Recall and recognition of verbal paired associates in early Alzheimer's disease

Lowndes, Georgina Johanna; Saling, Michael M.; Ames, David; Chiu, Edmond; Gonzalez, Linda; Savage, Greg

doi:10.1017/s1355617708080806

Cited by 25 publications

(19 citation statements)

References 84 publications

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“…The cognitive hallmark of AD is widely considered to be a deficit in episodic memory [17,45], and several memory tests have been proposed as suitable candidates for differentiating AD from depression. These include free delayed recall [28], rate of forgetting [55], recognition paradigms [e.g., 38] or the serial position curve [22]. However, none of these measures appear to combine sensitivity with specificity for AD when subjected to rigorous tests [20,23,32].…”

Section: Introductionmentioning

confidence: 99%

Alzheimer’s disease, but not ageing or depression, affects dual-tasking

et al. 2009

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Two experiments are reported that assess dual task performance in Alzheimer's disease (AD), in chronic depression and in healthy old age. Results suggest that dual task impairments are present in AD but are not shown in depression. This is true even when episodic memory performance is equated between the groups. These results, together with those of previous studies, point to dual task performance as an aid to diagnosis of AD relative to depression. This is of particular relevance when episodic memory tests cannot distinguish between the two conditions. The dual task paradigm appears to have considerable promise in assisting the early detection of the specific cognitive deficits associated with AD, and in monitoring their progression, both in the laboratory setting and in everyday tasks. Results also are of theoretical interest in pointing to a specific dual task coordination function in the healthy human cognitive system that allows for the coordination of two tasks performed simultaneously and which is damaged in AD but not in depression.

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Section: Introductionmentioning

confidence: 99%

Alzheimer’s disease, but not ageing or depression, affects dual-tasking

et al. 2009

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“…Based on literature references, some of the items were determined to be sensitive to change and therefore likely to improve the sensitivity of the ADAS-cog combination (30, 31). However, since there was no way to determine the weights from historic datasets, the weight for these items was an average of the weights selected for other items, scaled based on the range of the new item.…”

Section: Resultsmentioning

confidence: 99%

Methodological Aspects of the Phase Ii Study Aff006 Evaluating Amyloid-Beta -Targeting Vaccine Affitope® Ad02 in Early Alzheimer’s Disease – Prospective Use of Novel Composite Scales

et al. 2015

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BACKGROUND: Optimized scales and composite outcomes have been proposed as a way to more accurately measure Alzheimer’s disease related decline. AFFITOPE® AD02, is an amyloid-beta (Aβ)-targeting vaccine to elicit anti-Aβ antibodies. IMM-AD04, commonly known as Alum, originally designated as a control agent, appeared to have disease-modifying activity in a multicenter, parallel group phase II study in early AD patients. OBJECTIVES: To develop adapted outcomes for cognition, function and a composite scale with improved sensitivity to decline and treatment effects in early AD (mild plus prodromal AD) based on historical data and to assess these adapted outcomes in this phase II study. DESIGN: Data from public datasets was analyzed using a partial least squares model in order to identify an optimally weighted cognitive outcome, Adapted ADAS-cog, and an optimally weighted ADL outcome, Adapted ADCS-ADL which were prospectively defined as co-primary endpoints for the study and were also combined into a composite scale. Data from 162 patients in the placebo groups of ADCS studies and 156 mild patients in the ADNI I study were pooled for this analysis. The Adapted ADAS-cog scale considered 13 ADAS-cog items as well as several Neuropsychological test items and CogState items, the Adapted ADCS-ADL considered all ADCS-ADL items. After the pre-specified analyses were complete, additional adapted and composite scales were investigated in a post-hoc manner. Evaluation of the adapted and composite scales was performed on Phase II trial data for AFFITOPE® AD02 (AFF006, Clinical Trial Identifier: NCT01117818) and historic data in early AD. Least square means, standard deviations, and least squares mean to standard deviation ratios were compared among adapted and composite scales and traditional scales for the 5 treatment groups in the phase II study and overall for the historic data. Treatment effect sizes and p-values were also compared for the phase II study. RESULTS: Cognitive items that were selected for the adapted cognitive scale (aADAS-cog) and had the highest weights were Word Recall, Word Recognition, and Orientation. Delayed Word Recall and Digit Cancellation were among the items excluded due to lack of improved sensitivity to decline. Highly weighted ADL items included in the adapted functional scale (aADCS-ADL) were using the telephone, traveling, preparing a meal/snack, selecting clothing, shopping and using appliances. Excluded items were primarily basic ADLs such as eating, walking, toileting and bathing. Comparisons between traditional scales and primary outcome adapted scales show improved sensitivity to group differences with the adapted scales in the phase II trial. Most of the improvement in the sensitivity of the aADAS-cog and the aADCS-ADL is due to a larger treatment difference observed rather than the improved sensitivity to decline in the comparison groups. CONCLUSION: To our knowledge, this is the first study to prospectively use optimized scales as primary endpoints and to demonstrate the superior power of optimized scales and composites in early disease. Although it is possible that the treatment difference between randomized groups is due to a factor other than the treatment itself, for instance baseline imbalance, the improved power to detect these differences still argues in favor of the adapted scales. The issue of oversensitivity to detect treatment effects is controlled by selection of the alpha level for significance, and in our case will happen less than 5% of the time. Clinical relevance of the treatment difference should be assessed separately from statistical significance, and in this phase II study, is supported by significant or similar sizes of effect on function, behaviour and quality of life outcomes, which are important to patients and caregivers.

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“…The PAL task has been extensively studied in humans using a variety of modalities (verbal, visual, locations) (Egerhazi et al 2007;Lowndes et al 2008a;Lowndes et al 2008b). As used here, PAL involves the encoding and retrieval of object-location information.…”

Section: Discussionmentioning

confidence: 99%