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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1998 Aug;65(2):184–190. doi: 10.1136/jnnp.65.2.184

Factors affecting the age of onset and rate of progression of Alzheimer's disease

J Bowler 1, D Munoz 1, H Merskey 1, V Hachinski 1
PMCID: PMC2170212  PMID: 9703168

Abstract

OBJECTIVES—To assess the role of cerebrovascular disease, sex, education, occupation, year of birth, leukoaraiosis, congophilic angiopathy, family history, and other demographic factors on the reported age of onset and rate of progression of Alzheimer's disease.
METHODS—Analysis of data from the University of Western Ontario Dementia Study, a prospective longitudinal study of dementia patients with clinical and 6 monthly psychometric follow up to postmortem based in a university memory disorders clinic with secondary and tertiary referrals. There were 172 patients with dementia. The main outcome measures were the reported age of onset of cognitive decline as described by the family (available in 168) and rate of progression as measured during the linear phase of the extended scale for dementia, which could be calculated in 66. The cases subdivided into 49 cases of definite Alzheimer's disease without infarcts, 25 cases of otherwise definite Alzheimer's disease with infarcts, 79 cases of probable Alzheimer's disease without infarcts, and 19 such cases with infarcts.
RESULTS—The age of onset was not influenced by the rate of progression, the presence of cerebral infarcts, or congophilic angiopathy. Educational level, occupational level, sex, family history, year of birth, reported age of onset, severity at entry, an ischaemic score, and the presence of leukoariosis, affected neither age of onset nor the rate of progression. An earlier year of birth had a major effect and higher education had a minor effect on earlier age of onset. The earlier the year of birth, the lower the educational level and the greater the accrual of cerebral infarcts.
CONCLUSIONS—Contrary to series without pathological verification, age of onset in this study was not affected by occupation. Education had a modest effect on earlier reported onset, probably reflecting earlier recognition. As birth year has a strong effect on educational level and the occurrence of cerebral infarcts, this must be taken into account when analysing for risk factors for Alzheimer's disease.



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Selected References

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  1. Beard C. M., Kokmen E., Offord K. P., Kurland L. T. Lack of association between Alzheimer's disease and education, occupation, marital status, or living arrangement. Neurology. 1992 Nov;42(11):2063–2068. doi: 10.1212/wnl.42.11.2063. [DOI] [PubMed] [Google Scholar]
  2. Berg L., Miller J. P., Storandt M., Duchek J., Morris J. C., Rubin E. H., Burke W. J., Coben L. A. Mild senile dementia of the Alzheimer type: 2. Longitudinal assessment. Ann Neurol. 1988 May;23(5):477–484. doi: 10.1002/ana.410230509. [DOI] [PubMed] [Google Scholar]
  3. Boller F., Becker J. T., Holland A. L., Forbes M. M., Hood P. C., McGonigle-Gibson K. L. Predictors of decline in Alzheimer's disease. Cortex. 1991 Mar;27(1):9–17. doi: 10.1016/s0010-9452(13)80264-x. [DOI] [PubMed] [Google Scholar]
  4. Bonaiuto S., Rocca W. A., Lippi A., Giannandrea E., Mele M., Cavarzeran F., Amaducci L. Education and occupation as risk factors for dementia: a population-based case-control study. Neuroepidemiology. 1995;14(3):101–109. doi: 10.1159/000109785. [DOI] [PubMed] [Google Scholar]
