Background: Mild behavioral impairment (MBI) refers to the de novo emergence of persistent neuropsychiatric symptoms in older adults and has been associated with cognitive decline and incident dementia. The purpose of this study was to identify the structural neural correlates of MBI using a hypothesis-driven region-of-interest (ROI) approach. Method:The study cohort consisted of 744 participants (60.3% female; mean and SD of age = 71.0 ± 9.7 years; mean and SD of education: 15.8 ± 5.3 years) without dementia from the National Alzheimer's Coordinating Centre dataset. Structural T1weighted images for each participant were processed and segmented using FreeSurfer and then normalized by age, sex, intracranial volume, scanner characteristics, and image quality to generate adjusted measures of grey matter volume (GMV) for each ROI. Our primary ROIs included five regions, each representing one Braak stage: entorhinal cortex (stage I), hippocampus (stage II), fusiform gyrus (stage III), inferior temporal cortex (stage IV), and frontal pole (stage V). We also included three hippocampal subfields (CA1, CA3, CA4) and four ROIs commonly associated with various psychiatric disorders (amygdala, insula, anterior cingulate, prefrontal cortex) as a secondary analysis. All ROIs are anatomically highlighted in Figure 1. Participants were classified as MBI+ if they presented with MBI symptoms derived from the Neuropsychiatric Inventory Questionnaire for two consecutive visits one year apart. Logistic regressions adjusting for cognitive diagnosis (cognitively normal, n = 568; mild cognitive impairment, n = 176) were used to model the relationship between ROI GMV (predictor) and MBI status (outcome).Result: As shown in Table 1, lower GMV in early Braak stage ROIs (entorhinal cortex and hippocampus) was associated with MBI+ status. This trend was maintained for all hippocampal subfield ROIs. However, mid-late Braak stage ROI (fusiform gyrus, inferior temporal cortex, frontal pole) GMVs were not associated with MBI status. For psychiatric disorder ROIs, lower GMV in only the amygdala was associated with MBI+ status.
Background: Depressive symptoms in older adults are important predictors of incident dementia. Symptoms can be assessed in several ways, including self-reported or informant-reported measures. It is unclear whether one is superior in predicting dementia onset or how to interpret discordant reports. Here, in a large sample of nondementia older adults for whom depressive symptoms were assessed via both selfreport and informant-report, we test independent and divergent prognostic utility for dementia.Method: Data from 10,684 non-dementia subjects from the National Alzheimer's Coordinating Centre were analysed. This included individuals with normal cognition (NC; CDR=0) and Mild Cognitive Impairment (MCI; CDR=0.5). Geriatric Depression Scale-15 (GDS) was used for self-report and the Neuropsychiatric Inventory Questionnaire depression item (NPI-Q-D) was used for informant-report. Cox regression and Kaplan Meier (KM) survival analyses were used to explore the measures as independent predictors of dementia, and the putative interaction between them. Outcome was defined as change to CDR≥1 at follow-up. The cox model was adjusted for age, sex, and education. CDR category was included to determine applicability of findings across cognitive categories. GDS-15 and NPI-Q-D scores were added as continuous predictors. For the KM analysis, depressive symptoms were dichotomized as GDS+/GDSand NPI-Q-D+/NPI-Q-D-using cut-off scores of ≥5 for GDS-15 and ≥2 for NPI-Q-Depression.
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