The evolution of neuropsychiatric symptoms in atypical variants of Alzheimer’s disease

Abstract

AbstractBackgroundNeuropsychiatric symptoms (NPS) constitute a pervasive component of Alzheimer’s disease (AD) for patients with a “typical” (i.e. amnestic‐predominant) phenotype. The prevalence and course of NPS is largely unknown in patients with atypical variants of AD and the few conducted studies are clouded by inclusion of Aβ‐negative individuals. Understanding the evolution of NPS in atypical AD is crucial for adequate patient care for individuals with these rare and early‐onset AD phenotypes.MethodsWe included 632 amyloid‐β‐positive subjects from the Amsterdam Dementia Cohort, including 26 behavioral variant AD (bvAD; showing ≥2/6 behavioral variant frontotemporal dementia (bvFTD) criteria), 30 logopenic variant primary progressive aphasia (lvPPA), 75 posterior cortical atrophy (PCA; Table 1). In addition, we included 47 AD patients with isolated predominant amnestic profiles (“amnestic AD”) and 454 amyloid‐β‐positive AD patients without predominant weaknesses on a single domain as “typical AD” reference groups. Linear mixed models were performed to compare baseline and longitudinal change in NPS as measured using Neuropsychiatric Inventory (NPI) scores across groups using general AD as the reference group (average follow‐up NPI assessment: 1.8 years).ResultAt baseline, apathy, appetite changes, disinhibition, aberrant motor behavior, and agitation were most frequent in bvAD patients, showing higher levels than typical AD (Figure 1). Apathy, irritability, anxiety, depression and appetite changes occured most frequently in PCA patients with similar levels as typical AD groups, whereas patients with lvPPA showed lower frequencies on 11/12 NPS compared to typical AD. Linear mixed models showed a significant decrease in total NPI score over time for the bvAD group (β(SE) = ‐0.0067 (0.003), p<.05). No significant changes were found in the other groups (all p>.05, Figure 2).ConclusionThis study assessing the baseline magnitude and longitudinal progression of NPS across amyloid‐positive clinical variants of AD suggests that patients with PCA do not show increased NPS, whereas patients with lvPPA show less NPS than typical AD patients. Despite high baseline levels of NPS in bvAD, NPS decrease over time, corresponding to observations in patients with bvFTD and suggestive of an inverted U‐shape trajectory of NPS in these patients.