  5. Bowler J. V., Munoz D. G., Merskey H., Hachinski V. Fallacies in the pathological confirmation of the diagnosis of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 1998 Jan;64(1):18–24. doi: 10.1136/jnnp.64.1.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Breitner J. C., Gau B. A., Welsh K. A., Plassman B. L., McDonald W. M., Helms M. J., Anthony J. C. Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study. Neurology. 1994 Feb;44(2):227–232. doi: 10.1212/wnl.44.2.227. [DOI] [PubMed] [Google Scholar]
  7. Brooks J. O., 3rd, Kraemer H. C., Tanke E. D., Yesavage J. A. The methodology of studying decline in Alzheimer's disease. J Am Geriatr Soc. 1993 Jun;41(6):623–628. doi: 10.1111/j.1532-5415.1993.tb06734.x. [DOI] [PubMed] [Google Scholar]
  8. Brun A., Gustafson L., Englund E. Subcortical pathology of Alzheimer's disease. Adv Neurol. 1990;51:73–77. [PubMed] [Google Scholar]
  9. Burns A., Jacoby R., Levy R. Progression of cognitive impairment in Alzheimer's disease. J Am Geriatr Soc. 1991 Jan;39(1):39–45. doi: 10.1111/j.1532-5415.1991.tb05904.x. [DOI] [PubMed] [Google Scholar]
  10. Callahan C. M., Hall K. S., Hui S. L., Musick B. S., Unverzagt F. W., Hendrie H. C. Relationship of age, education, and occupation with dementia among a community-based sample of African Americans. Arch Neurol. 1996 Feb;53(2):134–140. doi: 10.1001/archneur.1996.00550020038013. [DOI] [PubMed] [Google Scholar]
  11. Chimowitz M. I., Awad I. A., Furlan A. J. Periventricular lesions on MRI. Facts and theories. Stroke. 1989 Jul;20(7):963–967. doi: 10.1161/01.str.20.7.963. [DOI] [PubMed] [Google Scholar]
  12. Cobb J. L., Wolf P. A., Au R., White R., D'Agostino R. B. The effect of education on the incidence of dementia and Alzheimer's disease in the Framingham Study. Neurology. 1995 Sep;45(9):1707–1712. doi: 10.1212/wnl.45.9.1707. [DOI] [PubMed] [Google Scholar]
  13. Duara R., Barker W. W., Lopez-Alberola R., Loewenstein D. A., Grau L. B., Gilchrist D., Sevush S., St George-Hyslop S. Alzheimer's disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset. Neurology. 1996 Jun;46(6):1575–1579. doi: 10.1212/wnl.46.6.1575. [DOI] [PubMed] [Google Scholar]
  14. Duara R., Lopez-Alberola R. F., Barker W. W., Loewenstein D. A., Zatinsky M., Eisdorfer C. E., Weinberg G. B. A comparison of familial and sporadic Alzheimer's disease. Neurology. 1993 Jul;43(7):1377–1384. doi: 10.1212/wnl.43.7.1377. [DOI] [PubMed] [Google Scholar]
  15. Ebly E. M., Parhad I. M., Hogan D. B., Fung T. S. Prevalence and types of dementia in the very old: results from the Canadian Study of Health and Aging. Neurology. 1994 Sep;44(9):1593–1600. doi: 10.1212/wnl.44.9.1593. [DOI] [PubMed] [Google Scholar]
  16. Escobar J. I., Burnam A., Karno M., Forsythe A., Landsverk J., Golding J. M. Use of the Mini-Mental State Examination (MMSE) in a community population of mixed ethnicity. Cultural and linguistic artifacts. J Nerv Ment Dis. 1986 Oct;174(10):607–614. doi: 10.1097/00005053-198610000-00005. [DOI] [PubMed] [Google Scholar]
  17. Fillenbaum G. G., Hughes D. C., Heyman A., George L. K., Blazer D. G. Relationship of health and demographic characteristics to Mini-Mental State examination score among community residents. Psychol Med. 1988 Aug;18(3):719–726. doi: 10.1017/s0033291700008412. [DOI] [PubMed] [Google Scholar]
  18. Gearing M., Mirra S. S., Hedreen J. C., Sumi S. M., Hansen L. A., Heyman A. 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 Mar;45(3 Pt 1):461–466. doi: 10.1212/wnl.45.3.461. [DOI] [PubMed] [Google Scholar]
  19. Hachinski V. C., Potter P., Merskey H. Leuko-araiosis. Arch Neurol. 1987 Jan;44(1):21–23. doi: 10.1001/archneur.1987.00520130013009. [DOI] [PubMed] [Google Scholar]
