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Risk factors and early signs of Alzheimer's disease in a family study sample

Risk of AD

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Abstract

Objective

Several predictors of Alzheimer's disease (AD) have been identified. However, the relevance and independent contribution of risk factors and of possible early signs such as mild cognitive impairment and subjective memory impairment on the development of AD has not been investigated prospectively in a cohort of non–demented elderly including first–degree relatives of AD subjects.

Method

The development of AD was investigated in 757 non–demented elderly. Initial diagnoses were made from personal interviews. Information on 633 subjects after 4.7 ± 1.2 years (mean ± SD) was obtained either from personal or family history interviews. Using forward logistic regression analysis, predictors were identified by comparing their presence in 38 subjects who developed AD and 577 subjects who remained non–demented.

Results

The most important predictors of later Alzheimer's disease were increased age (Odds ratio OR = 1.086/additional year, p < 0.001), initial subjective memory complaints (OR = 2.68, p = 0.019), initial mild cognitive impairment (OR = 2.51, p = 0.032) and female gender (OR = 2.84, p = 0.069). Exploratory analysis revealed that previous depression after the age of 60 years (OR = 2.37, p = 0.033) and the presence of the apolipoprotein E4 allele (OR = 2.49, p = 0.043) individually predicted new AD during follow–up. A positive family history of AD (i. e. being a first degree relative of a subject suffering from AD) did not significantly influence the development of AD (p > 0.2).

Conclusions

Increased age, the presence of mild cognitive impairment, subjective memory impairment and gender are the most relevant independent predictors of later Alzheimer's disease that may be used in combination for clinical prediction of AD.

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References

  1. Albert MS (1996) Cognitive and neurobiology markers of early Alzheimer disease. Proc Natl Acad Sci USA 93:13547–13551

    Article  CAS  PubMed  Google Scholar 

  2. Almkvist O, Basun H, Bäckman L, Herlitz A, Lannfelt L, Small B, Viitanen M, Wahlund LO, Winblad B (1998) Mild cognitive impairment – an early stage of Alzheimer's disease? J Neural Transm 54(Suppl):21–29

    CAS  Google Scholar 

  3. American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised. Washington, DC: American Psychiatric Association

  4. Andersen K, Launer LJ, Dewey ME, Letenneur L, Ott A, Copeland JR, Dartigues JF, Kragh–Sorensen P, Baldereschi M, Brayne C, Lobo A, Martinez–Lage JM, Stijnen T, Hofman A (1999a) Gender differences in the incidence of AD and vascular dementia: The EURODEM Studies. EURODEM Incidence Research Group. Neurology 53:1992–1997

    CAS  Google Scholar 

  5. Andersen K, Nielsen H, Lolk A, Andersen J, Becker I, Kragh– Sorensen P (1999b) Incidence of very mild to severe dementia and Alzheimer's disease in Denmark: the Odense Study. Neurology 52:85–90

    CAS  Google Scholar 

  6. Andreasen NC, Endicott J, Spitzer RL, Winokur G (1977) The family history method using diagnostic criteria. Reliability and validity. Arch Gen Psychiatry 34:1229–1235

    CAS  PubMed  Google Scholar 

  7. Anthony JC, LeResche L, Niaz U, von Korff MR, Folstein MF (1982) Limits of the 'Mini–Mental State' as a screening test for dementia and delirium among hospital patients. Psychol Med 12:397–408

    CAS  PubMed  Google Scholar 

  8. Bartres–Faz D, Junque C, Lopez–Alomar A, Valveny N, Moral P, Casamayor R, Salido A, Bel C, Clemente IC (2001) Neuropsychological and genetic differences between age–associated memory impairment and mild cognitive impairment entities. J Am Geriatr Soc 49:985–990

    CAS  PubMed  Google Scholar 

  9. Berger AK, Fratiglioni L, Forsell Y, Winblad B, Backman L (1999) The occurrence of depressive symptoms in the preclinical phase of AD: a population–based study. Neurology 53:1998–2002

