Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

Abstract

We examined the relationships between Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular brain injury (VBI) in 2 large autopsy samples. Because findings may differ between study populations, data came from U.S. Alzheimer's Disease Centers contributing to the National Alzheimer's Coordinating Center (n = 2742) and from the population-based Adult Changes in Thought study (n = 499). Regardless of study population, over 50% of participants with ADNC had co-occurring LBD or VBI; the majority of whom had a clinical AD dementia diagnosis prior to death. Overlap of pathologies was similar between studies, especially after standardizing to the distribution of age and dementia status in the Adult Changes in Thought population. LBD, but not VBI, was positively associated with ADNC in both studies. Interestingly, cortical LBD was more common in those with intermediate ADNC compared to low or high ADNC, especially in the National Alzheimer's Coordinating Center (p < 0.001). High prevalence of co-occurring neuropathologies among older adults with dementia has implications for accurate diagnosis of dementia etiologies and development of disease-modifying strategies.

Keywords: Alzheimer's disease; Lewy body disease; Mixed neuropathologies; Older adults; Vascular brain injury.

Figure 1. Co-occurrence of Alzheimer’s disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular brain injury (VBI) stratified by age

ACT, Adult Changes in Thought study; NACC, National Alzheimer’s Coordinating Center. ADNC = moderate/frequent neuritic plaques & Braak stage III–VI; LBD = Lewy bodies in any brain region examined; VBI = gross infarcts and cortical microinfarcts. Note: 191 NACC participants with age of death less than 65 years were excluded.

Figure 2. Prevalence (percent) of Alzheimer’s disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular brain injury (VBI) standardized to ACT overall study population

Prevalence estimates (percent) standardized to the distribution of age (<80yrs, 80–90 years, and 90+) and dementia status (demented, non-demented) at last visit among all ACT participants (autopsied and non-autopsied). Confidence intervals for estimates shown in Table 4. ACT, Adult Changes in Thought study; NACC, National Alzheimer’s Coordinating Center. ADNC = moderate/frequent neuritic plaques & Braak stage III–VI; LBD = Lewy bodies in any brain region examined; VBI = gross infarcts and cortical microinfarcts.

Figure 3. Prevalence of Lewy body disease (LBD) subtypes in participants with low, intermediate, and high Alzheimer’s disease neuropathologic change (ADNC)

ACT, Adult Changes in Thought study; NACC, National Alzheimer’s Coordinating Center. Low ADNC= no/sparse CERAD neuritic plaques & any Braak stage OR any neuritic plaques & Braak stage 0-II; intermediate ADNC= moderate/frequent neuritic plaques & Braak stage III–IV; high ADNC = moderate/frequent neuritic plaques & Braak stages V–VI. *p<0.001 for difference in prevalence of LBD subtype by level of ADNC based on χ2 (NACC) or Fisher’s exact test (ACT).

Figure 4. Prevalence of vascular brain injury (VBI) in participants with low, intermediate, and high Alzheimer’s disease neuropathologic change (ADNC)

ACT, Adult Changes in Thought study; PANDA ADCs, Pacific Northwest Dementia and Aging Neuropathology Group Alzheimer’s Disease Centers (Oregon Health & Science University and University of Washington). Low ADNC = no/sparse CERAD neuritic plaques & any Braak stage OR any neuritic plaques & Braak stage 0-II; Intermediate ADNC = moderate/frequent neuritic plaques & Braak stage III–IV; High ADNC = moderate/frequent neuritic plaques & Braak stages V–VI. *p<0.05 for difference in prevalence of VBI by level of ADNC based on fisher’s exact test.