  20. Haupt M., Pollmann S., Kurz A. Symptom progression in Alzheimer's disease: relation to onset age and familial aggregation. Results of a longitudinal study. Acta Neurol Scand. 1993 Nov;88(5):349–353. doi: 10.1111/j.1600-0404.1993.tb05356.x. [DOI] [PubMed] [Google Scholar]
  21. Hawkins W. E., Duncan D. F., McDermott R. J. A health assessment of older Americans: some multidimensional measures. Prev Med. 1988 May;17(3):344–356. doi: 10.1016/0091-7435(88)90009-6. [DOI] [PubMed] [Google Scholar]
  22. Helmes E., Merskey H., Fox H., Fry R. N., Bowler J. V., Hachinski V. C. Patterns of deterioration in senile dementia of the Alzheimer type. Arch Neurol. 1995 Mar;52(3):306–310. doi: 10.1001/archneur.1995.00540270102026. [DOI] [PubMed] [Google Scholar]
  23. Helmes E., Merskey H., Hachinski V. C., Wands K. An examination of psychometric properties of the extended scale for dementia in three different populations. Alzheimer Dis Assoc Disord. 1992 Winter;6(4):236–246. doi: 10.1097/00002093-199206040-00005. [DOI] [PubMed] [Google Scholar]
  24. Hersch E. L. Development and application of the extended scale for dementia. J Am Geriatr Soc. 1979 Aug;27(8):348–354. doi: 10.1111/j.1532-5415.1979.tb06056.x. [DOI] [PubMed] [Google Scholar]
  25. Hier D. B., Warach J. D., Gorelick P. B., Thomas J. Predictors of survival in clinically diagnosed Alzheimer's disease and multi-infarct dementia. Arch Neurol. 1989 Nov;46(11):1213–1216. doi: 10.1001/archneur.1989.00520470073030. [DOI] [PubMed] [Google Scholar]
  26. Huff F. J., Growdon J. H., Corkin S., Rosen T. J. Age at onset and rate of progression of Alzheimer's disease. J Am Geriatr Soc. 1987 Jan;35(1):27–30. doi: 10.1111/j.1532-5415.1987.tb01315.x. [DOI] [PubMed] [Google Scholar]
  27. Jacobs D., Sano M., Marder K., Bell K., Bylsma F., Lafleche G., Albert M., Brandt J., Stern Y. Age at onset of Alzheimer's disease: relation to pattern of cognitive dysfunction and rate of decline. Neurology. 1994 Jul;44(7):1215–1220. doi: 10.1212/wnl.44.7.1215. [DOI] [PubMed] [Google Scholar]
  28. Jorm A. F., Scott R., Henderson A. S., Kay D. W. Educational level differences on the Mini-Mental State: the role of test bias. Psychol Med. 1988 Aug;18(3):727–731. doi: 10.1017/s0033291700008424. [DOI] [PubMed] [Google Scholar]
  29. Katzman R., Brown T., Thal L. J., Fuld P. A., Aronson M., Butters N., Klauber M. R., Wiederholt W., Pay M., Xiong R. B. Comparison of rate of annual change of mental status score in four independent studies of patients with Alzheimer's disease. Ann Neurol. 1988 Sep;24(3):384–389. doi: 10.1002/ana.410240306. [DOI] [PubMed] [Google Scholar]
  30. Katzman R. Education and the prevalence of dementia and Alzheimer's disease. Neurology. 1993 Jan;43(1):13–20. doi: 10.1212/wnl.43.1_part_1.13. [DOI] [PubMed] [Google Scholar]
  31. Kobari M., Meyer J. S., Ichijo M. Leuko-araiosis, cerebral atrophy, and cerebral perfusion in normal aging. Arch Neurol. 1990 Feb;47(2):161–165. doi: 10.1001/archneur.1990.00530020061017. [DOI] [PubMed] [Google Scholar]
  32. Koss E., Edland S., Fillenbaum G., Mohs R., Clark C., Galasko D., Morris J. C. Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer's disease: A CERAD analysis, Part XII. Neurology. 1996 Jan;46(1):136–141. doi: 10.1212/wnl.46.1.136. [DOI] [PubMed] [Google Scholar]
  33. Kramer-Ginsberg E., Mohs R. C., Aryan M., Lobel D., Silverman J., Davidson M., Davis K. L. Clinical predictors of course for Alzheimer patients in a longitudinal study: a preliminary report. Psychopharmacol Bull. 1988;24(3):458–462. [PubMed] [Google Scholar]
  34. Lau C., Wands K., Merskey H., Boniferro M., Carriere L., Fox H., Hachinski V. C. Sensitivity and specificity of the extended scale for dementia. Arch Neurol. 1988 Aug;45(8):849–852. doi: 10.1001/archneur.1988.00520320035012. [DOI] [PubMed] [Google Scholar]