    CAS  PubMed  Google Scholar 

  10. Blessed G, Black SE, Butler T, Kay DW (1991) The diagnosis of dementia in the elderly. A comparison of CAMCOG (the cognitive section of CAMDEX), the AGECAT program, DSM–III, the Mini– Mental State Examination and some short rating scales. Br J Psychiatry 159:193–198

    CAS  PubMed  Google Scholar 

  11. Bondi MW, Salmon DP, Galasko D, Thomas RG, Thal LJ (1999) Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease. Psychol Aging 14:295–303

    Article  CAS  PubMed  Google Scholar 

  12. Bozoki A, Giordani B, Heidebrink JL, Berent S, Foster NL (2001) Related Articles. Mild cognitive impairments predict dementia in nondemented elderly patients with memory loss. Arch Neurol 58:411–416

    Article  CAS  PubMed  Google Scholar 

  13. Breitner JCS, Folstein MF (1984) Familial Alzheimer Dementia: a prevalent disorder with specific clinical features. Psychol Med 14:63–80

    CAS  PubMed  Google Scholar 

  14. Carr DB, Gray S, Baty J, Morris JC (2000) The value of informant versus individual's complaints of memory impairment in early dementia. Neurology 55:1724–1726

    CAS  PubMed  Google Scholar 

  15. Chen P, Ganguli M, Mulsant BH, De Kosky ST (1999) The temporal relationship between depressive symptoms and dementia: a community–based prospective study. Arch Gen Psychiatry 56:261–266

    CAS  PubMed  Google Scholar 

  16. Clarke M, Jagger C, Anderson J, Battcock T, Kelly F, Stern MC (1991) The prevalence of dementia in a total population: a comparison of two screening instruments. Age Ageing 20:396–403

    CAS  PubMed  Google Scholar 

  17. Copeland JR, McCracken CF, Dewey ME, Wilson KC, Doran M, Gilmore C, Scott A, Larkin BA (1999) Undifferentiated dementia, Alzheimer's disease and vascular dementia: age– and gender–related incidence in Liverpool. The MRC–ALPHA Study. Br J Psychiatry 175:433–438

    CAS  PubMed  Google Scholar 

  18. Daly E, Zaitchik D, Copeland M, Schmahmann J, Gunther J, Albert M (2000) Predicting conversion to Alzheimer disease using standardized clinical information. Arch Neurol 57:675–680

    Article  CAS  PubMed  Google Scholar 

  19. Devanand DP, Folz M, Gorlyn M, Moeller JR, Stern Y (1997) Questionable dementia: clinical course and predictors of outcome. J Am Geriatr Soc 45:321–328

    CAS  PubMed  Google Scholar 

  20. Doody RS, Massman P, Dunn JK (2001) A method for estimating progression rates in Alzheimer disease. Arch Neurol 58:449–454

    CAS  PubMed  Google Scholar 

  21. Doran M, Larner AJ (2004) Prominent behavioural and psychiatric symptoms in early–onset Alzheimer's disease in a sib pair with the presenilin–1 gene R269G mutation. Eur Arch Psychiatry Clin Neurosci 254(3):187–189

    CAS  PubMed  Google Scholar 

  22. Flicker C, Ferris SH, Reisberg B (1991) Mild cognitive impairment in the elderly: predictors of dementia. Neurology 41:1006–1009

    CAS  PubMed  Google Scholar 

  23. Folstein MF, Folstein SE, McHugh PR (1975) "Mini–Mental State". A practical method for grading the cognitive state of patients for the clinician. J Psychiat Res 12:189–198

    CAS  PubMed  Google Scholar 

  24. Fratiglioni L, Viitanen M, von Strauss E, Tontodonati V, Herlitz A, Winblad B (1997) Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm. Neurology 48:132–138

