Acta Neuropathologica

, Volume 89, Issue 4, pp 346–355 | Cite as

Dementia lacking distinctive histopathology: clinicopathological evaluation of 32 cases

  • P. Giannakopoulos
  • P. R. Hof
  • C. Bouras
Regular Paper


We report the neuropathological findings in 32 patients, aged 46–86 years, with demential lacking distinctive histopathology. All of the patients were classified clinically as having Pick's or atypical Pick's disease, but the routine neuropathological evaluation showed no specific histopathological changes such as Pick bodies, senile plaques, neurofibrillary tangles or Lewy bodies. In 50% of the cases the first symptoms appeared before 65 years of age. However, there were 9 patients with onset in the eighth decade. Positive family history was found only in 6 presenile cases. The retrospective evaluation of the clinical records revealed the consistent presence of “frontal” symptomatology, including loss of personal awareness, inappropriate euphoria and stereotyped behavior. Speech disorders were observed in 80% of the cases, whereas temporospatial disorientation and memory impairment were less frequent. Praxis and gnosis were strikingly preserved in most of the cases. The macroscopic neuropathological examination revealed frontal or temporopolar atrophy in 97% of the cases, while the hippocampus and subcortical structures were relatively spared in the majority of the cases. Histologically, four groups were recognized. Group A showed moderate to severe neuron loss and gliosis in the frontal and/or temporopolar cortex without subcortical involvement. In group B, the neocortical cell loss was widespread, and the striatum and substantia nigra displayed differential degrees of gliosis but no neuron loss. Group C patients showed a lesion distribution comparable to that observed in group B but with severe neuron loss in at least one subcortical region. Four cases formed group D, which was characterized by the preservation of the pyramidal neurons in the neocortex and variable subcortical changes. Despite these differences in the topography of pathological changes, all of the cases shared a similar clinical profile. These findings further demonstrate the epidemiological and neuropathological heterogeneity of dementia lacking distinctive histopathology. Furthermore, they suggest that the same clinical manifestations may correspond to several distinct pathological processes in this condition.