  35. McGeer P. L., Schulzer M., McGeer E. G. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology. 1996 Aug;47(2):425–432. doi: 10.1212/wnl.47.2.425. [DOI] [PubMed] [Google Scholar]
  36. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E. M. 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. 1984 Jul;34(7):939–944. doi: 10.1212/wnl.34.7.939. [DOI] [PubMed] [Google Scholar]
  37. McLeod J. D., Kessler R. C., Landis K. R. Speed of recovery from major depressive episodes in a community sample of married men and women. J Abnorm Psychol. 1992 May;101(2):277–286. doi: 10.1037//0021-843x.101.2.277. [DOI] [PubMed] [Google Scholar]
  38. Mirra S. S., Heyman A., McKeel D., Sumi S. M., Crain B. J., Brownlee L. M., Vogel F. S., Hughes J. P., van Belle G., Berg L. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology. 1991 Apr;41(4):479–486. doi: 10.1212/wnl.41.4.479. [DOI] [PubMed] [Google Scholar]
  39. Moritz D. J., Petitti D. B. Association of education with reported age of onset and severity of Alzheimer's disease at presentation: implications for the use of clinical samples. Am J Epidemiol. 1993 Feb 15;137(4):456–462. doi: 10.1093/oxfordjournals.aje.a116694. [DOI] [PubMed] [Google Scholar]
  40. Morris J. C., Edland S., Clark C., Galasko D., Koss E., Mohs R., van Belle G., Fillenbaum G., Heyman A. The consortium to establish a registry for Alzheimer's disease (CERAD). Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer's disease. Neurology. 1993 Dec;43(12):2457–2465. doi: 10.1212/wnl.43.12.2457. [DOI] [PubMed] [Google Scholar]
  41. O'Connor D. W., Pollitt P. A., Hyde J. B., Fellows J. L., Miller N. D., Brook C. P., Reiss B. B., Roth M. The prevalence of dementia as measured by the Cambridge Mental Disorders of the Elderly Examination. Acta Psychiatr Scand. 1989 Feb;79(2):190–198. doi: 10.1111/j.1600-0447.1989.tb08587.x. [DOI] [PubMed] [Google Scholar]
  42. O'Connor D. W., Pollitt P. A., Hyde J. B., Fellows J. L., Miller N. D., Brook C. P., Reiss B. B. The reliability and validity of the Mini-Mental State in a British community survey. J Psychiatr Res. 1989;23(1):87–96. doi: 10.1016/0022-3956(89)90021-6. [DOI] [PubMed] [Google Scholar]
  43. O'Connor D. W., Pollitt P. A., Treasure F. P., Brook C. P., Reiss B. B. The influence of education, social class and sex on Mini-Mental State scores. Psychol Med. 1989 Aug;19(3):771–776. doi: 10.1017/s0033291700024375. [DOI] [PubMed] [Google Scholar]
  44. O'Connor D. W., Pollitt P. A., Treasure F. P. The influence of education and social class on the diagnosis of dementia in a community population. Psychol Med. 1991 Feb;21(1):219–224. doi: 10.1017/s003329170001480x. [DOI] [PubMed] [Google Scholar]
  45. Ortof E., Crystal H. A. Rate of progression of Alzheimer's disease. J Am Geriatr Soc. 1989 Jun;37(6):511–514. doi: 10.1111/j.1532-5415.1989.tb05681.x. [DOI] [PubMed] [Google Scholar]
  46. Ott A., Breteler M. M., van Harskamp F., Claus J. J., van der Cammen T. J., Grobbee D. E., Hofman A. Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study. BMJ. 1995 Apr 15;310(6985):970–973. doi: 10.1136/bmj.310.6985.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Peterson B. Re: "Association of education with reported age of onset and severity of Alzheimer's disease at presentation: implications for the use of clinical samples". Am J Epidemiol. 1996 Jun 1;143(11):1177–1177. doi: 10.1093/oxfordjournals.aje.a008700. [DOI] [PubMed] [Google Scholar]
  48. Rich J. B., Rasmusson D. X., Folstein M. F., Carson K. A., Kawas C., Brandt J. Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology. 1995 Jan;45(1):51–55. doi: 10.1212/wnl.45.1.51. [DOI] [PubMed] [Google Scholar]
