The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease

Abstract

Objectives: Individuals with mild cognitive impairment (MCI) are at high risk of developing dementia and/or Alzheimer disease (AD). Among persons with MCI, depression and anxiety have been associated with an increased risk of incident dementia. We examined whether neuropsychiatric symptoms in MCI increased the risk of incident dementia (all-cause) and incident AD.

Design: Longitudinal cohort study followed annually (median: 1.58 years).

Setting: National Alzheimer's Coordinating Center database combining clinical data from 29 Alzheimer's Disease Centers.

Participants: A total of 1,821 participants with MCI.

Measurements: 1) Progression to dementia (all-cause) or AD, 2) Neuropsychiatric Inventory Questionnaire (NPI-Q), 3) Geriatric Depression Scale (GDS), 4) Clinical Dementia Rating Global Score and Sum of Boxes, and 5) Mini-Mental State Examination (MMSE). The association of covariates with risk of incident dementia or AD was evaluated with hazard ratios (HR) determined by Cox proportional-hazards models adjusted for age, ethnicity, Clinical Dementia Rating Global Score and Sum of Boxes, and MMSE.

Results: A total of 527 participants (28.9%) progressed to dementia and 454 (24.9%) to AD. Baseline GDS > 0 was associated with an increased risk of incident dementia (HR: 1.47, 95% CI: 1.17-1.84) and AD (HR: 1.45, 95% CI: 1.14-1.83). Baseline NPI > 0 was associated with an increased risk of incident dementia (HR: 1.37, 95% CI: 1.12-1.66) and AD (HR: 1.35, 95% CI: 1.09-1.66).

Conclusions: Neuropsychiatric symptoms in MCI are associated with significantly an increased risk of incident dementia and AD. Neuropsychiatric symptoms may be among the earliest symptoms of preclinical stages of AD and targeting them therapeutically might delay transition to dementia.

FIGURE 1. RISK OF INCIDENT DEMENTIA STRATIFIED BY PRESENCE/ABSENCE OF NPI SYMPTOMS AT BASELINE

Kaplan-Meier survival curves for risk of incident dementia in the 1821 MCI participants with at least one follow-up are displayed, stratified by baseline NPI=0 vs. NPI>=1. Statistics are reported in Table 3.