit to the next). Results Participants with mild AD (n = 341) were assessed four times over 24 months. Praxis items were generally unreliable as were some memory items. Language items were generally the most reliable, and this increased over time. Only two ADAS-Cog items showed reliability >0.70 at all four assessments, word recall (memory) and naming (language). Of the reliable information, language items exhibited greater consistency (63.4% to 88.2%) than occasion specificity, and of the consistent information, language items tended to reflect effects of AD progression that accumulated from one visit to the next (35.5% to 45.3%). In contrast, reliable information from praxis items tended to come from trait information. The reliable information in the memory items reflected more consistent than occasion-specific information, but they varied between items in the relative amounts of trait versus accumulated effects. Conclusions Although the ADAS-Cog was designed to track cognitive decline, most items were unreliable, and each item captured different amounts of information related to occasion-specific, trait, and accumulated effects of AD over time. These latent properties complicate the interpretation of trends seen in ordinary statistical analyses of trials and other clinical studies with repeated ADAS-Cog item measures

Treatment pathways of Alzheimer in Nigeria

Alzheimer poses lots of challenges in Low and Middle Income Countries, especially in Nigeria. Globally, the causes of Alzheimer are poorly understood. Cultural factors affect the preference of mental health treatment for treating people living with Alzheimer's disease (PLWA However, Alzheimer's and its gender differentials have been given little consideration in particular. Twenty-four in-depth study was conducted with caregivers and family members/ relatives of people living with Alzheimer's (PLWA) residing in the study area. 52.2 percent of respondents were female out of the total while 45.8 percent were male. For male respondents, 40.4%; 49.4 %; 49.2%; 35 % and 28.3% indicated spiritual preference of mental health counseling; traditional; medical practitioner; both traditional and spiritual and psychiatrist respectively. On the other hand, 59.6%; 50.6%; 50.8%; 65% and 70.7% of female respondents indicated spiritual; traditional; medical practitioner; both traditional and spiritual and psychiatrist respectively. This research found that gender disparities primarily affected the mental health intervention care pathways. The availability of mental health resources to support adult mental health were key factors which could influence mental health status