Hippocampal sclerosis in the elderly: Genetic and pathologic findings, some mimicking Alzheimer disease clinically

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalAlzheimer Disease and Associated Disorders
Volume25
Issue number4
DOIs
StatePublished - Oct 2011

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Sclerosis
Alzheimer Disease
DNA-Binding Proteins
Pathology
Dementia
Autopsy
Frontotemporal Lobar Degeneration
Apolipoprotein E4
Lewy Body Disease
Apolipoproteins E
Age of Onset
Alleles

Keywords

  • Alzheimer disease
  • amnestic syndrome
  • hippocampal sclerosis

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Gerontology
  • Clinical Psychology

Cite this

@article{03a4250c8ddf4336b6924ba17c0aac49,
title = "Hippocampal sclerosis in the elderly: Genetic and pathologic findings, some mimicking Alzheimer disease clinically",
abstract = "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.",
keywords = "Alzheimer disease, amnestic syndrome, hippocampal sclerosis",
author = "Pao, {Winnie C.} and Dickson, {Dennis W} and Juliana Crook and Finch, {Nicole A.} and Rademakers, {Rosa V} and {Graff Radford}, {Neill R}",
year = "2011",
month = "10",
doi = "10.1097/WAD.0b013e31820f8f50",
language = "English (US)",
volume = "25",
pages = "364--368",
journal = "Alzheimer Disease and Associated Disorders",
issn = "0893-0341",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

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, Juliana

AU - Finch, Nicole A.

AU - Rademakers, Rosa V

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

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AN - SCOPUS:81855175349

VL - 25

SP - 364

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JO - Alzheimer Disease and Associated Disorders

JF - Alzheimer Disease and Associated Disorders

SN - 0893-0341

IS - 4

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