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Mild behavioral impairment associates with Alzheimer’s disease biomarkers and greater risk of incident dementia in patients with MCI
Author(s) -
Ismail Zahinoor,
Gill Sascha,
Wang Meng,
Naude James,
Smith Eric E.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044905
Subject(s) - dementia , neuroimaging , medicine , proportional hazards model , cognitive impairment , disease , cognitive decline , cognition , alzheimer's disease neuroimaging initiative , memory impairment , alzheimer's disease , oncology , clinical psychology , psychology , psychiatry
Background Mild 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. Method Data 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 [ 18 F] 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. Result In these participants with MCI, compared to individuals with no NPS, sustained NPS was associated with reduced [ 18 F] 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). Conclusion In 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.