Key words

Frontal lobe Dementia Cerebral cortex Clinicopathological correlations 


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  1. 1.
    Brun A (1987) Frontal lobe degeneration of non-Alzheimer type. I. Neuropathology. Arch Gerontol Geriatr 6: 193–208Google Scholar
  2. 2.
    Brun A (1993) Frontal lobe degeneration of non-Alzheimer type revisited. Dementia 4: 126–131Google Scholar
  3. 3.
    Brun A, Englund B, Gustafson L, Passant U, Mann DMA, Neary D, Snowden JS (1994) Clinical and neuropathological criteria for frontotemporal dementia. J Neurol Neurosurg Psychiatry 57:416–418Google Scholar
  4. 4.
    Clark AW, White CL III, Manz HJ (1986) Primary degenerative dementia without Alzheimer pathology. Can J Neurol Sci 13:462–470Google Scholar
  5. 5.
    Collinge J, Palmer MS, Mahal SP, Campbell T, Brown J, Hardy J, Brun AE, Gustafson L, Bakker E, Roos R, Groen JJ (1994) Familial Pick's disease and dementia in frontal lobe degeneration of non-Alzheimer type are not variants of prion disease. J Neurol Neurosurg Psychiatry 57:762–768Google Scholar
  6. 6.
    Delacourte A, Flament S, Dibe EM, Hublau P, Sablonnière B, Hémon B, Scherrer V, Défossez A (1990) Pathological proteins Tau 64 and 69 are specifically expressed in the somatodendritic domain of the degenerating cortical neurons during Alzheimer's disease. Demonstration with a panel of antibodies against Tau proteins. Acta Neuropathol 80:111–117Google Scholar
  7. 7.
    Deymeer F, Smith TW, DeGirolami U, Drachman DA (1989) Thalamic dementia and motor neuron disease. Neurology 39: 58–61Google Scholar
  8. 8.
    Elfgren C, Passant U, Risberg J (1993) Neuropsychological findings in frontal lobe dementia. Dementia 4:214–219Google Scholar
  9. 9.
    Evans DA, Scherr PA, Cook NA, Albert MS, Funkenstein HH, Beckett LA, Hebert LE, Wetle FF, Branch LG, Chown MJ, Hennekens CH, Taylor JO (1992) The impact of Alzheimer's disease in the United States population. In: Suzman RM, Willis DP, Manton KG (eds) The oldest-old. Oxford University Press, New York, pp 283–299Google Scholar
  10. 10.
    Ferrer I, Roig C, Espino A, Peiró G, Matias Guiu X (1991) Dementia of frontal lobe type and motor neuron disease. A Golgi study of the frontal cortex. J Neurol Neurosurg Psychiatry 54: 932–934Google Scholar
  11. 11.
    Ferrer I, Tuñón T, Serrano MT, Casas R, Alcántara S, Zújar MJ, Rivera RM (1993) Calbindin D-28k and parvalbumin immunoreactivity in the frontal cortex in patients with frontal lobe dementia of non-Alzheimer type associated with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 56: 257–261Google Scholar
  12. 12.
    Flament S, Delacourte A, Delaère P, Duyckaerts C, Hauw JJ (1990) Correlations between microscopical changes and Tau 64 and 69 biochemical detection in senile dementia of the Alzheimer's type. Tau 64 and 69 are reliable markers of the neurofibrillary degeneration. Acta Neuropathol 80:212–215Google Scholar
  13. 13.
    Gustafson L (1987) Frontal lobe degeneration of non-Alzheimer type. II. Clinical picture and differential diagnosis. Arch Gerontol Geriatr 6:209–223Google Scholar
  14. 14.
    Gustafson L (1993) Clinical picture of frontal lobe degeneration of non-Alzheimer type. Dementia 4:143–148Google Scholar
  15. 15.
    Hof PR, Bouras C, Perl DP, Morrison JH (1994) Quantitative neuropathological analysis of Pick's disease cases: cortical distribution of Pick bodies and coexistence with Alzheimer's disease. Acta Neuropathol 87:115–124Google Scholar
  16. 16.
    Jellinger KA (1994) Quantitative neuropathologic analysis of Pick's disease cases. Acta Neuropathol 87:223–224Google Scholar
  17. 17.
    Kim KS, Miller DL, Sapienza VG, Chen CJ, Vai C, Grundke-Iqbal I, Curry JR, Wisniewski HM (1988) Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide. Neurosci Res Commun 2: 121–130Google Scholar
  18. 18.
    Knopman DS (1993) Overview of demential lacking distinctive histopathology: pathological designation of a progressive dementia. Dementia 4:132–136Google Scholar
  19. 19.
    Knopman DS, Mastri AR, Frey WH, Sung JH, Rustan T (1990) Dementia lacking distinctive histologic features: a common non-Alzheimer degenerative dementia. Neurology 40:251–266Google Scholar
  20. 20.
    Mann DMA, South PW (1993) The topographic distribution of brain atrophy in frontal lobe dementia. Acta Neuropathol 85: 334–340Google Scholar
  21. 21.
    Mann DMA, South PW, Snowden JS, Neary D (1993) Dementia of frontal lobe type: neuropathology and immunohistochemistry. J Neurol Neurosurg Psychiatry 56:605–614Google Scholar
  22. 22.
    Mendez MF, Selwood A, Mastri AR, Frey WH II (1993) Pick's disease versus Alzheimer's disease: a comparison of clinical characteristics. Neurology 43:289–292Google Scholar
  23. 23.
    Mesulam MM (1982) Slowly progressive aphasia without generalized aphasia. Ann Neurol 11:592–598Google Scholar
  24. 24.
    Moss M, Albert M (1988) Alzheimer's disease and other dementing disorders. In: Albert M, Moss M (eds) Geriatric neuropsychology. Guilford Press, New York, pp 145–177Google Scholar
  25. 25.
    Neary D (1990) Non-Alzheimer's disease forms of cerebral atrophy. J Neurol Neurosurg Psychiatry 53:929–931Google Scholar
  26. 26.
    Neary D, Snowden JS, Northen B, Goulding P (1988) Dementia of frontal lobe type. J Neurol Neurosurg Psychiatry 51: 353–361Google Scholar
  27. 27.
    Neary D, Snowden JS, Mann DMA, Northen B, Goulding PJ, McDermott N (1990) Frontal lobe dementia and motor neuron disease. J Neuron Neurosurg Psychiatry 53:23–32Google Scholar
  28. 28.
    Neary D, Snowden JS, Mann DMA (1993) The clinical pathological correlates of lobar atrophy. Dementia 4:154–159Google Scholar
  29. 29.
    Risberg J (1987) Frontal lobe degeneration of non-Alzheimer type. III. Regional cerebral blood flow. Arch Gerontol Geriatr 6:225–233Google Scholar
  30. 30.
    Risberg J, Passant U, Warkentin S, Gustafson L (1993) Regional cerebral blood flow in frontal lobe dementia of non-Alzheimer type. Dementia 4:186–187Google Scholar
  31. 31.
    Seitelberger F, Gross H, Pilz P (1983) Pick's disease: a neuropathological study. In: Hirano A, Miyoshi K (eds) Neuropsychiatric disorders in the elderly. Igaku-Shoin, Tokyo, pp 87–117Google Scholar
  32. 32.
    Snowden JS, Neary D, Mann MA, Goulding PJ, Testa HJ (1992) Progressive language disorder due to lobar atrophy. Ann Neurol 31:174–183Google Scholar
  33. 33.
    Starkstein SE, Migliorelli R, Tesón A, Sabe L, Vázquez S, Turjanski M, Robinson RG, Leiguarda R (1994) Specificity of changes in cerebral blood flow in patients with frontal lobe dementia. J Neurol Neurosurg Psychiatry 57:790–796Google Scholar
  34. 34.
    Torack RM, Morris JC (1986) Mesolimbocortical dementia. A clinicopathological case study of a putative disorder. Arch Neurol 43:1074–1078Google Scholar
  35. 35.
    Vallet PG, Guntern R, Hof PR, Golaz J, Delacourte A, Robakis NK, Bouras C (1992) A comparative study of histopathological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease. Acta Neuropathol 83:170–178Google Scholar
  36. 36.
    Verity MA, Roitberg B, Kepes JJ (1990) Mesolimbocortical dementia: clinicopathological studies on two cases. J Neurol Neurosurg Psychiatry 53:492–495Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • P. Giannakopoulos
    • 1
  • P. R. Hof
    • 2
    • 3
  • C. Bouras
    • 2
    • 4
  1. 1.Genatric HospitalUniversity of Geneva School of MedicineGenevaSwitzerland
  2. 2.Fisnberg Research Center for NeurobiologyMount Sinai School of MedicineNew YorkUSA
  3. 3.Department of Geriatrics and Adult DevelopmentMount Sinai School of MedicineNew YorkUSA
  4. 4.Department of Psychiatry, IUPG Bel-AirUniversity of Geneva School of MedicineGenevaSwitzerland

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