Role of familial factors in late-onset Alzheimer disease as afunction of age
Z. Wu
Bok Engelsk 1998
| Utgitt | 1998
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| Omfang | Side 190- 197
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| Opplysninger | Whereas early-onset Alzheimer disease (AD; usually onset at age < 50years) has been defined with genetic mutation on chromosomes 1, 14,and 21, the degree of familial contribution to late-onset AD isunclear. Further, it is uncertain if subgroups of late-onset ADexist. To examine the influence of familial factors as a function ofage in late-onset AD we investigated lifetime risks and age-specifichazard rates of AD-like illness among late-onset AD probands' andcontrols' first-degree relatives, using questionnaires and medicalrecords. As part of a longitudinal study on aging and AD, we studied78 AD probands with age of onset greater than or equal to 50 years(28 ''definite'' and 50 ''probable'' AD according to NINCDS/ADRDAcriteria) and 101 healthy old controls seen since 1981. Both probandsand controls were screened rigorously with medical tests and brainimaging and seen regularly until autopsy. Multiple informants andmedical records were used for first-degree relatives. Among first-degree relatives, 49 secondary cases of AD-like illness were foundfor the AD probands' relatives (391 relatives 40 years old or older)compared with 20 cases among controls' relatives (456 relatives 40years old or older). Relatives of AD probands had a significantlyincreased lifetime risk of AD-like illness of 52.8 +/- 11.4% by age94 years compared with a lifetime risk in relatives of controls of22.1 +/- 5.8% by age 90 years. Age-specific hazard rates in relativesof AD probands increased until the 75-79-year age interval and thendecreased; in contrast the age-specific hazard rates increased inrelatives of controls after the 80-84-year age interval. To determineif a dividing line exist among late-onset AD, several cutoff ageswere used in our study to compare cumulative risk curves of AD-likeillness between relatives of late-onset probands and relatives oflate-late-onset probands. Differences in the pattern of cumulativeincidence of AD in relatives showed that 67-71 years is the range fora dividing line between late- and late-late-onset AD. Age specifichazard rates of AD in relatives supported a difference between late-and late-late-onset. Whereas these rates increased until the 75-79-year age interval and then decreased in late-onset AD, the ratesbegan increasing after the 65-69-year age interval and through theoldest age interval in both late-late-onset AD and control groups,Our results support the concept that familial factors exist in late-onset AD and that different familial factors may exist in late-onsetAD subgroups.
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| Emner |
