Risk factors for apathy in Alzheimer's disease: A systematic review of longitudinal evidence.

BACKGROUND

Apathy is frequent and persistent in Alzheimer's disease (AD), associated with poor prognosis and carer distress; yet our knowledge of risk factors remains limited.

AIMS: To identify risk factors associated with apathy incidence and progression in AD over time.

METHODS

We systematically reviewed evidence based on longitudinal studies assessing risk factors for apathy in AD up to June 2021. Two authors independently assessed article eligibility and rated quality.

RESULTS

13,280 articles were screened, of which 13 met inclusion criteria. Studies had a mean follow-up of 2.7 years reporting on a total of 2012 participants. Most findings were based on single studies of moderate quality evidence. Risk factors increasing apathy onset were: being a carrier of the T allele of the PRND gene polymorphism, and having high levels of the IL-6 and TNFα cytokines at baseline. Risk factors for apathy worsening were: reduced inferior-temporal cortical thickness, taking antidepressants, being an ApoE ε4 carrier, living longer with AD, lower cognitive test scores, higher baseline apathy, premorbid personality traits (lower agreeableness, higher neuroticism), and higher midlife motivational abilities.

CONCLUSIONS

Although results are limited by the small number of studies, this review identified specific genetic, neurobiological, AD specific, and dispositional factors that may increase risk of apathy onset and worsening in AD.