PRE-DIAGNOSTIC MANIFESTATIONS OF ALZHEIMER’S DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF LONGITUDINAL STUDIES

Abstract

AbstractAlzheimer’s disease (AD) is associated with a range of non-cognitive symptoms that can be early or even presenting features. Better recognition of pre-diagnostic symptoms of AD would support improved early detection and diagnosis.To identify possible prodromal symptoms of AD, we systematically searched electronic databases for prospective longitudinal studies to March 2023, that reported the risk of AD diagnosis associated with non-cognitive symptoms. We conducted random-effects meta-analyses to obtain pooled odds of subsequent AD.Thirty studies met eligibility criteria. Most studies (n=18) reported on the association of depression with subsequent AD diagnosis (pooled OR= 1.80; 95% CI: 1.29 to 2.50; I2=95.8%). Hearing loss, weight loss, spondylosis and hypotension also predicted a subsequent AD diagnosis.This evidence suggests that these features that may be recorded during routine healthcare encounters are risk markers for incident AD and could therefore support improved early detection and diagnosis.