Neuropsychiatric Symptoms Associated With Frontotemporal Atrophy in Older Adults Without Dementia

Objectives: We investigated the association between neuropsychiatric symptoms (NPS) and frontotemporal atrophy (FTA) in older adults without dementia. We hypothesized that the odds of having NPS would be increased in the presence of FTA.

Methods: NACC participants ≥ 50 years old with available data on FTA were considered for eligibility. Those with a diagnosis of mild cognitive impairment (MCI) and those who were cognitively unimpaired (CU) were separately analyzed. NPS were quantified on the Neuropsychiatric Inventory Questionnaire. Binary logistic regression models estimated the association (odds ratios and 95% confidence intervals are provided) between FTA and having each of 11 NPS (psychotic symptoms were grouped together) in CU and MCI individuals.

Results: FTA data were available for 3165 participants with MCI and 4051 CU: 207 and 55 had FTA on structural MRI studies, respectively. In the MCI group, the presence of FTA was associated with higher odds of having elation [2.42(1.33-4.40), p = 0.004], aberrant motor behavior [2.43(1.61-3.69), p < 0.001], appetite disorders [2.15(1.52-3.04), p < 0.001], apathy [2.05(1.48-2.85), p < 0.001] and disinhibition [2.02(1.38-2.96), p < 0.001]. The odds of having specific NPS were not significantly elevated in CU individuals with FTA. Of note, the size and direction of the associations were indicative of a potential relationship between FTA and specific NPS (most notably elation, aberrant motor behavior, appetite disorders and anxiety); in light of the small number of CU individuals with FTA we believe this analysis was underpowered and obscured several true associations.

Conclusions: FTA was associated with higher odds of some NPS in older adults with MCI but not with normal cognition.