S. Riedel-Heller

Obesity and poor sleep quality – prevalences and risk factors from the LIFE-Adult-Study

Research has linked obesity to poor sleep. Yet, comprehensive large-scale studies are lacking. This study provides prevalence estimates of poor sleep quality among individuals with obesity and associated risk factors. The study sample comprised 1,416 individuals with obesity from the German population-based LIFE-Adult-Study. Assessments included age, sex, body mass index (BMI), socioeconomic status (SES), alcohol, tobacco, caffeine, depressive/anxiety symptoms and fatigue, health-related quality of life. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Associations between poor sleep and potential risk factors were analyzed using logistic regression. Poor sleep was reported by 43.5% with prevalence presenting an inverted U-shaped pattern across age groups, peaking at age 50–59 years. Poor sleep quality was associated with female sex (OR = 1.53, 95% CI = 1.15–2.03), low SES (OR = 1.65, 95% CI = 1.08–2.52), smoking (OR = 1.39, 95% CI = 1.01–1.93), frequent caffeine intake (OR = 1.60, 95% CI = 1.23–2.09), depressive symptoms (OR = 1.05, 95% CI = 1.02–1.08), symptoms of anxiety (OR = 1.15, 95% CI = 1.08–1.22) and fatigue (OR = 1.03, 95% CI = 1.01–1.04). Poor sleep quality is highly prevalent among individuals with obesity. Several additional associated factors were identified, highlighting particularly vulnerable subgroups.

Examining the Contribution of Childhood Maltreatment to the Sex Gap in Depression: Insights from the German National Cohort (NAKO).

APOE-stratified genome-wide association analyses provide insights into the genetic etiology of Alzheimers's disease.

Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E (APOE) gene ɛ2/ɛ3/ɛ4 polymorphisms remain the longstanding benchmark for genetic disease risk with a consistently large effect across studies1-10. Despite this massive signal, the exact mechanisms by which ɛ4 increases and ɛ2 decreases dementia risk remain poorly understood. Notably, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in ε4 carriers11-13, hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWASs) stratified by ε4 and ε2 carrier status. HP1BP3, SLC50A1, PTPRC, NPAS3, DDHD1, CHST9, SMYD2, PRAMEF1 and GFRA1 emerged as new genomic signals for AD risk, appearing only when stratified by APOE carrier status. DDHD1 appeared especially promising, showing protective effects in ε4 carriers, being identified as an expression quantitative trait locus and being involved in rare neuronal diseases. Such APOE-stratified insights may help understand and overcome side effects, inform clinical trial enrollment strategies, and create the scientific basis for targeted, mechanism-driven therapies in neurodegenerative diseases.

Modifizierbare Risiko- und Schutzfaktoren für Demenz: Etablierte und neue Evidenz im Überblick

Die Alzheimer-Erkrankung und andere Formen von Demenz zählen zu den schwerwiegenden Volkskrankheiten, deren gesellschaftliche und gesundheitssystemische Bedeutung in den kommenden Jahren weiter zunehmen wird. Prognosen zur Krankheitslast sind entsprechend besorgniserregend. Gleichzeitig wurden in der Forschung, insbesondere im Bereich der Risikoreduktion, erhebliche Fortschritte erzielt. So ist eine Vielzahl etablierter Schutz- und Risikofaktoren auf individueller Ebene identifiziert worden und etliche daran anknüpfende Interventionsstudien wurden durchgeführt. Zunehmend richtet sich der Fokus jedoch auf bevölkerungsbezogene Maßnahmen zur langfristigen Reduktion der Demenzfälle. Dieser Beitrag gibt einen Überblick über den aktuellen Forschungsstand. Ausgehend von der Datenlage zur Krankheitslast wird zunächst auf etablierte Risikofaktoren eingegangen. Darauf aufbauend werden neuere, bislang weniger berücksichtigte potenzielle Einflussfaktoren erläutert, bestehende Interventionsansätze zusammengefasst und die Bedeutung bevölkerungsbezogener Präventionsstrategien für Public Health und Gesundheitspolitik eingeordnet.

Exome analysis of 22,319 individuals links extremely rare copy-number variants and 22q11.21 dosage to Alzheimer risk.

Copy-number variants (CNVs) are major contributors to human disease. In Alzheimer disease (AD), APP duplications cause autosomal-dominant forms, but the role of CNVs in non-monogenic AD remains poorly characterized. We analyzed rare CNVs (frequency <1%) from 22,319 exomes (4,150 early-onset AD [EOAD, ≤65 years], 8,519 late-onset AD [LOAD], 9,650 unaffected control subjects) using harmonized calling and quality control. After identifying 17 individuals with a pathogenic CNV, we performed exome-wide and gene-set burden analyses. EOAD-affected individuals showed increased burdens of rare CNVs affecting coding genes, particularly deletions in AD-related genes. Integrated loss-of-function (LoF) analysis gathering short truncating variants with deletions showed that ABCA1 (odds ratio [OR] = 5.77 [95% confidence interval 2.25; 17.06], p = 0.0002) and ABCA7 deletions contribute to this deletion burden (OR = 2.29 [1.44; 3.65], p = 0.0006), while CTSB LoF alleles appear as candidates (OR = 5.03 [1.50; 20.71], p = 0.0089). We then performed exome-wide gene-level dosage analysis and highlighted 18 genes across five loci with a false discovery rate of <10%, including the 22q11.21 central region, where deletions were restricted to EOAD (including one de novo event) and duplications were enriched in control individuals, with intermediate frequencies in LOAD. We narrowed this locus to the SCARF2-KLHL22-MED15 region after integrating short truncating variants. Replication in 33,977 affected individuals and 362,322 control subjects confirmed association for 22q11.21 dosage with exome-wide significance (ORSCARF2 = 0.34 [0.21; 0.53]; mega-p value = 5.52 × 10-7). SCARF2 overexpression significantly increased amyloid-β uptake, congruent with duplication-associated decreased AD risk. We conclude that rare coding CNVs in a proportion of AD-associated genes and 22q11.21 deletions, including some found in DiGeorge syndrome, increase AD risk. Conversely, we identify 22q11.21 duplication as a strong AD-risk-decreasing factor.