Genetic susceptibility and head injury as risk factors for Alzheimer's disease among community-dwelling elderly persons and their first-degree relatives
Corresponding Author
Dr. Richard Mayeux MD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Center for Alzheimer's Disease Research
Department of Neurology, College of Physicians and Surgeons, Columbia University
Department of Psychiatry, College of Physicians and Surgeons, Columbia Univeristy
The Gertrude H. Sergievsky Center, 630 West 168th St, Columbia University, New York, NY 10032Search for more papers by this authorRuth Ottman PhD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Division of Epidemiology, Columbia University School of Public Health
Epidemiology of Brain Disorders Research Department, New York State Psychiatric Institute, New York, NY
Search for more papers by this authorMing-Xin Tang PhD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Department of Neurology, College of Physicians and Surgeons, Columbia University
Search for more papers by this authorLourdes Noboa-Bauza MD
Department of Neurology, College of Physicians and Surgeons, Columbia University
Search for more papers by this authorKaren Marder MD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Department of Neurology, College of Physicians and Surgeons, Columbia University
Search for more papers by this authorBarry Gurland MD
Center for Geriatrics and Gerontology, Columbia University School of Public Health
Center for Alzheimer's Disease Research
Department of Psychiatry, College of Physicians and Surgeons, Columbia Univeristy
Search for more papers by this authorYaakov Stern PhD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Center for Alzheimer's Disease Research
Department of Neurology, College of Physicians and Surgeons, Columbia University
Department of Psychiatry, College of Physicians and Surgeons, Columbia Univeristy
Search for more papers by this authorCorresponding Author
Dr. Richard Mayeux MD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Center for Alzheimer's Disease Research
Department of Neurology, College of Physicians and Surgeons, Columbia University
Department of Psychiatry, College of Physicians and Surgeons, Columbia Univeristy
The Gertrude H. Sergievsky Center, 630 West 168th St, Columbia University, New York, NY 10032Search for more papers by this authorRuth Ottman PhD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Division of Epidemiology, Columbia University School of Public Health
Epidemiology of Brain Disorders Research Department, New York State Psychiatric Institute, New York, NY
Search for more papers by this authorMing-Xin Tang PhD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Department of Neurology, College of Physicians and Surgeons, Columbia University
Search for more papers by this authorLourdes Noboa-Bauza MD
Department of Neurology, College of Physicians and Surgeons, Columbia University
Search for more papers by this authorKaren Marder MD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Department of Neurology, College of Physicians and Surgeons, Columbia University
Search for more papers by this authorBarry Gurland MD
Center for Geriatrics and Gerontology, Columbia University School of Public Health
Center for Alzheimer's Disease Research
Department of Psychiatry, College of Physicians and Surgeons, Columbia Univeristy
Search for more papers by this authorYaakov Stern PhD
Gertrude H. Sergievsky Center, Columbia University School of Public Health
Center for Alzheimer's Disease Research
Department of Neurology, College of Physicians and Surgeons, Columbia University
Department of Psychiatry, College of Physicians and Surgeons, Columbia Univeristy
Search for more papers by this authorAbstract
We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease(AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4–9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1–5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3–14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5–18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.
