DOI: 10.1002/alz.079470 ISSN: 1552-5260

Associations between neuropsychiatric symptoms, pathology in neuropathological cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies

Cécilia Tremblay, Neha Shakir, Nan Zhang, Charles Adler, Christine Belden, Shyamal Mehta, Holly Shill, Erika Driver‐Dunckley, Thomas G Beach, Geidy E Serrano, Alireza Atri, Parichita Choudhury
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Neuropsychiatric symptoms (NPS) are frequent in Alzheimer’s Disease dementia (ADD) but a higher NPS burden is found in dementia with Lewy bodies (DLB). Lewy body (LB) pathology frequently co‐occurs with AD pathology and may not meet neuropathological criteria for DLB (ADLB). Previous studies have shown that both ADLB and DLB cases have faster cognitive and/or functional decline compared to AD. However, the differences in NPS severity over disease course and survival in these pathologic subgroups is not well understood.


Cases from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with a final neuropathologic diagnosis of DLB (±AD co‐pathology; n = 65), ADLB (n = 89), AD (without LB) (n = 140), and controls (no neuropathological diagnosis) (n = 82) were included. Total NPI‐Q (scores ranging from 0‐36) at time of enrollment and within 2.5 years of death were calculated for all groups. Statistical analysis utilizing ANCOVA (adjusting for age, sex, baseline MMSE and cognitive symptom duration) with pairwise comparisons, and Kaplan‐Meier curves were completed.


Age at onset of cognitive symptoms was not different between pathology groups. NPI‐Q scores at enrollment were highest in ADLB (7.33 ± 4.85), and higher (p<0.001) than DLB (5.10 ± 3.37), AD (4.54 ± 3.63) and controls (1.78 ± 1.70). At final evaluation, NPI‐Q scores were highest in DLB (10.04 ± 6.28), followed by ADLB (8.0 ± 4.), and ADD (7.61 ± 5.05) when compared to controls (2.78 ± 3.97) (all p<0.001). DLB and AD demonstrated significant increases in NPI‐Q severity during follow up (p < 0.001). AD had longer survival time (5.8 years) compared to ADLB (4.0 years) and DLB (3.9 years). Subjects with NPS had a shorter median survival time (3.4 years) compared to subjects without NPS (6.5 years; p = 0.002).


A higher NPS burden and shorter survival is seen in both DLB and ADLB, as compared with AD. This suggests that diffuse neocortical LB pathology is not the major driver of either NPS or survival.

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