Association of CSF biomarkers with MRI brain changes in Alzheimer's disease.

The relation between cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and magnetic resonance imaging (MRI) measures is poorly understood in cognitively healthy individuals from the general population. Participants' (n = 226) mean age was 70.9 years (SD = 0.4). CSF concentrations of amyloid beta (Aß)1-42, total tau (t-tau), phosphorylated tau (p-tau), neurogranin, and neurofilament light, and volumes of hippocampus, amygdala, total basal forebrain (TBF), and cortical thickness were measured. Linear associations between CSF biomarkers and MRI measures were investigated. In Aß1-42 positives, higher t-tau and p-tau were associated with smaller hippocampus (P = 0.001 and P = 0.003) and amygdala (P = 0.005 and P = 0.01). In Aß1-42 negatives, higher t-tau, p-tau, and neurogranin were associated with larger TBF volume (P = 0.001, P = 0.001, and P = 0.01). No associations were observed between the CSF biomarkers and an AD signature score of cortical thickness. AD-specific biomarkers in cognitively healthy 70-year-olds may be related to TBF, hippocampus, and amygdala. Lack of association with cortical thickness might be due to early stage of disease.

Passive and active suicidal ideation in a population-based sample of older adults: Associations with polygenic risk scores of relevance for suicidal behavior.

Introduction: There are few studies investigating genetic factors related to suicidal ideation or behavior in older adult populations. Our aim was to test associations between passive and active suicidal ideation and polygenic risk scores (PRSs) for suicidality and other traits of relevance for suicidality in old age (i.e. depression, neuroticism, loneliness, Alzheimer's disease, cognitive performance, educational attainment, and several specified vascular diseases) in a population-based sample aged 70 years and older. Methods: Participants in the prospective H70 study in Gothenburg, Sweden, took part in a psychiatric examination that included the Paykel questions on active and passive suicidal ideation. Genotyping was performed with the Neurochip (Illumina). After quality control of the genetic data the sample included 3467 participants. PRSs for suicidality and other related traits were calculated based on summary statistics from recent GWASs of relevance. Exclusion of persons with dementia or incomplete data on suicidal ideation yielded 3019 participants, age range 70-101 years. Associations between past year suicidal ideation (any level) and selected PRSs were analysed using general estimation equation (GEE) models, adjusted for sex and age. Results: We observed associations between passive/active suicidal ideation and PRSs for depression (three versions), neuroticism, and general cognitive performance. After excluding individuals with current major depressive disorder (MDD), similar associations were seen with PRS for neuroticism, general cognitive performance and two PRSs for depression. No associations were found between suicidal ideation and PRSs for suicidality, loneliness, Alzheimer's disease, educational attainment, or vascular disease. Discussion: Our results could indicate which types of genetic susceptibility that are of importance for suicidality in old age, and these findings can help to shed light on potential mechanisms that may be involved in passive and active suicidal ideation in late-life, also in those with no current MDD. However, due to the limited sample size, the results need to be interpreted with caution until replicated in larger samples.

High polygenic risk score for exceptional longevity is associated with a healthy metabolic profile.

Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual's polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40-69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55-85 years), Older Australian Twins Study (n = 539, 65-90 years) and Sydney Memory and Ageing Study (n = 925, 70-90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70-93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22-30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10-42) and its components (p < 2.30 × 10-8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.

Accuracy of 12 short versions of the Geriatric Depression Scale to detect depression in a prospective study of a high-risk population with different levels of cognition.

OBJECTIVES: To determine the accuracy of 12 previously validated short versions of the Geriatric Depression Scale (GDS) to detect major depressive disorder (MDD) in a high-risk population with and without global cognitive impairment. DESIGN: Cross-sectional study. SETTING: Five hospitals, Western Sweden. PARTICIPANTS: Older adults (age ≥70 years, n = 60) assessed at a home visit 1 year after hospital care in connection with suicide attempt. MEASUREMENTS: Depression symptoms were rated using the established 15-item GDS. Eleven short GDS versions identified by a recent systematic review were derived from this administered version. Receiver operating characteristic curves and area under the curve (AUC) for the identification of MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were obtained for each version. The Youden Index optimal criterion was used to determine the appropriate cutoffs. Analyses were repeated after stratification by cognitive status (Mini Mental State Examination score ≤24 and >24) for the best performing GDS short versions and the established 15-item GDS. RESULTS: The 7-item GDS according to Broekman et al. (), with a cutoff 3, was the most accurate among the 12 short versions (AUC 0.90, 95% confidence interval 0.80-1.00), identifying MDD with sensitivity 88% and specificity 81%. The cutoff score remained consistent in the presence of global cognitive impairment, which was not the case for the standardized 15-item GDS. CONCLUSION: The Broekman 7-item GDS had high accuracy to detect MDD in this prospective clinical cohort at high risk for MDD. Further testing of GDS short versions in diverse settings is required.

Depression in relation to sex and gender expression among Swedish septuagenarians-Results from the H70 study.

OBJECTIVE: Little is known about the role of gender expression (femininity, masculinity, or androgyny) in relation to sex differences in depression. This study tested if gender expression was associated with depression and burden of depressive symptoms in a 70-year-old population. METHODS: A cross-sectional population-based sample of 70-year-olds from The Gothenburg H70 Birth Cohort Study (n = 1203) was examined in 2014-16. Data were collected using psychiatric examinations and structured questionnaires, including the Positive-Negative Sex-Role Inventory to assess gender expression. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders criteria, and symptom burden was assessed with Montgomery Åsberg Depression Rating Scale (MADRS). RESULTS: Gender expression was related to MADRS score and depression diagnosis. In fully adjusted models, feminine traits with low social desirability (FEM-) were associated with a higher MADRS score (R2 0.16; B 0.16; CI 0.1-0.2), while androgyny (t ratio) (R2 0.12; B 0.42; CI 0.1-0.7) and masculine traits with high social desirability (MAS+) (R2 0.13; B -0.06; CI -0.1--0.01) were associated with a lower MADRS score. Also, feminine traits with low social desirability (FEM-) were positively associated with depression (OR 1.04; CI 1.01-1.1). No associations between depression and masculinity or androgyny were observed in adjusted models. There were no interactions between sex and gender expression in relation to depression or MADRS score, indicating that the effects of gender expression were similar in men and women. CONCLUSIONS: We found that gender expression was associated to both depression and burden of depressive symptoms. More specifically, we found that femininity was associated to higher levels of depression, irrespective of biological sex. In addition, masculinity and androgyny were associated with lower levels of depression. These results highlight the importance of taking gender expression into consideration when studying sex differences in depression among older populations in future studies.