No Strong Association between the Apolipoprotein E E4 Allele and Glaucoma: A Multicohort Study.

Purpose: To elucidate a potential association between the apolipoprotein E (APOE) E4 allele and glaucoma prevalence in large cohorts. Design: A cross-sectional analysis of baseline and prospectively collected cohort data. Participants: UK Biobank (UKBB) participants of genetically determined European ancestry (n = 438 711). Replication analyses were performed using clinical and genotyping data collected from European participants recruited to the Canadian Longitudinal Study of Aging (CLSA; n = 18 199), the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG; n = 1970), and the Blue Mountains Eye Study (BMES; n = 2440). Methods: Apolipoprotein E alleles and genotypes were determined, and their distributions were compared on the basis of glaucoma status. Similar analyses were performed using positive control outcomes associated with the APOE E4 allele (death, dementia, age-related macular degeneration) and negative control outcomes not associated with the APOE E4 allele (cataract, diabetic eye disease). Outcome phenotypes were also correlated with Alzheimer's dementia (AD), a clinical outcome highly associated with the APOE E4 allele. Main Outcome Measures: Results of APOE E4 genotype-phenotype comparisons were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Replication analyses investigated APOE E4 associations in 2 replication cohorts (CLSA and ANZRAG/BMES). Results: The APOE E4 allele was inversely associated with glaucoma (OR, 0.96; 95% CI, 0.93-0.99; P = 0.016) and both negative controls (cataract: OR, 0.98; 95% CI, 0.96-0.99; P = 0.015; diabetic eye disease: OR, 0.92; 95% CI, 0.87-0.97; P = 0.003) in the UKBB cohort. A paradoxical positive association was observed between AD and both glaucoma (OR, 1.30; 95% CI, 1.08-1.54; P < 0.01) and cataract (OR, 1.15; 1.04-1.28; P = 0.018). No association between the APOE E4 allele and glaucoma was observed in either replication cohort (CLSA: OR, 1.03; 95% CI, 0.89-1.19; P = 0.66; ANZRAG/BMES: OR, 0.97; 95% CI, 0.84-1.12; P = 0.65). Conclusions: A small negative association observed between APOE E4 and glaucoma within the UKBB was not evident in either replication cohort and may represent an artifact of glaucoma underdiagnosis in APOE E4 carriers. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Blood pressure variability and structural brain changes: a systematic review.

BACKGROUND: Blood pressure variability (BPV) has been linked with cognitive impairment and dementia. However, the pathophysiological mechanisms by which BPV affects cognition are unclear. This systematic review aims to assess the links between different BPV measures and white and grey matter structures. METHODS AND RESULTS: The following databases were searched from inception through to January 2021; EMBASE, MEDLINE, EMCARE and SCOPUS. Studies that reported on the relationship between within-individual BPV (short, medium or long-term variability) or a circadian blood pressure (BP) measurement and MRI assessed brain structures were included. Overall, 20 studies met the criteria and were included, of which 11 studies looked at short-term BPV, eight articles investigated visit-to-visit BPV and one study looked at a compositional BPV measurement. Due to heterogeneity in study samples, meta-analysis was not possible. Across the included studies, associations between MRI indices and BP dipping patterns were mixed; higher long-term BPV and higher sleep systolic BPV was found to be associated with lower whole brain volume and hippocampal volume. CONCLUSION: Increased BPV, in particular systolic long-term and systolic night-time BPV, appears to be associated with lower brain volume and hippocampal volume. This highlights the adverse effect that increased BPV has upon the brain, potentially contributing to cognitive decline, including dementia, in late-life.

How many geriatricians should, at minimum, be staffing health regions in Australia?

In any particular region, determining an adequate, quantifiable geriatrician full-time equivalent required to run geriatric medicine services comprehensively - that is spanning both inpatient and outpatient settings - remains an imperfect science. Whilst workforce planning may be addressed through 'demand versus supply' simulations, 'specialist-to-patient ratios' (SPRs) may be a useful additional workforce metric. There has never been a yardstick SPR, which 'defines' a satisfactory level of geriatrician manpower in any particular Australian hospital catchment. Here, a new methodology is proposed (tailored specifically to Australian geriatrics), illustrating how we may begin to transparently deduce such a national benchmark SPR. Allowing for some empiricism, the method presently favours an SPR approximating '0.4 full-time equivalent of geriatrician time per 10 000 head of population' in regions with 'average' population age distribution; this level of manpower may afford specialist assessment of targeted patients (widely capturing geriatric cases from acute to community settings). Further discussion on workforce planning methodologies is warranted.