Cognitive decline and health related quality of life in Alzheimer's disease

BACKGROUND Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease associated with significant disability and burden of care. In the absence of a cure for AD, effective interventions to optimize the health related quality of life (HRQoL) are required. Although the assessment and interpretation of HRQoL ratings are challenging, HRQoL has been recognized as a valuable outcome in AD research. However, knowledge regarding the clinically modifiable factors that drive changes in HRQoL is limited, so that rational evidence-driven interventions are lacking. The assumption that improvements of episodic memory, the prototypical deficit of AD, should lead to better HRQoL is yet to be demonstrated. The impact of progressive cognitive decline on the HRQoL of older adults with AD remains unclear. AIMS The body of this research consisted of five inter-related studies designed to address the following aims: Study 1: to determine (1) the agreement between community-dwelling people with mild to moderate AD and their family carers HRQoL ratings; (2) whether the instructed perspective of family carer-rated HRQoL (i.e. carer–carer perspective and carer–patient perspective) changes HRQoL outcomes; (3) the factors that independently contribute to self-reported and carer-reported HRQoL ratings (i.e. carer–carer perspective and carer– patient perspective); Study 2: to determine (4) whether self-reported and carer-reported HRQoL change over a period of 18 months; (5) the factors that mediate changes in HRQoL ratings by community-dwelling people with AD over a period of 18 months; (6) the factors that mediate changes in HRQoL ratings by family carers over a period of 18 months; Study 3: to determine (7) whether the underlying cognitive domains of people with AD remain stable over 18 months compared with controls free of dementia; (8) whether the associations between cognitive domains and carer and self-reported HRQoL ratings remain stable over 18 months; Study 4: to determine 9) whether the deterioration of specific cognitive functions commonly associated with AD predict which patients maintain or experience a deterioration of their HRQoL ratings over a period of 18 months. Study 5: as post-hoc analyses, to determine 10) the prevalence and association of exposure to potentially harmful medication with HRQoL. METHODS The research was designed as a longitudinal observational study. We recruited 80 community-dwelling older adults diagnosed with probable AD of mild or moderate severity (NINCDS-ADRD criteria) and their family carers, and 75 older adults without a diagnosis of dementia or MCI and their next-of-kin. The primary outcome of interest was HRQoL as measured by the Quality of Life-AD (QoL-AD) (by carer and by self). Specific cognitive functions were assessed with a broad range of well-established neuropsychological measures. Other explanatory variables included demographics, lifestyle, awareness, behavioural and psychological symptoms of dementia, burden-ofcare, use of medication, and functionality in daily life. Parametric and non-parametric bi-variate and multi-variate tests were used to test the study hypotheses. Depending on the number of planned comparisons, alpha was set at 1% or 5%.