Apathy as a Risky Neuropsychiatric Syndrome of Progression From Normal Aging to Mild Cognitive Impairment and Dementia: A Systematic Review and Meta-Analysis

Abstract

Background: Apathy has been suggested as a potential predictor of mild cognitive impairment (MCI) progression to dementia. Whether it might predict the transition from normal cognitive function to cognitive impairment has been less studied. The current study aimed to provide a comprehensive summary of the evidence on the association between apathy and the transition from normal cognitive function to cognitive impairment.Methods: We searched the PubMed, Embase, and Web of Science databases for longitudinal prospective cohort studies that evaluated apathy at baseline in the cognitively normal population and had cognitive impairment as the outcome. Random effects models were used, and heterogeneity was explored with stratification. The stability of the synthesized result was indicated using sensitivity analysis by excluding one study each time and recalculating the overall effect.Results: Ten studies comprising 26,195 participants were included. Apathy status was available for 22,101 participants. Apathy was present in 1,803 of 22,101 participants (8.16%). Follow-up ranged from 1 to 13 years. The combined odds ratio (OR) of cognitive impairment for patients with apathy was 2.07 (95% CI: 1.43–2.99; I2 = 86%), and the combined hazard ratio was 2.70 (95% CI: 1.38–5.27; I2 = 94%). The OR meta-analyses for different conversion outcomes were MCI (OR = 3.38, 95% CI: 1.57–7.28; I2 =71%), cognitive decline (OR = 1.27, 95% CI: 0.81–2.00; I2 = 64%) and dementia (OR = 2.12, 95% CI: 1.32–3.41; I2 = 86%). Subgroup analysis suggested that the association between apathy and cognitive impairment changed with age, depression adjustments, apathy measurement, and follow-up time.Conclusions: Apathy was associated with a greater than 2-fold increased risk of progression to cognitive impairment in the cognitively normal population. Future interventions targeting apathy management in the general population may reduce the risk of cognitive impairment.

Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment‐related aspects of apathy from depression in neurocognitive disorders

“…Both apathy and depression consistently predict an increased risk for the development of NCDs. A meta‐analysis of 10 studies that included over 22,000 individuals classified as cognitively normal found that apathy was associated with a 2‐fold increased risk of cognitive impairment 65 . Indeed, it has been suggested that apathy may be a pre‐dementia phenotype 16 .…”

Apathy and APOE in mild behavioral impairment, and risk for incident dementia

“…However, no previous work has operationalized apathy using the more conservative MBI classification approach, which offers greater specificity. A previous systematic review and meta‐analysis in NC revealed greater apathy‐associated rates of incident dementia, with a pooled HR of 3.42 from three included studies 21 . Similarly, in MCI, meta‐analysis demonstrated greater apathy‐associated rates of incident dementia, with a pooled HR of 1.54 from 11 included studies 22 .…”

“…A previous systematic review and meta‐analysis in NC revealed greater apathy‐associated rates of incident dementia, with a pooled HR of 3.42 from three included studies. 21 Similarly, in MCI, meta‐analysis demonstrated greater apathy‐associated rates of incident dementia, with a pooled HR of 1.54 from 11 included studies. 22 The relatively higher HR in NC versus MCI from these meta‐analyses is consistent with our findings, in which individuals with both NC and MCI were included, allowing for direct comparisons between cognitive groups.…”

Associations between apathy and comprehensive frailty as assessed by the Kihon Checklist among community‐dwelling Japanese older adults

“…In addition to physical frailty, apathy may impair cognitive function 10,44 and ADL 10 as well as reduce social support. 45 In the present study, individuals with apathy reported more frequent problems in IADL, oral function, and cognitive function compared to individuals without apathy.…”