References
- 1 Yanker BA, Mesulam M-M. Beta amyloid and the pathogenesis of Alzheimer's disease. N Engl J Med 1991; 26: 1849–1855
- 2 Selkoe DJ. In the beginning. Nature 1991; 354: 432–433
- 3 Breitner J C S, Silverman JM, Mohs RC, et al. Familial aggregation in Alzheimer's disease: comparison of risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations. Neurology 1988; 38: 207–212
- 4 Huff FJ, Auerbach BA, Charkravarti A, et al. Risk of dementia in relative of patients with Alzheimer's disease. Neurology 1988; 38: 786–790
- 5 Mayeux R, Sano M, Chen J, et al. Risk of dementia in first degree relatives of patients with Alzheimer's disease and related disorders. Arch Neurol 1991; 48: 269–273
- 6 Cook RH, Ward BE, Austin JH. Studies in aging of the brain: IV. Familial Alzheimer's disease: relation to transmissible dementia, aneuploidy, and microtubular defects. Neurology 1979; 29: 1402–1412
- 7 Goudsmit J, White BJ, Weitkamp LR. Familial Alzheimer's disease in two kindred of the same geographic and ethnic origin. J Neurol Sci 1981; 49: 79–89
- 8 Nee LE, Polinsky RJ, Eldridge R, et al. A family with histologically confirmed Alzheimer's disease. Arch Neurol 1983; 40: 203–207
- 9 Bird T, Lampe TH, Nemens RN, et al. Familial Alzheimer's disease in American descendants of the Volga Germans: probable genetic founder effect. Ann Neurol 1988; 23: 25–31
- 10 Bird TD, Sumi SM, Nemens EJ, et al. Phenotypic heterogeneity in familial Alzheimer's disease: a study of 24 kindred. Ann Neurol 1989; 25: 12–25
- 11 Farrer L, Meyers RH, Cupples LA, et al. Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity. Neurology 1990; 40: 395–403
- 12 St. George-Hyslop PH, Tanzi RE, Polinsky RJ, et al. The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science 1987; 235: 885–890
- 13 St. George-Hyslop PH, Haines JL, Farrer LA, et al. Genetic linkage studies suggest Alzheimer's disease is not a simple homogenous disorder. Nature 1990; 347: 194–196
- 14 Pericak-Vance MA, Bebout JL, Gaskell PC, et al. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet 1991; 48: 1034–1050
- 15 Goate A, Chartier-Harlin M-C, Mullan M, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991; 349: 704–706
- 16 Naruse S, Igarashi S, Kobayashi H, et al. Mis-sense mutation Val-to-Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet 1991; 337: 1342–1343
- 17 Lucotte G, Berriche S, David F. Alzheimer's mutation. Nature 1991; 351: 350
- 18 Murrell J, Farlow M, Ghetti B, Benson MD. A mutation in the amyloid protein associated with hereditary Alzheimer's disease. Science 1991; 254: 97–99
- 19 Chartier-Harlin M-C, Crawford F, Houlden H, et al. Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature 1991; 353: 844–846
- 20 Roberts GW, Gentleman SM, Lynch A, Graham DI. Beta A4 amyloid protein deposition in brain after head trauma. Lancet 1991; 338: 1422–1433
- 21 Clinton J, Ambler MW, Roberts GW. Post-traumatic Alzheimer's disease: preponderance of a single plaque type. Neuropathol Appl Neurobiol 1991; 17: 69–74
- 22 Roberts GW, Allsop D, Bruton CJ. The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 1990; 53: 373–378
- 23 Heyman A, Wilkinson WE, Stafford JA, et al. Alzheimer's disease: a study of epidemiological aspects. Ann Neurol 1984; 15: 335–341
- 24 Mortimer JA, French LR, Hutton JT, Schuman LM. Head trauma as a risk factor for Alzheimer's disease. Neurology 1985; 35: 264–267
- 25 Amaducci LA, Fratiglioni L, Rocca WA, et al. Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population. Neurology 1986; 36: 922–931
- 26 Graves AB, White E, Koepssell TD, et al. The association between head trauma and Alzheimer's disease. Am J Epidemiol 1990; 131: 491–501
- 27 vanDuijn CM, Tanja TA, Haaxma R, et al. Head trauma and the risk of Alzheimer's disease. Am J Epidemiol 1992; 135: 775–782
