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Understanding hippocampal sclerosis in the elderly: Epidemiology, characterization, and diagnostic issues

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Abstract

Hippocampal sclerosis (HS) is a pathologic term used to describe severe loss of neurons and reactive gliosis without cystic cavitation in the CA1 sector of the hippocampus. In late life, HS is associated with hippocampal atrophy, severe amnesia, and slowly progressive dementia without clinical seizure activity. HS is difficult to distinguish clinically from Alzheimer’s disease and is often diagnosed postmortem. In autopsy series, HS may be found without significant other pathology (2%–4% of cases), but it occurs frequently in combination with other vascular and neurodegenerative disorders (12%–20% of cases). HS is found bilaterally in 50% of cases and unilaterally in 50% of cases, with similar predilection for the right versus left hemisphere. The pathogenesis of HS is unknown and may be multifactorial in origin, possibly due to anoxic/ischemic injury or TDP-43-related neurodegeneration. Little is known about the prevention and treatment of late-life HS, although circumstantial evidence suggests the importance of identifying and treating vascular risk factors.

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References and Recommended Reading

  1. Blass DM, Hatanpaa KJ, Brandt J, et al.: Dementia in hippocampal sclerosis resembles frontotemporal dementia more than Alzheimer disease. Neurology 2004, 63:492–497.

    PubMed  CAS  Google Scholar 

  2. Silver MH, Newell K, Brady C, et al.: Distinguishing between neurodegenerative disease and disease-free aging: correlating neuropsychological evaluations and neuropathological studies in centenarians. Psychosom Med 2002, 64:493–501.

    PubMed  Google Scholar 

  3. Gearing M, Mirra SS, Hedreen JC, et al.: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer’s disease. Neurology 1995, 45:461–466.

    PubMed  CAS  Google Scholar 

  4. Jack CR Jr, Dickson DW, Parisi JE, et al.: Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia. Neurology 2002, 58:750–757.

    PubMed  Google Scholar 

  5. Jellinger KA: Hippocampal sclerosis: a common pathological feature of dementia in very old humans. Acta Neuropathol (Berl) 1994, 88:599.

    Article  CAS  Google Scholar 

  6. Jellinger K: Pure hippocampal sclerosis: a rare cause of dementia mimicking Alzheimer’s disease. Neurology 2000, 55:739–740.

    PubMed  CAS  Google Scholar 

  7. Rasmusson DX, Brandt J, Steele C, et al.: Accuracy of clinical diagnosis of Alzheimer disease and clinical features of patients with non-Alzheimer disease neuropathology. Alzheimer Dis Assoc Disord 1996, 10:180–188.

    Article  PubMed  CAS  Google Scholar 

  8. Beach TG, Sue L, Scott S, et al.: Hippocampal sclerosis dementia with tauopathy. Brain Pathol 2003, 13:263–278.

    Article  PubMed  Google Scholar 

  9. Dickson DW, Davies P, Bevona C, et al.: Hippocampal sclerosis: a common pathological feature of dementia in very old (> or = 80 years of age) humans. Acta Neuropathol (Berl) 1994, 88:212–221.

    Article  CAS  Google Scholar 

  10. Ishizawa T, Ko LW, Cookson N, et al.: Selective neurofibrillary degeneration of the hippocampal CA2 sector is associated with four-repeat tauopathies. J Neuropathol Exp Neurol 2002, 61:1040–1047.

    PubMed  CAS  Google Scholar 

  11. Barker WW, Luis CA, Kashuba A, et al.: Relative frequencies of Alzheimer disease, Lewy body, vascular and frontotemporal dementia, and hippocampal sclerosis in the State of Florida Brain Bank. Alzheimer Dis Assoc Disord 2002, 16:203–212.

    Article  PubMed  Google Scholar 

  12. Zarow C, Vinters HV, Ellis WG, et al.: Correlates of hippocampal neuron number in Alzheimer’s disease and ischemic vascular dementia. Ann Neurol 2005, 57:896–903.

    Article  PubMed  Google Scholar 

  13. Marshall GA, Mendez MF, Fairbanks L, et al.: Presence of hippocampal sclerosis in the elderly and co-occurrence with different dementias. Ann Neurol 2005, 58(Suppl 9):S16.

