Late‐life emergence of neuropsychiatric symptoms and risk of cognitive impairment in cognitively unimpaired individuals

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INTRODUCTION: Neuropsychiatric symptoms (NPS) often precede cognitive impairment. We investigated the longitudinal relationship between emergent, significant NPS and cognitive decline in cognitively unimpaired older adults. We also assessed the combined effect of NPS and Alzheimer's disease (AD) biomarkers on subsequent cognitive impairment. METHODS: We included 190 cognitively unimpaired participants without NPS at baseline and tracked the emergence of significant NPS and conversion to mild cognitive impairment (MCI). RESULTS: The average follow-up was 8.1 years, with a maximum of 19 years. Participants with emergent, significant NPS had a 3.92-fold higher risk of cognitive impairment than those without (95% confidence interval 1.51-10.17, P = 0.005). Individuals with NPS and AD biomarkers showed a markedly higher conversion rate to MCI than those with neither risk factor. DISCUSSION: Our findings emphasize the role of emergent, significant NPS as early clinical indicators of cognitive impairment and suggest the potential benefit of incorporating clinical symptoms and neurobiological markers to better predict cognitive course. HIGHLIGHTS: We investigated the association between emergent neuropsychiatric symptoms (NPS) and conversion to mild cognitive impairment (MCI). One hundred ninety cognitively unimpaired individuals were followed for an average of 8.1 years. Emergent NPS increased the risk of conversion to MCI > 3-fold. After emergent NPS, cognitive test performance declined. The co-occurrence of NPS and high cerebrospinal fluid phosphorylated tau181 amplified the risk of MCI.

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