CoChat
Sign Up
Cited by 108Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Hippocampal sclerosis of aging is a key Alzheimer’s disease mimic: Clinical-pathologic correlations and comparisons with both Alzheimer’s disease and non-tauopathic frontotemporal lobar degeneration

Open access
Brenowitz, Willa D., Monsell, Sarah E., Schmitt, Frederick A., Kukull, Walter A., Nelson, Peter T.·2014·Journal of Alzheimer's Disease
DOI 10.3233/jad-131880PMC PMC3946156
Open this paper in CoChat — free account

Abstract

Hippocampal sclerosis of aging (HS-Aging) neuropathology was observed in more than 15% of aged individuals in prior studies. However, much remains unknown about the clinical correlates of HS-Aging pathology or the association(s) between HS-Aging, Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) pathology. Clinical and comorbid pathological features linked to HS-Aging pathology were analyzed using National Alzheimer's Coordinating Center (NACC) data. From autopsy data extending back to 1990 (n = 9,817 participants), the neuropathological diagnoses were evaluated from American AD Centers (ADCs). Among participants who died between 2005-2012 (n = 1,422), additional analyses identified clinical and pathological features associated with HS-Aging pathology. We also compared cognitive testing and longevity outcomes between HS-Aging cases and a subsample with non-tauopathy FTLD (n = 210). Reporting of HS-Aging pathology increased dramatically among ADCs in recent years, to nearly 20% of autopsies in 2012. Participants with relatively "pure" HS-Aging pathology were often diagnosed clinically as having probable (68%) or possible (15%) AD. However, the co-occurrence of HS-Aging pathology and AD neuropathology (AD-NP) did not indicate any pattern of correlation between the two pathologies. Compared with other pathologies, participants with HS-Aging pathology had higher overall cognitive/functional ability (versus AD-NP) and verbal fluency (versus both AD-NP and FTLD) but similar episodic memory impairment at one clinic visit 2-5 years prior to death. Patients with HS-Aging live considerably longer than patients with non-tauopathy FTLD. We conclude that the manifestations of HS-Aging, increasingly recognized in recent years, probably indicate a separate disease process of direct relevance to patient care, dementia research, and clinical trials.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3233/jad-131880

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Over 80% of participants with pure HS pathology were diagnosed with possible or probable AD prior to death, indicating that HS pathology strongly mimics AD pathology clinically.

    “Despite this, over 80% of participants with”

    From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [9]

  • Another study using NACC data compared hippocampal sclerosis (HS) pathology with AD pathology, finding less cognitive impairment in persons with HS versus AD pathology.

    “Another study data aimed to address this, using NACC data to compare hippocampal sclerosis (HS) pathology with AD pathology, finding less cognitive impairment in persons with HS versus AD pathology.”

    From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [9]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 26

