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Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study

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Abstract

In dementia with Lewy bodies (DLB), the Lewy bodies (LBs) are an essential substrate. Although LB pathology has gained increasing attention as one of the major causes of dementia, little is known about the exact prevalence of LB pathology in the general population. In addition, the pathology of Alzheimer-type dementia (ATD) is frequently associated with DLB. To investigate the prevalence of LB pathology in a community-based population and to evaluate the relationship between LB and ATD pathology, we performed an analysis of 102 consecutive autopsy cases. The survey extended over 2.5 years and autopsy rate was 70.5%. LB pathology was detected using α-synuclein immunohistochemistry and was assessed based on consensus guidelines for DLB. ATD pathology was evaluated by both CERAD and NIA-RI criteria. Twenty-nine subjects were clinically demented. LB pathology was present in 23 (22.5%) of 102 cases, and in 12 (41.4%) of the demented subjects. The LB score was not significantly different between DLB cases and non-demented subjects with LB pathology (nd-LB), while the Braak stages were significantly different between the two groups. Prevalence of LB pathology constantly increased with age. DLB cases accompanying severe ATD pathology showed more rapid increase of LB scores than did DLB cases without severe ATD pathology. Moreover, DLB cases with severe ATD pathology had poorer prognoses than those without severe ATD pathology. Our results suggested that aging and severe ATD pathology have a strong effect on the evolution of LB pathology.

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References

  1. American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, revised. American Psychiatric Association, Washington, DC

  2. Anonymous (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer's disease. The national institute on aging, and Reagan institute working group on diagnostic criteria for the neuropathological assessment of Alzheimer's disease. Neurobiol Aging 18: S1–S2

    Google Scholar 

  3. Arnold SE, Hyman BT, Flory J, Damasio AR, Van Hoesen GW (1991) The topographical distribution of neurofibrillary tangles and neuritic plaque in the cerebral cortex of patients with Alzheimer's disease. Cereb Cortex 1:103–116

    CAS  PubMed  Google Scholar 

  4. Baba H, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T (1998) Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol 152:879–884

    CAS  PubMed  Google Scholar 

  5. Braak H, Braak E (1991) Neuropathological staging of Alzheimer-related changes. Acta Neuropathol 82:239–259

    CAS  PubMed  Google Scholar 

  6. Davis DG, Schmitt FA, Wekstein DR, Markesbery WR (1999) Alzheimer neuropathologic alterations in aged cognitively normal subjects. J Neuropathol Exp Neurol 58:376–388

    CAS  PubMed  Google Scholar 

  7. Del Tredici K, Rüb U, Vos RAI de, Bohl JRE, Braak H (2002) Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 61:413–426

    Google Scholar 

  8. Gibb WR, Less AJ (1988) The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 51:745–752

    CAS  PubMed  Google Scholar 

  9. Gomez-Tortosa E, Newell K, Irizarry MC, Albert M, Growdon JH, Hyman BT (1999) Clinical and quantitative pathological correlates of dementia with Lewy bodies. Neurology 53:1284–1291

    PubMed  Google Scholar 

  10. Hamilton RL (2000) Lewy bodies in Alzheimer's disease: a neuropathological review of 145 cases using α-synuclein immunohistochemistry. Brain Pathol 10:378–394

    PubMed  Google Scholar 

  11. Hansen LA, Masliah E, Galasko D, Terry RD (1993) Plaque-only Alzheimer disease is usually the lewy body variant, and vice versa. J Neuropathol Exp Neurol 52:648–654

    CAS  PubMed  Google Scholar 

  12. Haroutunian V, Serby M, Purohit DP, Perl DP, Marin D, Lantz M, Mohs RC, Davis KL (2000) Contribution of Lewy body inclusions to dementia in patients with and without Alzheimer disease neuropathological conditions. Arch Neurol 57:1145–1150

    CAS  PubMed  Google Scholar 

  13. Heyman A, Fillenbaum GG, Gearing M, Mirra SS, Welsh-Bohmer KA, Peterson B, Pieper C (1999) Comparison of Lewy body variant of Alzheimer's disease with pure Alzheimer' disease: Consortium to Establish a Registry for Alzheimer's Disease, Part XIX. Neurology 52:1839–1844

