de Oliveira_2015_J.Neurol.Sci_359_127

Midlife cerebrovascular risk, low cognitive reserve and APOE4+ haplotypes are risk factors for Alzheimer's disease dementia (AD). We prospectively searched for factors that might be associated with yearly changes in caregiver burden, cognition, basic and instrumental functionality in 193 consecutive outpatients with late-onset AD, namely gender, APOE haplotypes, schooling, age at AD onset, marital status, depression, cerebrovascular risk factors, serum TSH levels, cognitive and physical activities, and treatment with cholinesterase inhibitors or anti-psychotics, while also investigating associations between APOE haplotypes and patient participation in cognitive or physical activities. Higher education led to greater declines in instrumental functionality, whereas increases in body mass index were associated with rises in basic functionality and cognitive test scores. Established cerebrovascular risk factors had no independent effects over cognitive or functional change, but their combinations led to cognitive improvement, possibly related to enhanced cerebral perfusion in late life. Cholinesterase inhibitors improved caregiver burden. Enhanced instrumental functionality and steeper cognitive decline by the use of anti-psychotics might be attributed to improved behavioural symptoms and neuropsychiatric side effects, respectively. Each copy of APOE-epsilon4 (beta=-0.102) led to cumulative decreased participation in physical activities (rho=0.015). These results might impact public health policies and the interpretation of clinical trials for AD.