Dual-retrieval models and neurocognitive impairment.

Advances in dual-retrieval models of recall make it possible to use clinical data to test theoretical hypotheses about mild cognitive impairment (MCI) and Alzheimer's dementia (AD), the most common forms of neurocognitive impairment. Hypotheses about the nature of the episodic memory declines in these diseases, about decline versus sparing of specific processes, and about which individuals will become impaired over time can all be rigorously tested. Basic theoretical principles, such as whether recollection and reconstruction are distinct retrieval processes, can also be evaluated. In 3 studies, measurements of recollective retrieval, reconstructive retrieval, and familiarity judgment were extracted from standard clinical instruments, for healthy subjects and for subjects with MCI and AD diagnoses. Differences in reconstructive retrieval consistently distinguished MCI and AD, in nationally representative subject samples as well as in highly educated samples, and recollective retrieval also distinguished them in highly educated samples. Dual-retrieval processes were accurate predictors of future conversion to MCI and AD over periods of 1.5-6 years and were better predictors than the best genetic marker of these conditions (the ε4 allele of the APOE genotype). The standard recollection-deficit account of memory declines in MCI and AD was not supported, but the data were consistent with an alternative account that stresses the increasing importance of reconstruction deficits as older adults convert to these diseases.

The apolipoprotein E genotype predicts longitudinal transitions to mild cognitive impairment but not to Alzheimer's dementia: findings from a nationally representative study.

OBJECTIVE: The ε4 allele of the apolipoprotein E (APOE) genotype is the most widely accepted genetic risk factor for Alzheimer's dementia (AD), but findings on whether it is a risk factor for the AD prodrome, mild cognitive impairment (MCI), have been inconsistent. In a prospective longitudinal design, we investigated (a) whether transitions to MCI and other forms of neurocognitive impairment without dementia (CIND) are more frequent among normal ε4 carriers than among noncarriers and (b) whether subsequent transitions to AD from MCI and from other forms of CIND are more frequent among ε4 carriers than among noncarriers. METHOD: The frequency of the ε4 allele was studied in older adults (mean age > 70), who had participated in two or more waves of neuropsychological testing and diagnosis in the Aging, Demographics, and Memory Study (ADAMS) of the United States Department of Health and Human Services, National Institutes of Health, National Institute on Aging's Health and Retirement Study, conducted by the University of Michigan. The association between ε4 and longitudinal transitions to specific types of CIND and dementia can be determined with this data set. RESULTS: Epsilon 4 increased the rate of progression from normal functioning to MCI (58% of new diagnoses were carriers) but not to other forms of CIND. The rate of progression to AD from MCI or from other forms of CIND was not increased by ε4. CONCLUSIONS: The results support the hypothesis that ε4 is a risk factor for transitions from normal functioning to MCI but not for subsequent transitions to AD. In the ADAMS sample, the reason ε4 is elevated in AD individuals is because it is already elevated in MCI individuals, who are the primary source of new AD diagnoses.