    CAS  PubMed  Google Scholar 

  25. Gao S, Hendrie HC, Hall KS, Hui S (1998) The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta–analysis. Arch Gen Psychiatry 55:809–815

    CAS  PubMed  Google Scholar 

  26. Geerlings MI, Jonker C, Bouter LM, Ader HJ, Schmand B (1999) Association between memory complaints and incident Alzheimer's disease in elderly people with normal baseline cognition. Am J Psychiatry 156:531–537

    CAS  PubMed  Google Scholar 

  27. Geerlings MI, Schoevers RA, Beekman AT, Jonker C, Deeg DJ, Schmand B, Ader HJ, Bouter LM, Van Tilburg W (2000) Depression and risk of cognitive decline and Alzheimer's disease. Results of two prospective community–based studies in the Netherlands. Br J Psychiatry 176:568–575

    Article  CAS  PubMed  Google Scholar 

  28. Gomez–Isla T, West HL, Rebeck GW, Harr SD, Growdon JH, Locascio JJ, Perls TT, Lipsitz LA, Hyman BT (1996) Clinical and pathological correlates of apolipoprotein E epsilon 4 in Alzheimer's disease. Ann Neurol 39:62–70

    CAS  PubMed  Google Scholar 

  29. Grut M, Fratiglioni L, Viitanen M, Winblad B (1993) Accuracy of the Mini–Mental Status Examination as a screening test for dementia in a Swedish elderly population. Acta Neurol Scand 87:312–317

    CAS  PubMed  Google Scholar 

  30. Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, Symon L (1975) Cerebral blood flow in dementia. Arch Neurol 32:632–637

    CAS  PubMed  Google Scholar 

  31. Hampel H, Haslinger A, Scheloske M, Padberg F, Fischer P, Unger J, Teipel SJ, Neumann M, Rosenberg C, Oshida R, Hulette C, Pongratz D, Ewers M, Kretzschmar HA, Moller HJ (2004) Pattern of interleukin–6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer's disease brain. Eur Arch Psychiatry Clin Neurosci 26:(Epub ahead of print)

  32. Hebert LE, Scherr PA, McCann JJ, Beckett LA, Evans DA (2001) Is the risk of developing Alzheimer's disease greater for women than for men? Am J Epidemiol 153:132–136

    Article  CAS  PubMed  Google Scholar 

  33. Heun R, Burkart M, Maier W (1995) Selection biases during recruitment of patients and relatives for a family study in the elderly. J Psychiatr Res 29:491–504

    Article  CAS  PubMed  Google Scholar 

  34. Heun R, Maier W, Müller H (1997) Subject and informant variables affecting family history diagnoses of depression and dementia. Psychiatr Res 1:175–180

    Google Scholar 

  35. Heun R, Müller H, Freyberger HJ, Maier W (1998) Reliability of interview information in a family study in the elderly. Soc Psychiatry Psychiatr Epidemiol 33:140–144

    CAS  PubMed  Google Scholar 

  36. Heun R, Müller H (1998) Interinformant reliability of family history information on psychiatric disorders in relatives. Eur Arch Psychiatr Clin Neurosci 248:104–109

    CAS  Google Scholar 

  37. Heun R, Papassotiropoulos A, Jessen F, Maier W, Breitner JCS (2001) A family study on the relationship between Alzheimer's disease, early–onset and late–onset depression in the elderly. Arch Gen Psychiatry 58:190–196

    CAS  PubMed  Google Scholar 

  38. Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31:545–548

    CAS  PubMed  Google Scholar 

  39. Hulette CM, Welsh–Bohmer KA, Murray MG, Saunders AM, Mash DC, McIntyre LM (1998) Neuropathological and neuropsychological changes in “normal” aging: evidence for preclinical Alzheimer disease in cognitively normal individuals. J Neuropathol Exp Neurol 57:1168–1174

    CAS  PubMed  Google Scholar 

  40. Jonker C, Geerlings MI, Schmand B (2000) Are memory complaints predictive for dementia? A review of clinical and population– based studies. Int J Geriatr Psychiatry 15:983–991

