Mild behavioral impairment associates with Alzheimer’s disease biomarkers and greater risk of incident dementia in patients with MCI

Abstract

AbstractBackgroundMild behavioral impairment (MBI) is characterized by later life onset of sustained neuropsychiatric symptoms (NPS) as an at‐risk state for incident cognitive decline and dementia. Here we assess differences in sustained NPS versus transient NPS versus no NPS, on neuroimaging markers and cognitive scores, and the risk of progression to dementia.MethodData from 764 individuals with MCI from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed. NPI‐Q items were transformed to MBI domains using a published algorithm. MBI requires sustained NPS for 6 months, thus we grouped individuals based on two visits 6‐months apart as sustained (present at both visits, n=258), transient (present at one visit, n=346), and no NPS (present at neither visit, n=160). For the cross‐sectional analyses, outcomes of interest were matched to the clinical visits assessing NPS. We investigated differences in brain metabolic activity by [18F] fluorodeoxyglucose (FDG)‐PET, and composite scores of executive functioning and memory in these groups using multiple linear regression adjusted for age, sex and education. Time‐varying cox regression models were constructed, adjusting for age, sex, and education to assess if time to dementia is associated with MBI.ResultIn these participants with MCI, compared to individuals with no NPS, sustained NPS was associated with reduced [18F] FDG uptake [Adjusted‐=‐0.06 (SE=0.02); p value=0.003], lower executive functioning scores [Adjusted‐=‐0.28 (SE=0.08); p value=0.001], and memory impairment [Adjusted‐=‐0.38 (SE=0.08); p value=<.001]. Compared to individuals with transient NPS, sustained NPS was also associated with reduced glucose metabolism [Adjusted‐=‐0.03 (SE=0.01); p value=0.018], and lower memory scores [Adjusted‐=‐0.17 (SE=0.06); p value=0.007], but not executive functioning. Compared to no or transient NPS, the risk for incident dementia was highest in the sustained NPS group (HR 1.87, 95% CI 1.50 to 2.34).ConclusionIn a cohort of individuals with MCI, baseline NPS are associated with biomarkers of dementia risk and predict progression to dementia. MBI, as operationalized here by sustained NPS, was associated with worse memory, lower glucose metabolism, and higher risk of incident dementia compared to transient NPS. There is diagnostic and prognostic utility in determining if NPS are sustained or transient, further validating the MBI construct.