TY - JOUR
T1 - Hippocampal sclerosis in the elderly
T2 - Genetic and pathologic findings, some mimicking Alzheimer disease clinically
AU - Pao, Winnie C.
AU - Dickson, Dennis W.
AU - Crook, Julia E.
AU - Finch, Nicole A.
AU - Rademakers, Rosa
AU - Graff-Radford, Neill R.
PY - 2011/10
Y1 - 2011/10
N2 - Background: Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration. Methods: We studied the clinical and pathologic features of HpScl in 205 consecutive patients with dementia who came to autopsy from 1997 to 2008, focusing on associations with TAR DNA-binding protein 43 (TDP-43) pathology and allelic variants in the progranulin (GRN) and apolipoprotein E (APOE). RESULTS: Of the 205 dementia patients, 28 had HpScl (14%). TDP-43 pathology was more frequent in cases with HpScl compared with those without HpScl (89% vs. 24%). GRN rs5848 T-allele but not APOE ε4 was associated with HpScl. In cases of HpScl with TDP-43 pathology and age of onset after 75 years (n=11), 8 had Alzheimer disease (AD)-like amnestic syndrome, but most (6 of 8) had pathology not consistent with AD (Braak stage III or less), including 4 with frontotemporal lobar degeneration with TDP, 1 with diffuse Lewy body disease, and 1 with "pure HpScl." Conclusions: HpScl is common in an elderly cohort with dementia, occurring in 14% of the cases in this series, and 89% have TDP-43 pathology, often associated with a risk variant in GRN. Patients with HpScl who present after the age of 75 years often have presentations consistent with AD, but at autopsy have non-Alzheimer pathologies. Elderly patients with HpScl may be mistaken for AD.
AB - Background: Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration. Methods: We studied the clinical and pathologic features of HpScl in 205 consecutive patients with dementia who came to autopsy from 1997 to 2008, focusing on associations with TAR DNA-binding protein 43 (TDP-43) pathology and allelic variants in the progranulin (GRN) and apolipoprotein E (APOE). RESULTS: Of the 205 dementia patients, 28 had HpScl (14%). TDP-43 pathology was more frequent in cases with HpScl compared with those without HpScl (89% vs. 24%). GRN rs5848 T-allele but not APOE ε4 was associated with HpScl. In cases of HpScl with TDP-43 pathology and age of onset after 75 years (n=11), 8 had Alzheimer disease (AD)-like amnestic syndrome, but most (6 of 8) had pathology not consistent with AD (Braak stage III or less), including 4 with frontotemporal lobar degeneration with TDP, 1 with diffuse Lewy body disease, and 1 with "pure HpScl." Conclusions: HpScl is common in an elderly cohort with dementia, occurring in 14% of the cases in this series, and 89% have TDP-43 pathology, often associated with a risk variant in GRN. Patients with HpScl who present after the age of 75 years often have presentations consistent with AD, but at autopsy have non-Alzheimer pathologies. Elderly patients with HpScl may be mistaken for AD.
KW - Alzheimer disease
KW - amnestic syndrome
KW - hippocampal sclerosis
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U2 - 10.1097/WAD.0b013e31820f8f50
DO - 10.1097/WAD.0b013e31820f8f50
M3 - Article
C2 - 21346515
AN - SCOPUS:81855175349
SN - 0893-0341
VL - 25
SP - 364
EP - 368
JO - Alzheimer disease and associated disorders
JF - Alzheimer disease and associated disorders
IS - 4
ER -