Advertisement

Acta Neuropathologica

, Volume 88, Issue 3, pp 212–221 | Cite as

Hippocampal sclerosis: a common pathological feature of dementia in very old (≥80 years of age) humans

  • D. W. Dickson
  • P. Davies
  • C. Bevona
  • K. H. Van Hoeven
  • S. M. Factor
  • E. Grober
  • M. K. Aronson
  • H. A. Crystal
Regular Paper

Abstract

In a neuropathological study of 81 brains of prospectively studied subjects of 80 years of age or older at the time of death, 13 cases (16%), including 4 men and 9 women, had hippocampal sclerosis (HpScl) affecting the vulnerable region of the hippocampus. In demented subjects of 80 years of age or older, the frequency of HpScl was even higher, 26%. Cases with HpScl had significantly fewer hippocampal senile plaques (SP) and neurofibrillary tangles (NFT) and parahippocampal NFT than cases without HpScl, but did not differ significantly in any of the other measured pathological parameters. Enzyme-linked analysis of synaptic protein immunoreactivity in a subset of 33 cases demonstrated significant decreases in the hippocampus, but not in frontal, temporal, parietal or parahippocampal cortices. All but 1 of the cases with HpScl had Blessed information, memory and concentration scores (BIMC) of 8 or more, and all were considered to be demented. In some patients memory disturbance was disproportionate to deficits in other cognitive areas. All but 4 of the cases with HpScl had many nonneuritic, amyloid plaques in the neocortex meeting NIA criteria for Alzheimer's disease (AD); however, given the advanced age of the subjects, amyloid plaques were considered to represent age-related cerebral amyloid deposition (“pathological aging”) in most cases. Only 3 cases had both many SP and NFT in multiple cortical regions consistent with AD. Another case had brain stem and cortical Lewy bodies consistent with diffuse Lewy body disease (DLBD). A few ballooned neurons were present in the limbic cortices in 3 cases, including one case of dementia with argyrophilic grains (DAG) in limbic and orbital frontal and temporal cortices. The 8 cases without AD, DLBD or DAG included 4 cases in which no other obvious cause of dementia was detected and 4 cases in which HpScl was accompanied by either multiple cerebral infarcts or leukoencephalopathy, or both, that could have contributed to dementia. Patients with HpScl had risk factors, clinical signs and post-mortem pathological findings of cardiovascular disease, but due to the high prevalence of these conditions in very old humans, no significant correlation with HpScl was detected. This study demonstrates that HpScl is a common post-mortem finding in demented, but not normal, elderly subjects. It may contribute to, or be a marker for, the increased risk of dementia in subjects with documented cardiovascular disease or a history of myocardial infarction.

