Kamath, Vidyulata

Aim Cognitive and behavioral phenomena define behavioral variant frontotemporal dementia (bvFTD), but neuropsychiatric symptoms (NPS) outside the core criteria are common throughout the illness. Identifying how NPS cluster in bvFTD may guide development of future therapies. Methods Participants ( n = 354) with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration Consortium. Dementia stage was defined as early (CDR® plus NACC FTLD ≤1) or advanced (CDR® plus NACC FTLD ≥1). Baseline and annual follow‐up visit data were analyzed to compare NPS across stages of bvFTD. Psychiatric states were captured using the Neuropsychiatric Inventory‐Questionnaire and Clinician Judgment of Symptoms. Polychoric cluster analysis was used to describe NPS clusters. Results NPS were highly prevalent (≥90%) in early and late bvFTD. Four NPS clusters were identified based on magnitude of factor loadings: affective, disinhibited, compulsive, and psychosis. Neuropsychiatric symptoms fluctuated across visits. In the affective cluster, depression showed the least visit‐to‐visit stability. In the disinhibited cluster, elation showed the least stability. Symptoms in the psychosis and compulsive clusters (hallucinations, delusions, obsessions/compulsions, and hyperorality) were largely stable, persisting from visit‐to‐visit in more than 50% of cases. Symptoms in the affective and disinhibited cluster were associated with the highest caregiver burden, while symptoms in the obsessive cluster were associated with the most functional impairment. Conclusion NPS in bvFTD are frequent and cluster into four discrete groups. The fluctuating nature of some NPS in bvFTD suggests that they may not be reliable markers of disease progression or stage.

Background: Olfactory identification (OI) impairment appears early in the course of Alzheimer’s disease dementia (AD), prior to detectable cognitive impairment. However, the neuroanatomical correlates of impaired OI in cognitively normal older adults (CN) and persons with mild cognitive impairment (MCI) are not fully understood. Objective: We examined the neuroanatomic correlates of OI impairment in older adults from the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Methods: Our sample included 1,600 older adults without dementia who completed clinical assessment and structural brain imaging from 2011 to 2013. We characterized OI impairment using the 12-item Sniffin’ Sticks odor identification test (score ≤6). We used voxel-based morphometry (VBM) and region of interest (ROI) analyses to examine the neuroanatomic correlates of impaired OI in CN and MCI, after adjusting for potential confounders. Analyses were also separately stratified by race and sex. Results: In CN, OI impairment was associated with smaller amygdala gray matter (GM) volume ( p < 0.05). In MCI, OI impairment was associated with smaller GM volumes of the olfactory cortex, amygdala, entorhinal cortex, hippocampus, and insula (ps < 0.05). Differential associations were observed by sex in MCI; OI impairment was associated with lower insular GM volumes among men but not among women (p-interaction = 0.04). There were no meaningful interactions by race. Conclusion: The brain regions associated with OI impairment in individuals without dementia are specifically those regions known to be the primary targets of AD pathogenic processes. These findings highlight the potential utility of olfactory assessment in the identification and stratification of older adults at risk for AD.