  1. [1]Amador-Ortiz C Ahmed Z Zehr C Dickson DW 2007 Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe degeneration Acta Neuropathol 113 245 252 17195931 PMC1794627
  2. [2]Nelson PT Schmitt FA Lin Y Abner EL Jicha GA Patel E Thomason PC Neltner JH Smith CD Santacruz KS Sonnen JA Poon LW Gearing M Green RC Woodard JL Van Eldik LJ Kryscio RJ 2011 Hippocampal sclerosis in advanced age: clinical and pathological features Brain 134 1506 1518 21596774 PMC3097889
  3. [3]Zarow C Weiner MW Ellis WG Chui HC 2012 Prevalence, laterality, and comorbidity of hippocampal sclerosis in an autopsy sample Brain Behav 2 435 442 22950047 PMC3432966
  4. [4]Nelson PT Smith CD Abner EL Wilfred BJ Wang W-X Neltner JH Baker M Fardo DW Kryscio RJ Scheff SW Jicha GA Jellinger KA Van Eldik LJ Schmitt FA 2013 Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease Acta Neuropathol 126 161 177 23864344 PMC3889169
  5. [5]Pao WC Dickson DW Crook JE Finch NA Rademakers R Graff-Radford NR 2011 Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically Alzheimer Dis Assoc Disord 25 364 368 21346515 PMC3107353
  6. [6]Nelson PT Abner EL Schmitt FA Kryscio RJ Jicha GA Smith CD Davis DG Poduska JW Patel E Mendiondo MS Markesbery WR 2010 Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons Brain Pathol 20 66 79 19021630 PMC2864342
  7. [8]Amador-Ortiz C Lin WL Ahmed Z Personett D Davies P Duara R Graff-Radford NR Hutton ML Dickson DW 2007 TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease Ann Neurol 61 435 445 17469117 PMC2677204
  8. [9]Dickson DW Baker M Rademakers R 2010 Common variant in GRN is a genetic risk factor for hippocampal sclerosis in the elderly Neurodegener Dis 7 170 174 20197700 PMC2859236
  9. [10]Rutherford NJ Carrasquillo MM Li M Bisceglio G Menke J Josephs KA Parisi JE Petersen RC Graff-Radford NR Younkin SG Dickson DW Rademakers R 2012 TMEM106B risk variant is implicated in the pathologic presentation of Alzheimer disease Neurology 79 717 718 22855871 PMC3467659
  10. [11]Mirra SS Heyman A McKeel D Sumi SM Crain BJ Brownlee LM Vogel FS Hughes JP van Belle G Berg L 1991 The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease Neurology 41 479 486 2011243
  11. [13]Beekly DL Ramos EM van Belle G Deitrich W Clark AD Jacka ME Kukull WA 2004 The National Alzheimer's Coordinating Center (NACC) Database: an Alzheimer disease database Alzheimer Dis Assoc Disord 18 270 277 15592144
  12. [14]Morris JC Weintraub S Chui HC Cummings J DeCarli C Ferris S Foster NL Galasko D Graff-Radford N Peskind ER Beekly D Ramos EM Kukull WA 2006 The Uniform Data Set (UDS): Clinical and Cognitive Variables and Descriptive Data From Alzheimer Disease Centers Alzheimer Disease & Associated Disorders 20 210 216 17132964
  13. [15]Beekly DL Ramos EM Lee WW Deitrich WD Jacka ME Wu J Hubbard JL Koepsell TD Morris JC Kukull WA 2007 The National Alzheimer's Coordinating Center (NACC) database: the Uniform Data Set Alzheimer Dis Assoc Disord 21 249 258 17804958
  14. [17]McKeith IG Dickson DW Lowe J Emre M O'Brien JT Feldman H Cummings J Duda JE Lippa C Perry EK Aarsland D Arai H Ballard CG Boeve B Burn DJ Costa D Del Ser T Dubois B Galasko D Gauthier S Goetz CG Gomez-Tortosa E Halliday G Hansen LA Hardy J Iwatsubo T Kalaria RN Kaufer D Kenny RA Korczyn A Kosaka K Lee VMY Lees A Litvan I Londos E Lopez OL Minoshima S Mizuno Y Molina JA Mukaetova-Ladinska EB Pasquier F Perry RH Schulz JB Trojanowski JQ Yamada M 2005 Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium Neurology 65 1863 1872 16237129
  15. [18]Morris JC 1993 The Clinical Dementia Rating (CDR): current version and scoring rules Neurology 43 2412 2414 8232972
  16. [21]McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM 1984 Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease Neurology 34 939 944 6610841
  17. [22]McKeith IG Galasko D Kosaka K Perry EK Dickson DW Hansen LA Salmon DP Lowe J Mirra SS Byrne EJ Lennox G Quinn NP Edwardson JA Ince PG Bergeron C Burns A Miller BL Lovestone S Collerton D Jansen EN Ballard C de Vos RA Wilcock GK Jellinger KA Perry RH 1996 Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop Neurology 47 1113 1124 8909416
  18. [23]Jellinger KA Attems J 2008 Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease Acta Neuropathol 115 427 436 18273624
  19. [24]Nelson PT Kryscio RJ Jicha GA Abner EL Schmitt FA Xu LO Cooper G Smith CD Markesbery WR 2009 Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies Neurology 73 1127 1133 19805729 PMC2764396
  20. [25]O'Bryant SE Waring SC Cullum CM Hall J Lacritz L Massman PJ Lupo PJ Reisch JS Doody R 2008 Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study Arch Neurol 65 1091 1095 18695059 PMC3409562
  21. [26]Sonnen JA Larson EB Crane PK Haneuse S Li G Schellenberg GD Craft S Leverenz JB Montine TJ 2007 Pathological correlates of dementia in a longitudinal, population-based sample of aging Ann Neurol 62 406 413 17879383
  22. [27]Leverenz JB Lipton AM 2008 Clinical aspects of hippocampal sclerosis Handb Clin Neurol 89 565 567 18631778
  23. [28]Troncoso JC Kawas CH Chang CK Folstein MF Hedreen JC 1996 Lack of association of the apoE4 allele with hippocampal sclerosis dementia Neurosci Lett 204 138 140 8929997
  24. [29]Nelson PT Alafuzoff I Bigio EH Bouras C Braak H Cairns NJ Castellani RJ Crain BJ Davies P Del Tredici K Duyckaerts C Frosch MP Haroutunian V Hof PR Hulette CM Hyman BT Iwatsubo T Jellinger KA Jicha GA Kövari E Kukull WA Leverenz JB Love S Mackenzie IR Mann DM Masliah E McKee AC Montine TJ Morris JC Schneider JA Sonnen JA Thal DR Trojanowski JQ Troncoso JC Wisniewski T Woltjer RL Beach TG 2012 Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature J Neuropathol Exp Neurol 71 362 381 22487856 PMC3560290
  25. [30]Giannakopoulos P Bouras C Hof PR 2008 Clinicopathologic correlates in the oldest-old: Commentary on “No disease in the brain of a 115-year-old woman.” Neurobiol Aging 29 1137 1139 18534719 PMC2911139
  26. [31]Nelson PT Head E Schmitt FA Davis PR Neltner JH Jicha GA Abner EL Smith CD Van Eldik LJ Kryscio RJ Scheff SW 2011 Alzheimer's disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies Acta Neuropathol 121 571 587 21516511 PMC3179861

Cited by

Sorted by citations

Authors
Brenowitz, W. D., Monsell, S. E., Schmitt, F. A., Kukull, W. A., & Nelson, P. T.
Affiliations
  • University of Washington (US)
  • University of Kentucky (US)
ORCID
Venue
Journal of Alzheimer's Disease
Publisher
SAGE Publications
Published
2014-02-07
Volume
39
Issue
3
Pages
691-702
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-131880
PMC
PMC3946156
OpenAlex
W1554748910
Cited by
108
References
4
Citations by year
2026: 2 · 2025: 8 · 2024: 7 · 2023: 12 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 10 · 2016: 10 · 2015: 8 · 2014: 5
FWCI
8.40
Type
journal article
Language
en
Open access
Locations
  • Journal of Alzheimer s Disease (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (P30AG028383, U01AG016976)
  • National Institute of Neurological Disorders and Stroke (R01NS061933)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
Alzheimer's disease
MeSH terms
Age Factors, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Autopsy, Female, Hippocampus, Humans, Male, Psychiatric Status Rating Scales, Sclerosis, Statistics as Topic, Neurofibrillary Tangles, tau Proteins, Frontotemporal Lobar Degeneration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review