    CAS  PubMed  Google Scholar 

  14. Hughes AJ, Daniel SE, Blankson S, Lees AJ (1993) A clinicopathologic study of 100 cases of Parkinson's disease. Arch Neurol 50:140–148

    CAS  PubMed  Google Scholar 

  15. Ince PG, McArthur FK, Bjertness E, Torvik A, Candy JM, Edwardson JA (1995) Neuropathological diagnosis in elderly patients in Oslo: Alzheimer's disease, Lewy body disease, vascular lesions. Dementia 6:162–168

    CAS  PubMed  Google Scholar 

  16. Ince PG, Perry EK, Morris CM (1998) Dementia with Lewy bodies. A distinct non-Alzheimer dementia syndrome? Brain Pathol 8:299–324

    Google Scholar 

  17. Iwatubo T, Yamaguchi H, Fujimuro M, Yokosawa H, Ihara Y, Trojanowski JQ, Lee VMY (1996) Purification and characterization of Lewy bodies from the brains of patients with diffuse Lewy body disease. Am J Pathol 148:1517–1529

    Google Scholar 

  18. Jellinger KA, Seppi K, Wenning GK, Poewe W (2002) Impact of coexistent Alzheimer pathology on the natural history of Parkinson's disease. J Neural Transm 109:329–339

    CAS  PubMed  Google Scholar 

  19. Katsuki S (1966) Epidemiological and clinicopathological study on cerebrovascular disease in Japan. Prog Brain Res 21B: 64–89

    Google Scholar 

  20. Kawashima M, Suzuki SO, Doh-ura K, Iwaki T (2000) α-Synuclein is expressed in a variety of brain tumors showing neuronal differentiation. Acta Neuropathol 99:154–160

    CAS  PubMed  Google Scholar 

  21. Kiyohara Y, Yoshitake T, Kato I, Ohmura T, Kawano H, Ueda K, Fujishima M (1994) Changing patterns in the prevalence of dementia in a Japanese community: the Hisayama study. Gerontology 40 (Suppl 2): 29–35

    PubMed  Google Scholar 

  22. Kosaka K, Iseki E (2000) Clinicopathological studies on diffuse Lewy body disease. Neuropathology 20:1–7

    Article  CAS  PubMed  Google Scholar 

  23. Lindboe CF, Hansen HB (1998) The frequency of Lewy bodies in a consecutive autopsy series. Clin Neuropathol 17:204–209

    CAS  PubMed  Google Scholar 

  24. Lippa CF, Fujiwara H, Mann DM, Giasson B, Baba M, Schmidt ML, Nee LE, O'Connell B, Pollen DA, St. George-Hyslop P, Ghetti B, Nochlin D, Bird TD, Cairns NJ, Lee VM, Iwatsubo T, Trojanowski JQ (1998) Lewy bodies contain altered α-synuclein in brains of many familial Alzheimer's disease patients with mutations in presenilin and amyloid precursor protein genes. Am J Pathol 153:1365–1370

    PubMed  Google Scholar 

  25. Lopez OL, Becker JT, Kaufer DI, Hamilton RL, Sweet RA, Klunk W, DeKosky ST (2002) Research evaluation and prospective diagnosis of dementia with Lewy bodies. Arch Neurol 59:43–46

    Article  PubMed  Google Scholar 

  26. 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, Vos RA de, Wilcock GK, Jellinger KA, Perry RH (1996) Consensus guidelines for the clinical and pathological diagnosis of dementia with Lewy bodies (DLB); report of the consortium on DLB international workshop. Neurology 47:1113–1124

    CAS  PubMed  Google Scholar 

  27. McKeith IG, Perry EK, Perry RH (1999) Report of the second dementia with Lewy body international workshop. Diagnosis and treatment. Neurology 53:902–905

    CAS  PubMed  Google Scholar 

  28. 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

    PubMed  Google Scholar 

  29. 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

    CAS  PubMed  Google Scholar 

  30. Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) (2001) Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales. Lancet 357:169–175