    CAS  PubMed  Google Scholar 

  41. Jorm AF, Christensen H, Korten AE, Henderson AS, Jacomb PA, Mackinnon A (1997) Do cognitive complaints either predict future cognitive decline or reflect past cognitive decline? A longitudinal study of an elderly community sample. Psychol Med 27:91–98

    Article  CAS  PubMed  Google Scholar 

  42. Jorm AF, Christensen H, Korten AE, Jacomb PA, Henderson AS (2001) Memory complaints as a precursor of memory impairment in older people: a longitudinal analysis over 7–8 years. Psychol Med 31:441–449

    CAS  PubMed  Google Scholar 

  43. Kawas C, Gray S, Brookmeyer R, Fozard J, Zonderman A (2000) Age–specific incidence rates of Alzheimer's disease: the Baltimore Longitudinal Study of Aging. Neurology 54:2072–2077

    CAS  PubMed  Google Scholar 

  44. Launer LJ, Andersen K, Dewey ME, Letenneur L, Ott A, Amaducci LA, Brayne C, Copeland JRM, Dartiques JF, Kragh–Sorensen P, Lobo A, Martinez–Lage JM, Stijnen T, Hofman A, and the EURODEM Incidence Research Group and Work Groups (1999) Rates and risk factors for dementia and Alzheimer's disease. Results from EURODEM pooled analyses. Neurology 52:78–84

    CAS  PubMed  Google Scholar 

  45. Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM (1982) Best estimate of lifetime psychiatric diagnosis. Arch Gen Psychiatry 39:879–883

    CAS  PubMed  Google Scholar 

  46. Letenneur L, Gilleron V, Commenges D, Helmer C, Orgogozo JM, Dartigues JF (1999) Are sex and educational level independent predictors of dementia and Alzheimer's disease? Incidence data from the PAQUID project. J Neurol Neurosurg Psychiatry 66:177–183

    CAS  PubMed  Google Scholar 

  47. Letenneur L, Launer LJ, Andersen K, Dewey ME, Ott A, Copeland JR, Dartigues JF, Kragh–Sorensen P, Baldereschi M, Brayne C, Lobo A, Martinez–Lage JM, Stijnen T, Hofman A (2000) Education and the risk for Alzheimer's disease: sex makes a difference. EURODEM pooled analyses. EURODEM Incidence Research Group. Am J Epidemiol 151:1064–1071

    CAS  PubMed  Google Scholar 

  48. Mohs RC, Breitner JC, Silverman JM, Davis KL (1987) Alzheimer's disease. Morbid risk among first–degree relatives approximates 50% by 90 years of age. Arch Gen Psychiatry 44:405–408

    CAS  PubMed  Google Scholar 

  49. Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, Rubin EH, Berg L (2001) Mild cognitive impairment represents early–stage Alzheimer disease. Arch Neurol 58:397–405

    CAS  PubMed  Google Scholar 

  50. Murphy GM, Taylor J, Kraemer HC, Yesavage J, Tinklenberg JR (1997) No association between apolipoprotein E epsilon 4 allele and rate of decline in Alzheimer's disease. Am J Psychiatry 154:603–608

    PubMed  Google Scholar 

  51. Payami H, Grimslid H, Oken B, Camicioli R, Sexton G, Dame A, Howieson D, Kaye J (1997) A prospective study of cognitive health in the elderly (Oregon Brain Aging Study): effects of family history and apolipoprotein E genotype. Am J Hum Genet 60:948–956

    CAS  PubMed  Google Scholar 

  52. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Kokmen E, Tangelos EG (1997) Aging, memory, and mild cognitive impairment. Int Psychogeriatr 1(Suppl 9):65–69

    CAS  Google Scholar 

  53. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E (1999) Mild cognitive impairment: clinical characterization and outcome. Arch Neurol 56:303–308

