期刊
NEUROLOGY
卷 98, 期 14, 页码 E1422-E1433出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0000000000200001
关键词
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资金
- National Institute on Aging/NIH [U01 AG016976]
- National Institute on Aging [P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P50 AG047266, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P30 AG008017]
- The National Institute on Aging [P30 AG010161, P50 AG047366, P30 AG010129, P50 AG016573, P50 AG005131, P50 AG023501, P30 AG035982, P30 AG028383, P30 AG053760, P30 AG010124, P50 AG005133, P50 AG005142, P30 AG012300]
- 'National Institute on Aging' [P30 AG049638, P50 AG005136, P50 AG033514, P50 AG005681, P50 AG047270]
- [R01 AG061111]
- [RF1 NS118584]
- [R01AG057187]
- [R01AG054060]
- [UK-ADC P30AG028383]
Limbic-predominant age-related Tar DNA binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC) is strongly associated with cognitive impairment. This study found that LATE-NC patients with hippocampal sclerosis (HS) pathology may have worse cognitive status and more severe impairments in memory and orientation. Additionally, the presence of comorbid HS pathology is associated with more widespread TDP-43 proteinopathy and more severe non-beta-amyloid vessel wall pathologies.
Background and Objectives Limbic-predominant age-related Tar DNA binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC) is present in approximate to 25% of older persons' brains and is strongly associated with cognitive impairment. Hippocampal sclerosis (HS) pathology is often comorbid with LATE-NC, but the clinical and pathologic correlates of HS in LATE-NC are not well understood. Methods This retrospective autopsy cohort study used data derived from the National Alzheimer's Coordinating Center Neuropathology Data Set, which included neurologic status, medical histories, and neuropathologic results. All autopsies were performed in 2014 or later. Among participants with LATE-NC, those who also had HS pathology were compared with those without HS with regard to candidate risk factors or common underlying diseases. Statistical significance was set at nominal p < 0.05 in this exploratory study. Results A total of 408 participants were included (n = 221 were LATE-NC+/HS-, n = 145 were LATE-NC+/HS+, and n = 42 were LATE-NC-/HS+). Most of the included LATE-NC+ participants were severely impaired cognitively (83.3% with dementia). Compared to HS- participants, LATE-NC+ participants with HS trended toward having worse cognitive status and scored lower on the Personal Care and Orientation domains (both p = 0.03). Among LATE-NC+ participants with Braak neurofibrillary tangle (NFT) stages 0 to IV (n = 88), HS+ participants were more impaired in the Memory and Orientation domains (both p = 0.02). There were no differences (HS+ compared with HS-) in the proportion with clinical histories of seizures, stroke, cardiac bypass procedures, diabetes, or hypertension. The HS+ group lacking TDP-43 proteinopathy (n = 42) was relatively likely to have had strokes (p = 0.03). When LATE-NC+ participants with or without HS were compared, there were no differences in Alzheimer disease neuropathologies (Thal beta-amyloid phases or Braak NFT stages) or Lewy body pathologies. However, the HS+ group was less likely to have amygdala-restricted TDP-43 proteinopathy (LATE-NC stage 1) and more likely to have neocortical TDP-43 proteinopathy (LATE-NC stage 3) (p < 0.001). LATE-NC+ brains with HS also tended to have more severe circle of Willis atherosclerosis and arteriolosclerosis pathologies. Discussion In this cohort skewed toward participants with severe dementia, LATE-NC+ HS pathology was not associated with seizures or with Alzheimer-type pathologies. Rather, the presence of comorbid HS pathology was associated with more widespread TDP-43 proteinopathy and with more severe non-beta-amyloid vessel wall pathologies.
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