Key words

Dementia Hippocampus Ischemia Synaptic proteins Vascular disease 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Aronson MK, Ooi WL, Morgenstern H, Hafner A, Masur D, Crystal H, Frishman WH, Fisher D, Katzman R (1990) Women, myocardial infarction, and dementia in the very old. Neurology 40: 1102–1106Google Scholar
  2. 2.
    Bell MA, Ball MJ (1986) The correlation of vascular capacity with the parenchymal lesions of Alzheimer's disease. Can J Neurol Sci 13: 456–461Google Scholar
  3. 3.
    Blessed G, Tomlinson GE, Roth M (1968) The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 114: 797–811Google Scholar
  4. 4.
    Braak H, Braak E (1989) Cortical and subcortical argyrophilic grains characterize a disease associated with adult onset dementia. Neuropathol Appl Neurobiol 15: 13–26Google Scholar
  5. 5.
    Buchan AM, Pusinelli WA (1990) Septo-hippocampal deafferentation protects CA1 neurons against ischemic injury. Brain Res 512: 7–14Google Scholar
  6. 6.
    Butler RN (1991) The challenge of geriatric medicine. In: Wilson JD, Braunwald E, Isselbacher KJ, Petersdorf RG, Martin JB, Fauci AS, Root RK (eds) Harrison's principles of internal medicine, 12th edn. McGraw-Hill, New York, pp 16–19Google Scholar
  7. 7.
    Clark AW, White CL III, Manz HJ, Parhad IM, Curry B, Whitehouse PJ, Lehmann J, Coyle JT (1986) Primary degenerative dementia without Alzheimer pathology. Can J Neurol Sci 13: 462–470Google Scholar
  8. 8.
    Crystal H, Dickson D (1992) Ischemic dementia and not Alzheimer's disease is the most frequent cause of dementia in autopsy studies of very old subjects (abstract). Neurobiol Aging 13: S34Google Scholar
  9. 9.
    Crystal H, Dickson D, Fuld P, Masur D, Scott R, Mehler M, Masdeu J, Kawas C, Aronson M, Wolfson L (1988) Clinicopathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 38: 1682–1687Google Scholar
  10. 10.
    Crystal HA, Dickson DW, Sliwinski M, Lipton R, Grober E, Marks-Nelson H, Antis P (1993) Pathological markers associated with normal aging and dementia in the elderly. Ann Neurol 34: 566–573Google Scholar
  11. 11.
    DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 27: 457–464Google Scholar
  12. 12.
    del Ser T, Bermejo F, Portera A, Arredondo JM, Bouras C, Constantinidis J (1990) Vascular dementia. A clinicopathological study. J Neurol Sci 96: 1–17Google Scholar
  13. 13.
    Delaere P, Duyckaerts C, Masters C, Beyreuther K, Piette F, Hauw JJ (1990) Large amounts of neocortical beta/A4 deposits without neuritic plaques nor tangles in a psychometrically assessed, non-demented person. Neurosci Lett 116: 87–93Google Scholar
  14. 14.
    Dickson DW, Yen S-H, Suzuki KI, Davies P, Garcia JH, Hirano A (1986) Ballooned neurons in select neurodegenerative diseases contain phosphorylated neurofilament epitopes. Acta Neuropathol (Berl) 71: 216–223Google Scholar
  15. 15.
    Dickson DW, Farlo J, Davies P, Crystal H, Fuld P, Yen S-H (1988) Alzheimer's disease: a double-labeling immunohistochemical study of senile plaques. Am J Pathol 132: 86–101Google Scholar
  16. 16.
    Dickson DW, Crystal H, Mattiace LA, Kress Y, Schwagerl A, Ksiezak-Reding H, Davies P, Yen S-H (1989) Diffuse Lewy body disease: light and electron microscopic immunocytochemistry of senile plaques. Acta Neuropathol 78: 572–584Google Scholar
  17. 17.
    Dickson DW, Crystal HA, Mattiace LA, Masur DM, Blau AD, Davies P, Yen S-H, Aronoson MK (1991) Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol Aging 13: 179–189Google Scholar
  18. 18.
    Erkinjuntti T, Haltia M, Palo J, Sulkava R, Paetau A (1988) Accuracy of the clinical diagnosis of vascular dementia: a prospective clinical and post-mortem neuropathological study. J Neurol Neurosurg Psychiatry 51: 1037–1044Google Scholar
  19. 19.
    Fuld PA (1981) The Fuld Object Memory Test. Stoelting Instrument Co. ChicagoGoogle Scholar
  20. 20.
    Garcia JH, Brown GG (1992) Vascular dementia: neuropathologic alterations and metabolic brain changes. J Neurol Sci 109: 121–131Google Scholar
  21. 21.
    Globu MY, Busto R, Martinez E, Valdes I, Dietrich WD, Ginsberg MD (1991) Comparative effect of transient global ischemia on extracellular levels of glutamate, glycine, and gamma-aminobutyric acid in vulnerable and nonvulnerable brain regions in the rat. J Neurochem 57: 470–478Google Scholar
  22. 22.
    Gustafson L, Brun A, Hagberg B, Johanson A, Minthon L, Passant U, Risberg J, Rosen IA (1992) Long-term dementia study. A 25-year perspective on differential diagnostic criteria (abstract). Neurobiol Aging 13: S6Google Scholar
  23. 23.
