Associations Between Neuropsychiatric Symptom Burden, Change in Cognitive Status and Survival in Autopsy-confirmed Cohorts of Lewy Body Disease and Alzheimer’s Disease
Shannon Chiu1, Cecilia Tremblay3, Nan Zhang2, Charles Adler1, Holly Shill5, Shyamal Mehta6, Erika Driver-Dunckley1, David Shprecher4, Christine Belden3, Geidy Serrano3, Thomas Beach3, Alireza Atri3, Parichita Choudhury4
1Neurology, Mayo Clinic Arizona, 2Mayo Clinic Arizona, 3Banner Sun Health Research Institute, 4Neurology, Banner Sun Health Research Institute, 5Neurology, Barrow Neurology Clinics, 6Neurology, Mayo Clinic, Arizona
Objective:
To investigate the impact of neuropsychiatric symptom (NPS) burden and cognitive status on survival in pathological cohorts of Lewy body disease (LBD) and Alzheimer’s disease (AD)
Background:
Presence of pathological LBD is typically associated with higher NPS burden and poorer survival. Predictors of mortality at dementia diagnosis include age, more depression and worse cognitive status. Predictors of survival during early cognitive changes and relationship to final pathological burden is unknown.
Design/Methods:
We included 313 initially non-demented cases from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with longitudinal Neuropsychiatric Inventory-Questionnaire (NPI-Q) scores who came to autopsy (mean follow-up duration 6±4 years). Participants were categorized by final Unified Staging System for Lewy Body Disorders (USSLB) (stage-I [n=9], IIA-B [n=32, 16], III [n=59], IV [n=70]); 127 cases had USSLB stage-0, including AD without LB (n=66). We performed Cox regression analyses, adjusting for cognitive status change, age, sex, motor subscale of Unified Parkinson's Disease Rating Scale (UPDRS-III), and Functional Assessment Scale (FAS) from the National Alzheimer’s Coordinating Center.
Results:
Individuals with USSLB stages III-IV were younger at first NPI-Q (mean 79±7 years) and at death (mean 85±8 years) (p<0.05). UPDRS-III (mean 23±15) and frequency of mild cognitive impairment (MCI) status (37%) at first NPI-Q were highest for USSLB stage-IV (p<0.05). Total initial NPI-Q score was highest for USSLB stage-IIB (mean 3.6±3.4), followed by stage-IV (3.3±3.4) and III (2.9±3.7) (p<0.05). While nighttime behaviors were most frequent/severe in stage-IIB, hallucinations were most prominent in stage-IV (p<0.05). When analyzing survival across all cases irrespective of underlying pathology, higher first available total NPI-Q, progression to dementia, age and UPDRS-III at first NPI-Q were predictive of worse survival (p<0.05).
Conclusions:
Cognitive progression to dementia (not MCI), higher initial NPI-Q scores, older age, and poorer baseline motor function, were associated with worse survival across pathological cases of LBD and AD.
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