    Article  CAS  PubMed  Google Scholar 

  54. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST (2001) Practice parameter: early detection of dementia: mild cognitive impairment (an evidence–based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56:1133–1142

    CAS  PubMed  Google Scholar 

  55. Ptok U, Seeher C, Jessen F, Papassotiropoulos A, Heun R (2001) Interrater reliability of family history for depression and dementia. European Arch Psychiatry Clin Neurosci 251:279–283

    CAS  Google Scholar 

  56. Ritchie K, Artero S, Touchon J (2001) Classification criteria for mild cognitive impairment: a population–based validation study. Neurology 56:37–42

    CAS  PubMed  Google Scholar 

  57. Rocca WA, Cha RH, Waring SC, Kokmen E (1998) Incidence of dementia and Alzheimer's disease: a reanalysis of data from Rochester, Minnesota, 1975–1984. Am J Epidemiol 148:51–62

    CAS  PubMed  Google Scholar 

  58. Roses AD (1998) Apolipoprotein E and Alzheimer's disease. The tip of the susceptibility iceberg. Ann N Y Acad Sci 855:738–743

    Article  CAS  PubMed  Google Scholar 

  59. Ruitenberg A, Ott A, van Swieten JC, Hofman A, Breteler MM (2001) Incidence of dementia: does gender make a difference? Neurobiol Aging 22:575–580

    Article  CAS  PubMed  Google Scholar 

  60. Schmand B, Jonker C, Geerlings MI, Lindeboom J (1997) Subjective memory complaints in the elderly: depressive symptoms and future dementia. Br J Psychiatry 171:373–376

    CAS  PubMed  Google Scholar 

  61. Schofield PW, Jacobs D, Marder K, Sano M, Stern Y (1997) The validity of new memory complaints in the elderly. Arch Neurol 54:756–759

    CAS  PubMed  Google Scholar 

  62. Seshadri S, Wolf PA, Beiser A, Au R, K, White R, D'Agostino RB (1997) Lifetime risk of dementia and Alzheimer's disease. The impact of mortality on risk estimates in the Framingham Study. Neurology 49:1498–1504

    CAS  PubMed  Google Scholar 

  63. Silverman JM, Breitner JCS, Mohs RC, Davis KL (1986) Reliability of the family history method in genetic studies of Alzheimer's disease and related dementias. Am J Psychiatry 143:1279–1282

    CAS  PubMed  Google Scholar 

  64. Silverman JM, Li G, Zaccario ML, Smith CJ, Schmeidler J, Mohs RC, Davis KL (1994) Patterns of risk in first–degree relatives of patients with Alzheimer's disease. Arch Gen Psychiatry 51:577–586

    CAS  PubMed  Google Scholar 

  65. Silverman JM, Smith CM, Marin DB, Schmeidler J, Birstein S, Lantz M, Davis KL, Mohs RC (2000) Has familial aggregation in Alzheimer's disease been overestimated? Int J Geriatr Psychiatry 15:631–637

    CAS  PubMed  Google Scholar 

  66. Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM, Van Broeckhoven C, van Duijn CM (1998) Risk estimates of dementia by apolipoprotein E genotypes from a population–based incidence study: the Rotterdam Study. Arch Neurol 55:964–968

    Article  CAS  PubMed  Google Scholar 

  67. Small BJ, Viitanen M, Backman L (1997) Mini–Mental State Examination item scores as predictors of Alzheimer's disease: incidence data from the Kungsholmen Project, Stockholm. J Gerontol A Biol Sci Med Sci 52:M299–M304

    CAS  PubMed  Google Scholar 

  68. Small GW, Chen ST, Komo S, Ercoli L, Bookheimer S, Miller K, Lavretsky H, Saxena S, Kaplan A, Dorsey D, Scott WK, Saunders AM, Haines JL, Roses AD, Pericak–Vance MA (1999) Memory self–appraisal in middle–aged and older adults with the apolipoprotein E–4 allele. Am J Psychiatry 156:1035–1038

