Objective:
The UCLA/VA Family Study of Alzheimer Disease (AD) is one of the earliest prospective longitudinal family studies with state-of-the-art diagnosed AD probands, whose siblings and children received neurocognitive testing, psychiatric, medical and neurological evaluations on repeated occasions. These relatives are now reaching ages which place them at risk for the manifestation of AD. First-degree relatives of identified AD patients constitute an ideal population for longitudinal study since they are at increased risk with reduced genetic and, to some extent, environmental heterogeneity.
Despite major advances in the understanding of key elements in AD, etiology, and pathogenesis remain largely unknown. Specific genetic factors have been identified in a small number of families with early disease onset, accounting for less than 5% of AD patients. In addition, some risk factors have been established, as diverse as the gene APOE-e4, a history of head trauma, advancing age, and a positive family history of dementia.
This pilot study examines the following two questions:
1.) To what extent do neurocognitive changes observed during the first 10-year follow-up predict neurocognitive change during the second 10 years?
2.) Does the relationship observed in our first 10-year follow-up between age at onset of AD in the proband and cognitive change in first-degree relatives, persist during the next 10-year follow-up?
Materials and Methods:
Participants in this 20-year follow-up study are members of 89 families with probands diagnosed as “probable” or “definite” AD. For purposes of this pilot study, a convenient sub-sample was selected based on geographic proximity and availability. All subjects gave informed consent and participated in face-to-face meetings. They provided interim medical, social, occupational, and family histories, as well as medical records and gave blood samples for clinical laboratory and genetic tests. They also underwent a psychiatric screening and neurocognitive testing based on standardized instruments.
Results & Conclusion:
Twenty-seven children from 17 original probands were re-evaluated in 2002 and 2003. Thirteen of the 17 probands had autopsies (all confirmed the diagnosis of AD) while the remaining 4 did not, but did have clinical diagnoses of “probable AD”. Each proband was classified as familial, sporadic, or undetermined (n = 7, 6 and 4, respectively) based on presence of dementia in other family members.
The test-retest interval for the 27 relatives ranged from 10 to 22 years (M=19.2 years) between initial and most recent evaluations. Participants (41% men) range in age from 50 to 82 years (M=60.6, Median= 60) and all have at least a high school education. As stated above (Objective), currently data analyses focus on neurocognitive findings.
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