Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Co-pathology in Alzheimer's disease and Lewy body disease and its association with neuropsychiatric symptoms.
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Gibson Lucy L, Grinberg Lea T, Paes Victor R, Mueller Christoph, Leite Renata E P, Nunes Paula Villela, Justo Alberto F O, Pasqualucci Carlos A, Ferriolli Eduardo, Aarsland Dag, Suemoto Claudia K
Аннотация
BACKGROUND: Mixed neuropathology is common in dementia, but the clinical implications for neuropsychiatric symptoms (NPSs) are not well characterized.
METHODS: In a population-based post mortem study, cases with Alzheimer's disease neuropathological change (ADNC) and Lewy body disease (LBD) were identified with any comorbid neuropathology (limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathological change (LATE-NC), cerebrovascular disease, LBD, and ADNC, respectively). Post mortem interviews collected information regarding NPSs and cognition to explore associations between each co-pathology and NPSs across the whole cohort, as well as in participants without dementia.
RESULTS: Co-existing neuropathology was frequent, even among individuals without clinical dementia. In cases with ADNC, comorbid neocortical LBD pathology was associated with hallucinations, regardless of cognitive status. However, ADNC co-pathology in LBD was linked to a greater NPS burden in the full cohort but not in individuals without dementia.
DISCUSSION: Lewy bodies are associated with hallucinations independent of cognitive impairment, whereas ADNC co-pathology may contribute to NPS only when widespread and associated with cognitive dysfunction.
HIGHLIGHTS: Neuropathological heterogeneity is high even in clinical stages without dementia. Neocortical but not limbic or brainstem LBD co-pathology is associated with hallucinations. LBs are associated with hallucinations independent of cognitive status. ADNC co-pathology is not associated with NPSs in LBD without dementia. LATE co-pathology is associated with increased risk of dementia but not NPS. Vascular co-pathology is associated with increased risk of delusions in ADNC.
METHODS: In a population-based post mortem study, cases with Alzheimer's disease neuropathological change (ADNC) and Lewy body disease (LBD) were identified with any comorbid neuropathology (limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathological change (LATE-NC), cerebrovascular disease, LBD, and ADNC, respectively). Post mortem interviews collected information regarding NPSs and cognition to explore associations between each co-pathology and NPSs across the whole cohort, as well as in participants without dementia.
RESULTS: Co-existing neuropathology was frequent, even among individuals without clinical dementia. In cases with ADNC, comorbid neocortical LBD pathology was associated with hallucinations, regardless of cognitive status. However, ADNC co-pathology in LBD was linked to a greater NPS burden in the full cohort but not in individuals without dementia.
DISCUSSION: Lewy bodies are associated with hallucinations independent of cognitive impairment, whereas ADNC co-pathology may contribute to NPS only when widespread and associated with cognitive dysfunction.
HIGHLIGHTS: Neuropathological heterogeneity is high even in clinical stages without dementia. Neocortical but not limbic or brainstem LBD co-pathology is associated with hallucinations. LBs are associated with hallucinations independent of cognitive status. ADNC co-pathology is not associated with NPSs in LBD without dementia. LATE co-pathology is associated with increased risk of dementia but not NPS. Vascular co-pathology is associated with increased risk of delusions in ADNC.