Memory impairment, executive dysfunction, and intellectual decline in preclinical Alzheimer's disease

Department of Neurology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10467, USA.
Journal of the International Neuropsychological Society (Impact Factor: 2.96). 04/2008; 14(2):266-78. DOI: 10.1017/S1355617708080302
Source: PubMed


In the Baltimore Longitudinal Study of Aging (BLSA), we examined the temporal unfolding of declining performance on tests of episodic memory (Free Recall on the Free and Cued Selective Reminding Test), executive function (Category Fluency, Letter Fluency, and Trails), and Verbal Intelligence (Nelson, 1982; American Version of the Nelson Adult Reading Test [AMNART]) before the diagnosis of dementia in 92 subjects with incident Alzheimer's disease (AD) followed for up to 15 years before diagnosis. To examine the preclinical onset of cognitive decline, we aligned subjects at the time of initial AD diagnosis and examined the cognitive course preceding diagnosis. We found that declines in performance on tests of episodic memory accelerated 7 years before diagnosis. Declining performance on tests of executive function accelerated 2-3 years before diagnosis, and verbal intelligence declined in close proximity to diagnosis. This cognitive profile is compatible with pathologic data suggesting that structures which mediate memory are affected earlier than frontal structures during the preclinical onset of AD. It also supports the view that VIQ as estimated by the AMNART does not decline during the preclinical onset of AD.

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    • "Our findings further indicated decline in verbal fluency for both groups, which is also reported by a population-based study (Clark et al. 2009). Moreover, significant decline on fluency measures prior to AD dementia diagnosis is reported by multiple populationbased studies (Grober et al. 2008; Raoux et al. 2008; Laukka et al. 2012). Our established decline for nonconverters might be due to an underlying ageing process, which is reported for verbal fluency by other studies (Crossley et al. 1997; Auriacombe et al. 2001). "
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    ABSTRACT: We investigated the course of decline in multiple cognitive domains in non-demented subjects from a memory clinic setting, and compared pattern, onset and magnitude of decline between subjects who progressed to Alzheimer's disease (AD) dementia at follow-up and subjects who did not progress. In this retrospective cohort study 819 consecutive non-demented patients who visited the memory clinics in Maastricht or Amsterdam between 1987 and 2010 were followed until they became demented or for a maximum of 10 years (range 0.5-10 years). Differences in trajectories of episodic memory, executive functioning, verbal fluency, and information processing speed/attention between converters to AD dementia and subjects remaining non-demented were compared by means of random effects modelling. The cognitive performance of converters and non-converters could already be differentiated seven (episodic memory) to three (verbal fluency and executive functioning) years prior to dementia diagnosis. Converters declined in these three domains, while non-converters remained stable on episodic memory and executive functioning and showed modest decline in verbal fluency. There was no evidence of decline in information processing speed/attention in either group. Differences in cognitive performance between converters to AD dementia and subjects remaining non-demented could be established 7 years prior to diagnosis for episodic memory, with verbal fluency and executive functioning following several years later. Therefore, in addition to early episodic memory decline, decline in executive functions may also flag incident AD dementia. By contrast, change in information processing speed/attention seems less informative.
    Full-text · Article · Nov 2014 · Psychological Medicine
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    • "Episodic memory is involved in learning and retaining new pieces of information over a period of delay. Both crosssectional and longitudinal studies show that episodic memory is the earliest and most severely affected cognitive domain in AD [2] [3]. Although numerous studies have emphasized the importance of declines in learning with repeated trials (as reflected in a total learning score across immediate recall trials) and short and long delayed recall performance on tests of verbal episodic memory as early indicators of AD [4] [5] [6] [7] [8] [9], there is no consensus as to whether immediate or delayed recall is affected earlier within the domain of verbal episodic memory. "
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    ABSTRACT: Background The delineation of the relative temporal trajectories of specific cognitive measures associated with Alzheimer's disease (AD) is important for evaluating preclinical markers and monitoring disease progression. Methods We characterized the temporal trajectories of measures of verbal episodic memory, short-term visual memory, and mental status using data from 895 participants in the Baltimore Longitudinal Study of Aging. Results The California Verbal Learning Test (CVLT) immediate recall was the first measure to decline, followed by CVLT delayed recall. However, further along the disease progression scale, CVLT delayed recall and visual memory changed more rapidly than CVLT immediate recall. Conclusions Our findings reconcile reports of early changes in immediate recall with greater reliance on delayed recall performance in clinical settings. Moreover, the utility of cognitive markers in evaluating AD progression depends on the stage of cognitive decline, suggesting that optimal endpoints in therapeutic trials may vary across different stages of the disease process.
    Full-text · Article · Nov 2014 · Alzheimer's and Dementia
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    • "Taking into account that many patients with MCI are still employed, the observed improvement in TMT performance may have an influence on their ability to cope with demands of working life. Moreover, low scores in executive function were reported to be associated with shorter time to progression to AD (Blacker et al., 2007), and accelerated decline in executive function was observed within 2–3 years before the diagnosis of dementia (Grober et al., 2008). Whereas both patients and informants were equally likely to rate global change as favorable in the EGb 761-treated group, more patients than caregivers perceived changes under placebo intake as favorable. "
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    ABSTRACT: Objective The study was conducted to explore the effects of EGb 761® (Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany) on neuropsychiatric symptoms (NPS) and cognition in patients with mild cognitive impairment (MCI).Methods One hundred and sixty patients with MCI who scored at least 6 on the 12-item Neuropsychiatric Inventory (NPI) were enrolled in this double-blind, multi-center trial and randomized to receive 240 mg EGb 761 daily or placebo for a period of 24 weeks. Effects on NPS were assessed using the NPI, the state sub-score of the State-Trait Anxiety Inventory and the Geriatric Depression Scale. Further outcome measures were the Trail-Making Test (A/B) for cognition and global ratings of change. Statistical analyses followed the intention-to-treat principle.ResultsThe NPI composite score decreased by 7.0 ± 4.5 (mean, standard deviation) points in the EGb 761-treated group and by 5.5 ± 5.2 in the placebo group (p = 0.001). Improvement by at least 4 points was found in 78.8% of patients treated with EGb 761 and in 55.7% of those receiving placebo (p = 0.002). Superiority of EGb 761 over placebo (p < 0.05) was also found for the State-Trait Anxiety Inventory score, the informants' global impression of change, and both Trail-Making Test scores. There were statistical trends favoring EGb 761 in the Geriatric Depression Scale and the patients' global impression of change. Adverse events (all non-serious) were reported by 37 patients taking EGb 761 and 36 patients receiving placebo.ConclusionsEGb 761 improved NPS and cognitive performance in patients with MCI. The drug was safe and well tolerated. Copyright © 2014 John Wiley & Sons, Ltd.
    Full-text · Article · Oct 2014 · International Journal of Geriatric Psychiatry
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