    CAS  PubMed  Google Scholar 

  69. Small GW, La Rue A, Komo S, Kaplan A, Mandelkern MA (1995) Predictors of cognitive change in middle–aged and older adults with memory loss. Am J Psychiatry 152:1757–1764

    CAS  PubMed  Google Scholar 

  70. Soininen HS, Scheltens P (1998) Early diagnostic indices for the prevention of Alzheimer's disease. Ann Med 30:553–559

    CAS  PubMed  Google Scholar 

  71. Sramek JJ, Veroff AE, Cutler NR (2001) The status of ongoing trials for mild cognitive impairment. Expert Opin Investig Drug 10:741–752

    CAS  Google Scholar 

  72. Steffens DC, Plassman BL, Helms MJ, Welsh–Bohmer KA, Saunders AM, Breitner JC (1997) A twin study of late–onset depression and apolipoprotein E epsilon 4 as risk factors for Alzheimer's disease. Biol Psychiatry 41:851–856

    Article  CAS  PubMed  Google Scholar 

  73. Stewart R, Russ C, Richards M, Brayne C, Lovestone S, Mann A (2001) Depression, APOE genotype and subjective memory impairment: a cross–sectional study in an African–Caribbean population. Psychol Med 31:431–440

    CAS  PubMed  Google Scholar 

  74. Tierney MC, Szalai JP, Dunn E, Geslani D, McDowell I (2000) Prediction of probable Alzheimer disease in patients with symptoms suggestive of memory impairment. Value of the Mini–Mental State Examination. Arch Fam Med 9:527–532

    Article  CAS  PubMed  Google Scholar 

  75. Tierney MC, Szalai JP, Snow WG, Fisher RH, Tsuda T, Chi H, McLachlan DR, St George–Hyslop PH (1996b) A prospective study of the clinical utility of ApoE genotype in the prediction of outcome in patients with memory impairment. Neurology 46:149–154

    CAS  Google Scholar 

  76. Wang PN, Wang SJ, Fuh JL, Teng EL, Liu CY, Lin CH, Shyu HY, Lu SR, Chen CC, Liu HC (2000) Subjective memory complaint in relation to cognitive performance and depression: a longitudinal study of a rural Chinese population. J Am Geriatr Soc 48:295–299

    CAS  PubMed  Google Scholar 

  77. Weiner MF, Vega G, Risser RC, Honig LS, Cullum CM, Crumpacker D, Rosenberg RN (1999) Apolipoprotein E epsilon 4, other risk factors, and course of Alzheimer's disease. Biol Psychiatry 45:633–638

    Article  CAS  PubMed  Google Scholar 

  78. Wetherell JL, Gatz M, Johansson B, Pedersen NL (1999) History of depression and other psychiatric illness as risk factors for Alzheimer disease in a twin sample. Alzheimer Dis Assoc Disord 13:47–52

    CAS  PubMed  Google Scholar 

  79. World Health Organization (1990) Composite International Diagnostic Interview. Geneva: Division of Mental Health, World Health Organization

  80. Zaudig M, Mittelhammer J, Hiller W, Pauls A, Thora C, Morinigo A, Mombour W (1991) SIDAM – A structured interview for the diagnosis of dementia of the Alzheimer type, multi–infarct dementia and dementias of other aetiology according to ICD–10 and DSM–III–R. Psychol Med 21:225–236

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Dept. of Psychiatry, University of Bonn, Venusberg, 53105, Bonn, Germany

    R. Heun MD, PhD, H. Kölsch PhD & F. Jessen MD

  2. Dept. of Old Age Psychiatry, University of Birmingham, Birmingham, UK

    R. Heun MD, PhD

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Heun, ., Kölsch, H. & Jessen, F. Risk factors and early signs of Alzheimer's disease in a family study sample. Eur Arch Psychiatry Clin Neurosci 256, 28–36 (2006). https://doi.org/10.1007/s00406-005-0596-4

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