    Google Scholar 

  14. Amador-Ortiz C, Ahmed Z, Zehr C, et al.: Hippocampal sclerosis dementia differs from hippocampal sclerosis in frontal lobe degeneration. Acta Neuropathol (Berl) 2007, 113:245–252.

    Article  Google Scholar 

  15. Attems J, Jellinger KA: Hippocampal sclerosis in Alzheimer disease and other dementias. Neurology 2006, 66:775.

    Article  PubMed  Google Scholar 

  16. Jellinger KA: Pathology and pathophysiology of vascular cognitive impairment. a critical update. Panminerva Medica 2004, 46:217–226.

    PubMed  CAS  Google Scholar 

  17. del Ser T, Hachinski V, Merskey H, et al.: Alzheimer’s disease with and without cerebral infarcts. J Neurol Sci 2005, 231:3–11.

    Article  PubMed  Google Scholar 

  18. Barkhof F, Polvikoski TM, van Straaten EC, et al.: The significance of medial temporal lobe atrophy: a postmortem MRI study in the very old. Neurology 2007, 69:1521–1527.

    Article  PubMed  CAS  Google Scholar 

  19. Nakano I: Frontotemporal dementia with motor neuron disease (amyotrophic lateral sclerosis with dementia). Neuropathology 2000, 20:68–75.

    Article  PubMed  CAS  Google Scholar 

  20. Josephs KA, Dickson DW, Josephs KA, et al.: Hippocampal sclerosis in tau-negative frontotemporal lobar degeneration. Neurobiol Aging 2007, 28:1718–1722.

    Article  PubMed  CAS  Google Scholar 

  21. Josephs KA, Whitwell JL, Jack CR, et al.: Frontotemporal lobar degeneration without lobar atrophy. Arch Neurol 2006, 63:1632–1638.

    Article  PubMed  Google Scholar 

  22. Josephs KA, Ahmed Z, Katsuse O, et al.: Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions with progranulin gene (PGRN) mutations. J Neuropathol Exp Neurol 2007, 66:142–151.

    Article  PubMed  CAS  Google Scholar 

  23. Leverenz JB, Agustin CM, Tsuang D, et al.: Clinical and neuropathological characteristics of hippocampal sclerosis: a community-based study. Arch Neurol 2002, 59:1099–1106.

    Article  PubMed  Google Scholar 

  24. Vinters HV, Ellis WG, Zarow C, et al.: Neuropathologic substrates of ischemic vascular dementia. J Neuropathol Exper Neurol 2000, 59:931–945.

    CAS  Google Scholar 

  25. Chui HC, Zarow C, Mack WJ, et al.: Cognitive impact of subcortical vascular and Alzheimer’s disease pathology. Ann Neurol 2006, 60:677–687.

    Article  PubMed  Google Scholar 

  26. Dickson DW, Ruan D, Crystal H, et al.: Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer’s disease: light and electron microscopic immunocytochemistry of CA2-3 neurites specific to DLBD. Neurology 1991, 41:1402–1409.

    PubMed  CAS  Google Scholar 

  27. Hatanpaa KJ, Blass DM, Pletnikova O, et al.: Most cases of dementia with hippocampal sclerosis may represent frontotemporal dementia. Neurology 2004, 63:538–542.

    PubMed  CAS  Google Scholar 

  28. Crystal HA, Dickson D, Davies P, et al.: The relative frequency of “dementia of unknown etiology” increases with age and is nearly 50% in nonagenarians. Arch Neurol 2000, 57:713–719.

    Article  PubMed  CAS  Google Scholar 

  29. Josephs KA, Jones AG, Dickson DW: Hippocampal sclerosis and ubiquitin-positive inclusions in dementia lacking distinctive histopathology. Dementia Geriatr Cogn Disord 2004, 17:342–345.

    Article  Google Scholar 

  30. Knopman DS, Mastri AR, Frey WH, et al.: Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 1990, 40:251–256.

    PubMed  CAS  Google Scholar 

  31. Amador-Ortiz C, Lin WL, Ahmed Z, et al.: TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 2007, 61:435–445.

    Article  PubMed  CAS  Google Scholar 

  32. Schneider JA, Watts RL, Gearing M, et al.: Corticobasal degeneration: neuropathologic and clinical heterogeneity. Neurology 1997, 48:959–969.

