Sari Jones

Cognitive impairment in preclinical Alzheimer's disease: a meta-analysis.

To determine the size of the impairment across different cognitive domains in preclinical Alzheimers 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 (< 75 years) and shorter follow-up intervals (< 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.

Multiple cognitive deficits during the transition to Alzheimer's disease

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 Alzheimers 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.

Neural correlates of training-related memory improvement in adulthood and aging

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 occipito-parietal activity. These findings suggest that age-related differences in cognitive reserve capacity may reflect both a frontal processing deficiency and a posterior production deficiency.

Cognitive and neural plasticity in aging: General and task-specific limitations

There is evidence for cognitive as well as neural plasticity across the adult life span, although aging is associated with certain constraints on plasticity. In the current paper, we argue that the age-related reduction in cognitive plasticity may be due to (a) deficits in general processing resources, and (b) failure to engage in task-relevant cognitive operations. Memory-training research suggests that age-related processing deficits (e.g., executive functions, speed) hinder older adults from utilizing mnemonic techniques as efficiently as the young, and that this age difference is reflected by diminished frontal activity during mnemonic use. Additional constraints on memory plasticity in old age are related to difficulties that are specific to the task, such as creating visual images, as well as in binding together the information to be remembered. These deficiencies are paralleled by reduced activity in occipito-parietal and medial-temporal regions, respectively. Future attempts to optimize intervention-related gains in old age should consider targeting both general processing and task-specific origins of age-associated reductions in cognitive plasticity.

Cognitive deficits in preclinical Alzheimer's disease

We review the literature on cognitive functioning during the transition from normal aging to clinical Alzheimers disease (AD). There is ample empirical evidence that deficits across multiple cognitive domains are apparent years to decades before the AD diagnosis, with impairments in episodic memory representing a common cognitive manifestation of the preclinical phase of the disease. Interestingly, the magnitude of the preclinical cognitive deficits appears to be relatively stable until a few years before clinical diagnosis. The behavioural deficits associated with preclinical AD are consistent with the neural changes that appear many years before eventual diagnosis. In addition to increasing our theoretical understanding of AD development, research on cognition in preclinical AD contributes to the identification of persons at risk of developing AD for purposes of intervention.

Patterns of prospective and retrospective memory impairment in preclinical Alzheimer's disease

Forty-six preclinical Alzheimers disease (AD) participants and 188 nondemented control persons from the Kungsholmen Project (L. Bäckman et al., 2004) were compared on prospective memory (ProM) and retrospective memory (RetM) tasks 3 years before dementia diagnosis. The preclinical AD participants showed deficits in both ProM and RetM. Most interestingly, logistic regression analyses revealed that ProM made an independent contribution to the prediction of AD over and above that of RetM. This finding suggests that ProM and RetM tap partly different cognitive operations. Furthermore, within the ProM task, both the retrospective and prospective components were similarly impaired in preclinical AD. Within RetM, the preclinical AD participants were impaired on indices of encoding, storage (forgetting), and retrieval of information. Hence, the findings indicate a rather global episodic memory impairment in preclinical AD that cuts across type of memory assessed (ProM and RetM) as well as across different components of both the ProM and RetM tasks.

Similar patterns of cognitive deficits in the preclinical phases of vascular dementia and Alzheimer's disease

We investigated whether (1) cognitive deficits are present among persons who will be diagnosed with vascular dementia (VaD) 3 years later, and (2) the pattern of such deficits is similar to that observed in preclinical Alzheimers disease (AD). The VaD diagnosis was a diagnosis of post-stroke dementia. Population-based samples of 15 incident VaD cases, 43 incident AD cases, and 149 normal controls were compared on tests of episodic and short-term memory, verbal fluency, and visuospatial skill. Both dementia groups showed preclinical impairment relative controls on tasks assessing episodic memory 3 years before diagnosis, and there were no differences between these groups on any cognitive measure. The existence of a preclinical phase in the present VaD cases suggests that circulatory disturbance may affect cognitive performance before the occurrence of stroke that leads to clinical VaD. These results extend previous findings of similar patterns of cognitive deficits in the early clinical phases of AD and VaD to the preclinical phases of these diseases.

Cue abstraction and exemplar memory in categorization

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.

Differential Verbal Fluency Deficits in the Preclinical Stages of Alzheimer's Disease and Vascular Dementia

We examined patterns of early and late word generation in category and letter fluency among persons in the preclinical stages of Alzheimers disease (AD) and vascular dementia (VaD). The sample consisted of 20 preclinical VaD persons, 66 preclinical AD persons, and 267 control persons, sampled from the community. Persons in the preclinical phase of AD and VaD were similarly impaired in letter fluency, although the preclinical VaD group outperformed their AD counterparts in category fluency. This pattern of results is consistent with the notion that category fluency is relatively more dependent on the medial-temporal lobe, whereas letter fluency relies more on frontal regions. The patterns of fluency impairment in preclinical AD and VaD generalized across early and late word retrieval.

Cognitive Functioning in Preclinical Vascular Dementia A 6-Year Follow-Up

Background and Purpose— Recent studies have shown that cognitive deficits are present during the years preceding a diagnosis of vascular dementia (VaD). The aims of this study were to (1) extend previous research by examining whether cognitive deficits are already present 6 years before diagnosis, and (2) examine the strength of the association between cognitive performance and a future VaD diagnosis after controlling for previous vascular disorders. Methods— Subjects from a population-based study of very old persons (≥75) were examined with a test of global cognitive functioning (the Mini-Mental State Examination [MMSE]) at 3 occasions over a 6-year period. The study sample was nondemented the first 2 measurement times. On the last occasion, 22 individuals were diagnosed with VaD, and 450 persons remained nondemented. Results— The preclinical VaD group showed no MMSE deficits 6 years before diagnosis (P >0.10) compared with the controls. However, 3 years before diagnosis, poor cognitive performance was significantly associated with forthcoming VaD after controlling for demographic factors and prior vascular disorders (odds ratio, 2.55; 95% CI, 1.67 to 3.89). Conclusions— This study extends previous findings on preclinical cognitive deficits in VaD and suggests that cognitive measures can be useful in the process of recognizing individuals at risk for developing VaD to initiate early treatment.