- 28 Mortimer JA, van Duijn CM, Chandra V, et al. Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. Int J Epidemiol 1991; 20 (suppl): S28–S35
- 29 Pittman J, Andrews H, Tatemichi T, et al. Diagnosis of dementia in a heterogenous population: a comparison of paradigm-based diagnosis and physician's diagnosis. Arch Neurol 1992; 49: 461–467
- 30 Stern Y. Andrews H. Pittman J. et al. Diagnosis of dementia in a heterogenous population: development of a neuropsychological paradigm and quantified correction for eduaction. Arch Neurol 1992; 49: 453–460
- 31 McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34: 939–944
- 32 Cutler SJ, Ederer F. Maximum utilization of life-table method in analyzing survival. J Chronic Dis 1958; 8: 699–712
- 33 Susser E, Susser M. Familial aggregation studies. A note on their epidemiological properties. Am J Epidemiology 1989; 129: 23–30
- 34 W J Dixson, ed. BMDP statistical software manual, vol 2. Los Angeles, CA: University of California Press, 1990
- 35 Fleiss JL. Statistical methods for rates and proportions. New York: John Wiley and Sons, 1981
- 36 Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull 1979; 86: 420–428
- 37 Sattin RW, Lambert-Huber DA, DeVito CA, et al. The incidence of fall injury events among the elderly in a defined population. Am J Epidemiol 1990; 131: 1028–1037
- 38 Nelson DE, Sattin RW, Langois JA, et al. Alcohol as a risk factor for fall injury events among elderly persons living in a community. J Am Geriatr Soc 1992; 40: 658–661
- 39 Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319: 1701–1707
- 40 Buchner DM, Larson EB. Falls and fractures in patients with Alzheimer-type dementia. JAMA 1987; 42: 412–417
- 41 Susser M. What is a cause and how do we know one? A grammer for pragmatic epidemiology. Am J Epidemiol 1991; 133: 635–648
- 42 Chandra V, Phillipose V, Bell PA, et al. Case-control study of late-onset probable Alzheimer's disease. Neurology 1987; 37: 1295–1300
- 43 Shalat SL, Seltzer B, Pidcock C, Baker EL. Risk factors for Alzheimer's disease: a case-control study. Neurology 1987; 37: 1630–1633
- 44 Chandra V, Kokmen E, Schoenberg BS. Beard CM. Head trauma with loss of consciousness as a risk factor for Alzheimer's disease. Neurology 1989; 39: 1576–1578
- 45 Katzman R, Aronson M, Fuld P, et al. Development of dementing illnesses in an 80 year old volunteer cohort. Ann Neurol 1989; 25: 317–324
- 46 Frendi-Strambi L, Smirne S, Garancini P, et al. Clinical and epidemiological aspects of Alzheimer's disease with presenile onset: a case-control study. Neuroepidemiology 1990; 9: 39–49
- 47 Broe GA, Henderson AS, Creasey H, et al. A case-control study of Alzheimer's disease in Australia. Neurology 1990; 40: 1698–1707
- 48 Williams DB, Annegers JF, Kokmen E, et al. Brain injury and neurologic sequelae: a cohort study of dementia, parkinsonism and amyotrophic lateral sclerosis. Neurology 1991; 41: 1554–1557
- 49 Kowall NW, McKee AC, Yanker BA, Beal MF. In vivo neurotoxicity of beta-amyloid [beta(1-40)] and the beta(25-35) fragment. Neurobiol Aging 1992; 13: 537–542
- 50 Cotman CW, Pike CJ, Copani A. Beta-amyloid neurotoxicity: a discussion of in vitro findings. Neurobiol Aging 1992; 13: 587–590
- 51 Koo EH, Soisodia SS, Cork LC, et al. Differential expression of amyloid precursor protein mRNAs in cases of Alzheimer's disease and in aged nonhuman primates. Neuron 1990; 2: 97–104
- 52 Gandy S, Greengard P. Amyloidogenesis in Alzheimer's disease: some possible therapeutic opportunities. TIPS 1992; 13: 108–113
- 53 Rocca W, Amaducci LA, Schoenberg BS. Epidemiology of Alzheimer's disease. In: D W Anderson, ed. Neuroepidemiology: a tribute to Bruce Schoenberg. Boca Raton, FL: CRC Press, 1991: 55–96
Citing Literature