  49. Rocca W. A., Bonaiuto S., Lippi A., Luciani P., Turtù F., Cavarzeran F., Amaducci L. Prevalence of clinically diagnosed Alzheimer's disease and other dementing disorders: a door-to-door survey in Appignano, Macerata Province, Italy. Neurology. 1990 Apr;40(4):626–631. doi: 10.1212/wnl.40.4.626. [DOI] [PubMed] [Google Scholar]
  50. Scheltens P., Barkhof F., Valk J., Algra P. R., van der Hoop R. G., Nauta J., Wolters E. C. White matter lesions on magnetic resonance imaging in clinically diagnosed Alzheimer's disease. Evidence for heterogeneity. Brain. 1992 Jun;115(Pt 3):735–748. doi: 10.1093/brain/115.3.735. [DOI] [PubMed] [Google Scholar]
  51. Skoog I., Nilsson L., Palmertz B., Andreasson L. A., Svanborg A. A population-based study of dementia in 85-year-olds. N Engl J Med. 1993 Jan 21;328(3):153–158. doi: 10.1056/NEJM199301213280301. [DOI] [PubMed] [Google Scholar]
  52. Skoog I., Palmertz B., Andreasson L. A. The prevalence of white-matter lesions on computed tomography of the brain in demented and nondemented 85-year-olds. J Geriatr Psychiatry Neurol. 1994 Jul-Sep;7(3):169–175. doi: 10.1177/089198879400700308. [DOI] [PubMed] [Google Scholar]
  53. Stern R. G., Mohs R. C., Bierer L. M., Silverman J. M., Schmeidler J., Davidson M., Davis K. L. Deterioration on the Blessed test in Alzheimer's disease: longitudinal data and their implications for clinical trials and identification of subtypes. Psychiatry Res. 1992 May;42(2):101–110. doi: 10.1016/0165-1781(92)90074-d. [DOI] [PubMed] [Google Scholar]
  54. Stern R. G., Mohs R. C., Davidson M., Schmeidler J., Silverman J., Kramer-Ginsberg E., Searcey T., Bierer L., Davis K. L. A longitudinal study of Alzheimer's disease: measurement, rate, and predictors of cognitive deterioration. Am J Psychiatry. 1994 Mar;151(3):390–396. doi: 10.1176/ajp.151.3.390. [DOI] [PubMed] [Google Scholar]
  55. Stern Y., Alexander G. E., Prohovnik I., Mayeux R. Inverse relationship between education and parietotemporal perfusion deficit in Alzheimer's disease. Ann Neurol. 1992 Sep;32(3):371–375. doi: 10.1002/ana.410320311. [DOI] [PubMed] [Google Scholar]
  56. Stern Y., Alexander G. E., Prohovnik I., Stricks L., Link B., Lennon M. C., Mayeux R. Relationship between lifetime occupation and parietal flow: implications for a reserve against Alzheimer's disease pathology. Neurology. 1995 Jan;45(1):55–60. doi: 10.1212/wnl.45.1.55. [DOI] [PubMed] [Google Scholar]
  57. Stern Y., Gurland B., Tatemichi T. K., Tang M. X., Wilder D., Mayeux R. Influence of education and occupation on the incidence of Alzheimer's disease. JAMA. 1994 Apr 6;271(13):1004–1010. [PubMed] [Google Scholar]
  58. Sulkava R., Wikström J., Aromaa A., Raitasalo R., Lehtinen V., Lahtela K., Palo J. Prevalence of severe dementia in Finland. Neurology. 1985 Jul;35(7):1025–1029. doi: 10.1212/wnl.35.7.1025. [DOI] [PubMed] [Google Scholar]
  59. Wade J. P., Mirsen T. R., Hachinski V. C., Fisman M., Lau C., Merskey H. The clinical diagnosis of Alzheimer's disease. Arch Neurol. 1987 Jan;44(1):24–29. doi: 10.1001/archneur.1987.00520130016010. [DOI] [PubMed] [Google Scholar]
  60. Zhang M. Y., Katzman R., Salmon D., Jin H., Cai G. J., Wang Z. Y., Qu G. Y., Grant I., Yu E., Levy P. The prevalence of dementia and Alzheimer's disease in Shanghai, China: impact of age, gender, and education. Ann Neurol. 1990 Apr;27(4):428–437. doi: 10.1002/ana.410270412. [DOI] [PubMed] [Google Scholar]
  61. Zigmond A. S., Snaith R. P. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x. [DOI] [PubMed] [Google Scholar]

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