    PubMed  Google Scholar 

  31. Olichney JM, Galasko D, Salmon DP, Hofstetter CR, Hansen LA, Katzman R, Thal LJ (1998) Cognitive decline is faster in Lewy body variant than in Alzheimer's disease. Neurology 51:351–357

    CAS  PubMed  Google Scholar 

  32. Parkkinen L, Soininen H, Laakso M, Alafuzoff I (2001) α-Synuclein pathology is highly dependent on the case selection. Neuropathol Appl Neurobiol 27:314–325

    Article  CAS  PubMed  Google Scholar 

  33. Parkkinen L, Soininen H, Alafuzoff I (2003) Regional distribution of α-synuclein pathology in unimpaired aging and Alzheimer disease. J Neuropathol Exp Neurol 62:363–367

    CAS  PubMed  Google Scholar 

  34. Perry RH, Irving D, Tomlinson BE (1990) Lewy body prevalence in the aging brain: relationship to neuropsychiatric disorders, Alzheimer-type pathology and catecholaminergic nuclei. J Neurol Sci 100:223–233

    Article  CAS  PubMed  Google Scholar 

  35. Rinne JO, Rummukainen J, Paljärvi L, Rinne UK (1989) Dementia in Parkinson's disease is related to neuronal loss in the medial substantia nigra. Ann Neurol 26:47–50

    Google Scholar 

  36. Román GC, Tatemichi TK, Erkinjuntti T, et al (1993) Vascular dementia: diagnostic criteria for research stusies. Report of the NINDS-AIREN International Workshop. Neurology 43:250–260

    CAS  PubMed  Google Scholar 

  37. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) α-Synuclein in Lewy bodies. Nature 388:839–840

    CAS  PubMed  Google Scholar 

  38. Tanizaki Y, Kiyohara Y, Kato I, Iwamoto H, Nakayama K, Shinohara N, Arima H, Tanaka K, Ibayashi S, Fujishima M (2000) Incidence and risk factors for subtypes of cerebral infarction in a general population. The Hisayama study. Stroke 31:2616–2622

    CAS  PubMed  Google Scholar 

  39. Van Duinen SG, Lammers GJ, Maat-Schieman MLC, Ross RAC (1999) Numerous and widespread α-synuclein-negative Lewy bodies in an asymptomatic patient. Acta Neurol 97:533–539

    Article  Google Scholar 

  40. Yamazaki M, Arai Y, Baba M, Iwatsubo T, Mori O, Katayama Y, Oyanagi K (2000) α-Synuclein inclusions in amygdala in the brains of patiens with the parkinsonism-dementia complex of Guam. J Neuropathol Exp Neurol 59:585–3591

    PubMed  Google Scholar 

  41. Yoshitake T, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Ohmori S, Nomiyama K, Kawano H, Ueda K, Sueishi K, Tsuneyoshi M, Fujishima M (1995) Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama study. Neurology 45:1161–1168

    CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by the Grant-in-Aid for Scientific Research (Grant-in-Aid for Exploratory research, no. 14657047) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. We are grateful to Dr. Takeshi Iwatsubo (Department of Neuropathology and Neuroscience, University of Tokyo) for generously donating the α-synuclein antibody LB509. We are also grateful to Dr. Shibanosuke Katsuki and Dr. Masatoshi Fujishima, Emeritus Professors of Kyushu University, Dr. Teruo Omae, Emeritus President of the National Cardiovascular Disease Center of Japan, Dr. Yasuo Hirota, Dr. Moriyuki Takeshita, Dr. Kazuo Ueda, Dr. Yutaka Hasuo for their devotion to the Hisayama study.

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  1. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan

    Yoshinobu Wakisaka, Akiko Furuta & Toru Iwaki

  2. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Higashiku, Fukuoka 812-8582, Japan

    Yoshinobu Wakisaka, Yumihiro Tanizaki, Yutaka Kiyohara & Mitsuo Iida

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  1. Yoshinobu Wakisaka
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Correspondence to Yoshinobu Wakisaka.

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Wakisaka, Y., Furuta, A., Tanizaki, Y. et al. Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study. Acta Neuropathol 106, 374–382 (2003). https://doi.org/10.1007/s00401-003-0750-x

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