To determine the size of the impairment across different cognitive domains in preclinical Alzheimer's disease (AD), a meta-analysis based on 47 studies involving 9,097 controls and 1,207 preclinical AD cases was conducted. There were marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; somewhat smaller deficits in verbal ability, visuospatial skill, and attention; and no preclinical impairment in primary memory. Younger age (Ͻ 75 years) and shorter follow-up intervals (Ͻ 3 years) were associated with larger effect sizes for both global cognitive ability and episodic memory. For global cognitive ability, studies that used population-based sampling yielded larger effect sizes; for episodic memory, larger differences were seen in studies that preidentified groups in terms of baseline cognitive impairment. Within episodic memory, delayed testing and recall-based assessment resulted in the largest effect sizes. The authors conclude that deficits in multiple cognitive domains are characteristic of AD several years before clinical diagnosis. The generalized nature of the deficit is consistent with recent observations that multiple brain structures and functions are affected long before the AD diagnosis.

Cognitive studies show that both younger and older adults can increase their memory performance after training in using a visuospatial mnemonic, although age-related memory deficits tend to be magnified rather than reduced after training. Little is known about the changes in functional brain activity that accompany training-induced memory enhancement, and whether age-related activity changes are associated with the size of training-related gains. Here, we demonstrate that younger adults show increased activity during memory encoding in occipito-parietal and frontal brain regions after learning the mnemonic. Older adults did not show increased frontal activity, and only those elderly persons who benefited from the mnemonic showed increased occipitoparietal activity. These findings suggest that age-related differences in cognitive reserve capacity may reflect both a frontal processing deficiency and a posterior production deficiency.T he existence of age-related deficits in episodic memory functioning are well documented (1). Given the impact of such deficits, much research has been directed at examining possible means of enhancing memory performance in older adults by various forms of cognitive support (2). One approach that has received considerable attention involves estimation of latent cognitive potential, or cognitive reserve capacity, in older age (3). In one variant of this approach, younger and older participants are given training in using a classical mnemonic, the method of loci (4), to memorize and retrieve words. This method involves learning to visualize a series of mental landmarks (e.g., places along one's route to work). After acquisition of the landmarks, the to-be-remembered information is linked to the various loci at the time of encoding. At test, the landmarks are mentally revisited in serial order, and the information associated with each locus is retrieved.Serial recall is substantially enhanced by the loci mnemonic for both younger and older adults (5, 6), demonstrating cognitive reserve capacity in aging (i.e., cognitive reserve capacity is defined as the ability to enhance one's memory performance after learning a mnemonic). However, the most striking aspect of previous findings is that age differences in memory performance are magnified rather than reduced after training (7). This pattern of results suggests an age-related decrease in cognitive reserve capacity. Little is known about the basis for this phenomenon. Baltes and Kliegl (7) hypothesized that older adults may have difficulty in forming novel relations between the landmarks and the to-be-remembered information (i.e., a difficulty in using rather than acquiring the mnemonic), and they proposed neurobiological constraints as a determinant of this deficit. However, no direct evidence for this account has been provided. Here, we present the results from an age-comparative positron emission tomography (PET) study of the neural underpinnings of acquisition and use of the loci method. MethodsTasks and Procedure. The whole experiment,...

The literature on cognitive markers in preclinical AD is reviewed. The findings demonstrate that impairment in multiple cognitive domains is typically observed several years before clinical diagnosis. Measures of executive functioning, episodic memory and perceptual speed appear to be most effective at identifying at-risk individuals. The fact that these cognitive domains are most implicated in normal cognitive aging suggests that the cognitive deficit observed preclinically is not qualitatively different from that observed in normal aging. The degree of cognitive impairment prior to the diagnosis of Alzheimer's disease (AD) appears to generalize relatively well across major study characteristics, including sample ascertainment procedures, age and cognitive status of participants, as well as time to diagnosis of dementia. In episodic memory, there is evidence that the size of the preclinical deficit increases with increasing cognitive demands. The global cognitive impairment observed is highly consistent with observations that multiple brain structures and functions are affected long before the diagnosis of AD. However, there is substantial overlap in the distribution of cognitive scores between those who will and those who will not be diagnosed with AD, hence limiting the clinical utility of cognitive markers for early identification of cases. Future research should consider combining cognitive indicators with other types of markers (i.e. social, somatic, genetic, brain-based) in order to increase prediction accuracy.

In this article, the authors compare 3 generic models of the cognitive processes in a categorization task. The cue abstraction model implies abstraction in training of explicit cue-criterion relations that are mentally integrated to form a judgment, the lexicographic heuristic uses only the most valid cue, and the exemplar-based model relies on retrieval of exemplars. The results from 2 experiments showed that, in lieu of the lexicographic heuristic, most participants spontaneously integrate cues. In contrast to single-system views, exemplar memory appeared to dominate when the feedback was poor, but when the feedback was rich enough to allow the participants to discern the task structure, it was exploited for abstraction of explicit cue-criterion relations.