Preclinical Alzheimer’s Disease
ABSTRACT & COMMENTARY
Source: Elias MF, et al. The preclinical phase of Alzheimer disease: A 22-year prospective study of the Framingham Cohort. Arch Neurol 2000;57:808-813.
Early detection of alzheimer’s disease (ad) is increasingly important because of advances being made with respect to prognostic methods and therapeutic interventions. Therefore, it is important to determine the earliest evidence of cognitive decline signaling the "preclinical phase" of AD and to identify specific neuropsychological tests that have clinical use in the prediction of this disorder. The "preclinical phase" is defined as a period of cognitive decline that preceded the onset of AD. In the present study, Elias and associates related the performance on tests of cognitive ability to the subsequent development of probable Alzheimer’s disease (pAD) and attempted to identify the pattern of earliest changes in cognitive functioning associated with a diagnosis of pAD.
Subjects were 1076 participants of the Framingham Study, aged 65-94 years, who were free of dementia and stroke at baseline. A screening neuropsychological battery was administered to all participants. They were followed prospectively for 22 years and examined at least every two years for the development of pAD. Neuropsychological testing included: logical memory-immediate recall, logical memory-retained, controlled word association, similarities, visual reproductions, paired associate learning, digit span forward, and digit span backward.
During follow-up, a panel of neuropsychologists and a neurologist reviewed all cases of suspected dementia. The panel reviewed neurological findings, neuropsychological findings, Framingham Study and hospital records, and results of brain imaging studies when available. One hundred nine subjects met the criteria for a diagnosis of pAD. The only demographic difference (sex, education, occupation, and age) between cases of pAD and non-cases was that subjects who developed pAD were older than subjects who remained free of pAD. Statistically significant associations between lower test scores and AD were observed for Logical Memory-Retained, Similarities, Paired Associate Learning, and the Learning and Immediate Recall composite score. No significant association between Controlled Oral Word Association scores and pAD outcome was observed for the younger cohort (65-74 years), but lower Controlled Oral Word Association scores were associated with higher risk of later diagnosis of pAD in the older cohort (75-94 years).
COMMENT BY CLAUDIA A. ORENGO, MD, PhD
Lower scores on measure of episodic and semantic memory processes, acquisition, and abstract reasoning are risk factors for the subsequent development of AD. Interestingly, Controlled Oral Word Association performance has been a predictor of pAD in previous studies; however, this was only true for the 75 to 94-year-old participants in this study and not the younger participants. It could be argued that AD with onset at a younger age is predicated by a different set of variables than AD with onset at an older age, and those preclinical decrements in semantic memory predict late-onset AD.
It is important to note that poor performance on measures of retention and abstract reasoning herald pAD at least 10 years before it is diagnosed. A limitation of this study is that due to the conservative criteria for diagnosing pAD, mild cases of pAD are not necessarily diagnosed. The patterns of tests related to the prediction of pAD in the present study apply only to moderate to severe AD. Conversely, the strength of this study is that it has a large community sample that was followed prospectively during a 22-year period and the number of pAD cases is large compared to previous studies.
In conclusion, lowered cognitive functioning is an indication of AD and scores on measures of new learning, retention, abstract reasoning, episodic memory, and semantic memory forecast a diagnosis of pAD.
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