Henry Brodaty

OBJECTIVES: To gain an understanding of elderly people's fear of falling by exploring the prevalence and determinants of perceived and physiological fall risk and to understand the role of disparities in perceived and physiological risk in the cause of falls. DESIGN: Prospective cohort study. SETTING: Community sample drawn from eastern Sydney, Australia. PARTICIPANTS: 500 men and women aged 70-90 years. MAIN OUTCOME MEASURES: Baseline assessment of medical, physiological, and neuropsychological measures, with physiological fall risk estimated with the physiological profile assessment, and perceived fall risk estimated with the falls efficacy scale international. Participants were followed up monthly for falls over one year. RESULTS: Multivariate logistic regression analyses showed that perceived and physiological fall risk were both independent predictors of future falls. Classification tree analysis was used to split the sample into four groups (vigorous, anxious, stoic, and aware) based on the disparity between physiological and perceived risk of falling. Perceived fall risk was congruent with physiological fall risk in the vigorous (144 (29%)) and aware (202 (40%)) groups. The anxious group (54 (11%)) had a low physiological risk but high perceived fall risk, which was related to depressive symptoms (P=0.029), neurotic personality traits (P=0.026), and decreased executive functioning (P=0.010). The stoic group (100 (20%)) had a high physiological risk but low perceived fall risk, which was protective for falling and mediated through a positive outlook on life (P=0.001) and maintained physical activity and community participation (P=0.048). CONCLUSION: Many elderly people underestimated or overestimated their risk of falling. Such disparities between perceived and physiological fall risk were primarily associated with psychological measures and strongly influenced the probability of falling. Measures of both physiological and perceived fall risk should be included in fall risk assessments to allow tailoring of interventions for preventing falls in elderly people.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.