    Hachinski VC, Lassen NA, Marshall J (1974) Multi-infarct dementia: a cause of mental deterioration in the elderly. Lancet II: 207–210Google Scholar
  24. 24.
    Honer WG, Dickson DW, Gleeson J, Davies P (1992) Regional synaptic pathology in Alzheimer's disease. Neurobiol Aging 13: 375–382Google Scholar
  25. 25.
    Inzitari D, Diaz F, Fox A, Hachinski VC, Steingart A, Lau C, Donald A, Wade J, Mulic H, Merskey H (1987) Vascular risk factors and leuko-araiosis. Arch Neurol 4: 42–47Google Scholar
  26. 26.
    Jellinger K, Danielczyk W, Fischer W, Gabriel E (1990) Clinicopathological analysis of dementia disorders in the elderly. J Neurol Sci 95: 239–258Google Scholar
  27. 27.
    Katzman R, Terry RD, DeTeresa R, Brown T, Davies P, Fuld P, Renbing X, Peck A (1988) Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques. Ann Neurol 23: 138–144Google Scholar
  28. 28.
    Katzman R, Aronson M, Fuld P, Kawas C, Brown T, Morgenstern H, Frishman W, Gidez L, Eder H, Ooi WL (1989) Development of dementing illnesses in an 80-year-old volunteer cohort. Ann Neurol 25: 317–324Google Scholar
  29. 29.
    Kemper TL (1978) Senile dementia: a focal disease in the temporal lobe. In: Nandy K (ed) Senile dementia: a biomedical approach. Elsevier North-Holland, Amsterdam, pp 105–113Google Scholar
  30. 30.
    Khachaturian ZS (1985) Diagnosis of Alzheimer's disease. Arch Neurol 42: 1097–1105Google Scholar
  31. 31.
    Knopman DS, Mastri AR, Fery WH II, Sung JH, Rustan T (1990) Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 40: 251–256Google Scholar
  32. 32.
    Lee KS, Frank S, Vanderklish P, Arai A, Lynch G (1991) Inhibition of proteolysis protects hippocampal neurons from ischemia. Proc Natl Acad Sci USA 88: 7233–7237Google Scholar
  33. 33.
    Loeb C (1990) Vascular dementia. Dementia 1: 175–184Google Scholar
  34. 34.
    Mann DMA, Eaves NR, Marcyniuk B, Yates PO (1986) Quantitative changes in cerebral cortical microvasculature in ageing and dementia. Neurobiol Aging 7: 321–330Google Scholar
  35. 35.
    Markowitsch HJ, Pritzel M (1985) The neuropathology of amnesia. Prog Neurobiol 25: 190–264Google Scholar
  36. 36.
    McKee AC, Kosik KS, Kowall NW (1991) Neuritic pathology and dementia in Alzheimer's disease. Ann Neurol 30: 156–165Google Scholar
  37. 37.
    Munoz DG (1991) The pathological basis of multi-infarct dementia. Alzheimer Dis Assoc Disord 5: 77–90Google Scholar
  38. 38.
    Nowicki JP, Duval D, Poignet H, Scatton B (1991) Nitric oxide mediates neuronal death after focal ischemia in the mouse. Eur J Pharmacol 204: 125–128Google Scholar
  39. 39.
    Roman GC (1987) Senile dementia of the Binswanger type: a vascular form of dementia in the elderly. JAMA 258: 1782–1788Google Scholar
  40. 40.
    Skoog I, Nilsson L, Palmertz B, Andreasson L-A, Svanborg A (1993) A population-based study of dementia in 85-year-olds. N Engl J Med 328: 153–158Google Scholar
  41. 41.
    Sparks DL, Hunsaker JC, Scheff SW, Kryscio RJ, Henson JL, Markesbery WR (1990) Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease. Neurobiol Aging 11: 601–607Google Scholar
  42. 42.
    Terry RD, Masliah E, Salmon D, Butters N, DeTeresa R, Hill R, Hansen L, Katzman R (1991) Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30: 572–580Google Scholar
  43. 43.
    Tomlinson BE, Blessed G, Roth M (1968) Observations on the brains of nondemented old people. J Neurol Sci 7: 331–356Google Scholar
  44. 44.
    Volpe BT, Petito CK (1985) Dementia with bilateral medial temporal lobe ischemia. Neurology 35: 1793–1797Google Scholar
  45. 45.
    Wilcock GK, Esiri MM (1982) Plaques, tangles and dementia: a quantitative study. J Neurol Sci 56: 407–417Google Scholar
  46. 46.
    Wu E, Lipton RB, Dickson DW (1992) Amyloid angiopathy in diffuse Lewy body disease. Neurology 42: 2131–2135Google Scholar
  47. 47.
    Zweig R, Schegg KM, Peacock JH, Melarkey D (1989) A case of Alzheimer's disease and hippocampal sclerosis with normal cholinergic activity in basal forebrain, neocortex, and hippocampus. Neurology 39: 288–290Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • D. W. Dickson
    • 1
    • 2
  • P. Davies
    • 1
    • 3
  • C. Bevona
    • 1
  • K. H. Van Hoeven
    • 1
  • S. M. Factor
    • 1
    • 4
  • E. Grober
    • 2
  • M. K. Aronson
    • 2
  • H. A. Crystal
    • 2
  1. 1.Department of PathologyAlbert Einstein College of MedicineBronxUSA
  2. 2.Department of NeurologyAlbert Einstein College of MedicineBronxUSA
  3. 3.Department of NeuroscienceAlbert Einstein College of MedicineBronxUSA
  4. 4.Department of MedicineAlbert Einstein College of MedicineBronxUSA

Personalised recommendations