Neuropsychiatric Symptoms and Neuropathological diagnoses of Alzheimer’s Disease and Related Dementias

Abstract

AbstractBackgroundThe associations of Alzheimer’s disease (AD) and related dementias (ADRD) pathologies with common neuropsychiatric symptoms (NPS) is not well‐established.MethodThis retrospective cohort study used 1,808 brains from 39 sites in the National Alzheimer’s Coordinating Center (NACC) V.10 collection for participants with the Neuropsychiatric Interview‐Questionnaire (NPI‐Q) administered annually and without consideration of clinical diagnosis. Brain autopsy diagnoses of AD, Lewy Body Disease (LBD), cerebral amyloid angiopathy, frontotemporal lobar degeneration (FTLD), cerebrovascular disease (CVD), hippocampal sclerosis, and “no known pathology” were examined. NPI‐Q domain score if present at any timepoint was the primary outcome and average NPI‐Q domain score during follow‐up was secondary. The associations of ADRD diagnoses with twelve NPI‐Q symptom domains were examined in regression analyses, correcting for multiple comparisons.ResultThe study sample of 1,808 adults had a mean [SD] age 80.0 [11.0] years and 54.6% were male. Apathy was the most prevalent NPS, reaching 80% in hippocampal sclerosis. CVD showed few NPS associations. FTLD was associated with increased apathy, increased disinhibition, and decreased psychosis and agitation compared to AD. Hippocampal sclerosis was associated with increased apathy (OR 2.60, 95%CI 1.86‐3.66, pfdr<.05) and disinhibition (OR 2.15, 95% CI 1.63‐2.84, pfdr<.05). In multiple regression analyses that included concomitant neuropathologies, the main findings remained. More severe pathology was associated consistently with increased NPS, e.g., LBD showed increase in hallucinations from brainstem (β=0.23, 95% CI 0.07‐0.76, p<.05) to limbic (β=1.69, 95% CI 1.27‐2.27, p<.01) to neocortical (β=4.49, 95% CI 3.27‐6.16, p<.001) pathology. Hallucinations were more common in participants with AD+LBD (168/534=31.5%) compared to AD without LBD (152/704=21.6%) and LBD without AD (23/119=19.6%).ConclusionVisual hallucinations may characterize LBD with AD more than LBD without AD. NPS criteria of apathy and disinhibition in behavioral variant frontotemporal lobar degeneration were supported. In hippocampal sclerosis, the novel findings of increased apathy and disinhibition merit further investigation. Severity of neuropathology was related to NPS severity, indicating that NPS reflect underlying ADRD pathology and highlight the importance of diagnosing and treating NPS.