    PubMed  CAS  Google Scholar 

  33. Schneider JA, Arvanitakis Z, Bang W, et al.: Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 2007, 69:2197–2204.

    Article  PubMed  Google Scholar 

  34. Corey-Bloom J, Sabbagh MN, Bondi MW, et al.: Hippocampal sclerosis contributes to dementia in the elderly. Neurology 1997, 48:154–160.

    PubMed  CAS  Google Scholar 

  35. Ala TA, Beh GO, Frey WH: Pure hippocampal sclerosis: a rare cause of dementia mimicking Alzheimer’s disease. Neurology 2000, 54:843–848.

    PubMed  CAS  Google Scholar 

  36. White L, Petrovitch H, Hardman J, et al.: Cerebrovascular pathology and dementia in autopsied Honolulu-Asia Aging Study participants. Ann NY Acad Sci 2002, 977:9–23.

    Article  PubMed  Google Scholar 

  37. Petersen RC, Parisi JE, Dickson DW, et al.: Neuropathologic features of amnestic mild cognitive impairment. Arch Neurol 2006, 63:665–672.

    Article  PubMed  Google Scholar 

  38. Ikemoto A, Hirano A, Akiguchi I, et al.: Comparative study of ubiquitin immunoreactivity of hippocampal granular cells in amyotrophic lateral sclerosis with dementia, Guamanian amyotrophic lateral sclerosis and Guamanian parkinsonism-dementia complex. Acta Neuropathol (Berl) 1997, 93:265–270.

    Article  CAS  Google Scholar 

  39. Josephs KA, Jones AG, Dickson DW: Hippocampal sclerosis and ubiquitin-positive inclusions in dementia lacking distinctive histopathology. Dementia Geriatr Cogn Disord 2004, 17:342–345.

    Article  Google Scholar 

  40. Probst A, Taylor KI, Tolnay M, et al.: Hippocampal sclerosis dementia: a reappraisal. Acta Neuropathol (Berl) 2007, 114:335–345.

    Article  Google Scholar 

  41. Zabar Y: Dementia due to hippocampal sclerosis: clinical features and comparison to Alzheimer’s disease. Neurology 1998, 50(Suppl):A60.

    Google Scholar 

  42. Jagust WJ, Zheng L, Harvey DJ, et al.: Neuropathological basis of magnetic resonance images in aging and dementia. Ann Neurol 2008, 63:72–80.

    Article  PubMed  Google Scholar 

  43. Mendez MF, Chow T, Ringman J, et al.: Pedophilia and temporal lobe disturbances. J Neuropsychiatry Clin Neurosci 2000, 12:71–76.

    PubMed  CAS  Google Scholar 

  44. Jackson GD, Kuzniecky RI, Cascino GD, et al.: Hippocampal sclerosis without detectable hippocampal atrophy. Neurology 1994, 44:42–46.

    PubMed  CAS  Google Scholar 

  45. Duvernoy HM: The Human Hippocampus. New York: Springer-Verlag; 1998.

    Google Scholar 

  46. Volpe BT, Petito CK, Volpe BT, et al.: Dementia with bilateral medial temporal lobe ischemia. Neurology 1985, 35:1793–1797.

    PubMed  CAS  Google Scholar 

  47. Josephs KA, Whitwell JL, Knopman DS, et al.: Abnormal TDP-43 immunoreactivity in AD modifies clinicopathologic and radiologic phenotype. Neurology 2008, 70:1850–1857.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Rancho Los Amigos National Rehabilitation Center, University of Southern California, 7601 E. Imperial Highway, Medical Science Building, Room 26, Downey, CA, 90242, USA

    Chris Zarow

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  1. Chris Zarow
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  2. Traci E. Sitzer
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  3. Helena C. Chui
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Correspondence to Chris Zarow.

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Zarow, C., Sitzer, T.E. & Chui, H.C. Understanding hippocampal sclerosis in the elderly: Epidemiology, characterization, and diagnostic issues. Curr Neurol Neurosci Rep 8, 363–370 (2008). https://doi.org/10.1007/s11910-008-0057-3

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