Skip to main content
 
Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
 

See our updated masking policy »

Stanford Health Care

Neuropathologic lesions and comorbidity in Alzheimer disease and related dementias in a heterogeneous clinical population. Alzheimer's & dementia : the journal of the Alzheimer's Association Godrich, D., Richeson, P., Schellenberg, G. D., Scott, W. K., Montine, T. J., Beecham, G. W. 1800; 17 Suppl 3: e056249

Abstract

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia. Upon autopsy, most dementia patients display the core AD brain lesions: neurofibrillary tangles (NFTs), neuritic plaques (NPs), and diffuse plaques (DPs). Often, patients display other non-AD lesions: Lewy bodies (LBs), cerebral amyloid angiopathy (CAA), arteriolosclerosis, hippocampal sclerosis (HS), and vascular brain injury (VBI). Previous population-based studies suggest that dementia of mixed pathologies is present common and associated with more severe cognitive impairment. Here, we report on the generalizability of these findings in a more heterogeneous clinic-based group and describe the contribution of individual lesions and lesion comorbidity to severity and progression of dementia.METHOD: We used the National Alzheimer's Coordinating Center (NACC) database, identifying 5,272 individuals with a neuropathology assessment. Both AD and non-AD lesions were scored as absent/mild, moderate, or severe. Individual lesion scores summed to construct a neuropathology composite score (NPCS). Individual lesions and NPCS were tested for association with neurocognitive and functional impairment using the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating sum of boxes (CDR-SOB), respectively, as endpoints in linear regression models. We also evaluated progression in 3,934 individuals with multiple visits using the NPCS and clinical outcomes in a longitudinal multilevel mixed model.RESULT: Individuals with mixed pathologies (AD plus non-AD) were more functionally and neurocognitively impaired than those with AD or non-AD lesions alone. Full models showed most lesions were significantly associated with cognitive function (p<0.05). NFTs, HS, and NPs showed the highest effect sizes while DPs and VBI showed the lowest. When modeling with NPCS, associations with MMSE and CDR-SOB were highly significant (p<2E-16). Finally, when controlling for sex and number of visits, NPCS was significantly associated with progression of cognitive decline (p < 0.0001).CONCLUSION: These data suggest that severity of lesions and lesion comorbidity are highly associated with dementia severity in the more heterogeneous clinic-based NACC dataset. These results (1) confirm the utility of neuropathological collections, (2) expand the generalizability of past findings to a clinic-based group, and (3) suggest that mixed-type pathologies are a major contributor to dementia.

View details for DOI 10.1002/alz.056249

View details for PubMedID 35109341