The Effect of Multidomain Interventions on Global Cognition, Symptoms of Depression and Apathy - A Pooled Analysis of Two Randomized Controlled Trials.

BACKGROUND: Cardiovascular risk factors and lifestyle factors are associated with an increased risk of cognitive decline and dementia in observational studies, and have been targeted by multidomain interventions. OBJECTIVES: We pooled individual participant data from two multi-domain intervention trials on cognitive function and symptoms of depression to increase power and facilitate subgroup analyses. DESIGN: Pooled analysis of individual participant data. SETTING: Prevention of Dementia by Intensive Vascular Care trial (preDIVA) and Multidomain Alzheimer Preventive Trial (MAPT). PARTICIPANTS: Community-dwelling individuals, free from dementia at baseline. INTERVENTION: Multidomain interventions focused on cardiovascular and lifestyle related risk factors. MEASUREMENTS: Data on cognitive functioning, depressive symptoms and apathy were collected at baseline, 2 years and 3-4 years of follow-up as available per study. We analyzed crude scores with linear mixed models for overall cognitive function (Mini Mental State Examination [MMSE]), and symptoms of depression and apathy (15-item Geriatric Depression Scale). Prespecified subgroup analyses were performed for sex, educational level, baseline MMSE <26, history of hypertension, and history of stroke, myocardial infarction and/or diabetes mellitus. RESULTS: We included 4162 individuals (median age 74 years, IQR 72, 76) with a median follow-up duration of 3.7 years (IQR 3.0 to 4.1 years). No differences between intervention and control groups were observed on change in cognitive functioning scores and symptoms of depression and apathy scores in the pooled study population. The MMSE declined less in the intervention groups in those with MMSE <26 at baseline (N=250; MD: 0.84; 95%CI: 0.15 to 1.54; p<0.001). CONCLUSIONS: We found no conclusive evidence that multidomain interventions reduce the risk of global cognitive decline, symptoms of depression or apathy in a mixed older population. Our results suggest that these interventions may be more effective in those with lower baseline cognitive functioning. Extended follow-up for dementia occurrence is important to inform on the potential long-term effects of multidomain interventions

Neuroscience of apathy and anhedonia: a transdiagnostic approach

Apathy and anhedonia are common syndromes of motivation that are associated with a wide range of brain disorders and have no established therapies. Research using animal models suggests that a useful framework for understanding motivated behaviour lies in effort-based decision making for reward. The neurobiological mechanisms underpinning such decisions have now begun to be determined in individuals with apathy or anhedonia, providing an important foundation for developing new treatments. The findings suggest that there might be some shared mechanisms between both syndromes. A transdiagnostic approach that cuts across traditional disease boundaries provides a potentially useful means for understanding these conditions