Clinical Prediction of Alzheimer Disease Dementia Across the Spectrum of Mild Cognitive Impairment

Harvard University, Cambridge, Massachusetts, United States
Archives of general psychiatry (Impact Factor: 14.48). 12/2007; 64(12):1443-50. DOI: 10.1001/archpsyc.64.12.1443
Source: PubMed


To determine whether clinical assessment methods that grade the severity of impairments within the spectrum of mild cognitive impairment (MCI) can predict clinical course, particularly among very mildly impaired individuals who do not meet formal MCI criteria as implemented in clinical trials.
Community volunteers.
From a longitudinal study of normal (Clinical Dementia Rating [CDR] = 0; n = 77) and mildly impaired (CDR = 0.5; n = 167) participants with 5 or more annual clinical assessments, baseline level of cognitive impairment in daily life was graded using CDR sum of boxes (CDR-SB) and level of cognitive performance impairment was graded using neuropsychological test scores.
Five-year outcome measures included (1) probable Alzheimer disease (AD) diagnosis and (2) clinical "decline" (CDR-SB increase > or = 1.0). Logistic regression models were used to assess the ability of baseline measures to predict outcomes in the full sample and separately in the subjects who did not meet formal MCI criteria as implemented in a multicenter clinical trial (n = 125; "very mild cognitive impairment" [vMCI]).
The presence of both higher CDR-SB and lower verbal memory and executive function at baseline predicted greater likelihood of probable AD and decline. Five-year rates of probable AD and decline in vMCI (20%, AD; 49%, decline) were intermediate between normal participants (0%, AD; 28%, decline) and participants with MCI (41%, AD; 62%, decline). Within vMCI, likelihood of probable AD was predicted by higher CDR-SB and lower executive function.
Even in very mildly impaired individuals who do not meet strict MCI criteria as implemented in clinical trials, the degree of cognitive impairment in daily life and performance on neuropsychological testing predict likelihood of an AD diagnosis within 5 years. The clinical determination of relative severity of impairment along the spectrum of MCI may be valuable for trials of putative disease-modifying compounds, particularly as target populations are broadened to include less impaired individuals.

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Available from: Bradford Dickerson, Dec 13, 2013
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    • "However, even if subjects identified as MCI (and in particular as amnestic MCI (aMCI) patients) on the basis of these criteria had an increased risk of progressing to dementia, most remained stable or even reverted from MCI to a 'normal' state. Furthermore, estimates of the annual conversion rate to dementia were very variable, ranging from less than 4%234to 20–30%5678. Therefore, several neuropsychological investigations tried to single out the best methods of identifying MCI patients who have a higher risk of converting to AD. "
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    ABSTRACT: Taking into the account both the severity and the consistency of performances obtained on memory test by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimer's disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles performances obtained at baseline in verbal (RAVLT) and visual episodic memory (Rey-Osterrieth Figure-delayed recall) and giving a score ranging from 1 (worst result) to 3 (best result) to results falling within each tertile. The EMS was computed for each patient by summing the tertile score obtained on each memory task, so that the total score ranged from 4 (worst performance) to 12 (best performance). The aMCI sample consisted of 198 subjects who completed the two-year follow-up, at the end of which 55 subjects had converted to dementia. The mean EMS score obtained by aMCI converters was significantly lower than that of aMCI-stable patients. In detecting conversion to dementia, the comparison between EMS and individual memory scores obtained at baseline was made by computing ROC curves, and estimating the respective area under the curve (AUC). The EMS had a larger AUC than the individual memory scores. At baseline aMCI converters performed worse than non-converters not only on memory tasks, but also on executive functions tasks. However, in a multiple variables logistic regression analysis in which all scores showing statistically significant differences between aMCI-converters and aMCI-stable were entered, the EMS was the only reliable predictor of progression from aMCI to dementia.
    Full-text · Article · Dec 2015 · Journal of Alzheimer's disease: JAD
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    • "The Clinical Dementia Rating (CDR) scale (Morris, 1993) is widely used in Alzheimer's disease clinical assessment and research trials to grade cognitive impairment and level of daily functioning. Research in Alzheimer's disease has shown that the sole use of performance-based measures, such as those typically used in stroke aphasiology (e.g., Boston Diagnostic Aphasia Examination (BDAE)) (Goodglass, Kaplan, & Barresi, 2000), fails to adequately capture information about symptom severity in daily life, while ratings of symptom severity based on the clinician's judgement may provide complementary information and help in the scoring of disease severity (Dickerson, Sperling, Hyman, Albert, & Blacker, 2007). In PPA clinical care and research programs as well, the use of a structured, semiquantitative instrument that allows the clinician to rate the relative severity of impairment in each language domain based on language assessment and patient and partner interview may provide a more complete clinical picture, rather than solely using information from test performance. "
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    Full-text · Article · Aug 2014 · Aphasiology
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    • "There are currently several means for predicting the progression of MCI, such as structural magnetic resonance imaging (MRI),13,14 functional imaging techniques ([18]F- fluorodeoxyglucose positron emission tomography),15 analysis of the biomarkers in cerebrospinal fluid,16 and the use of molecular imaging.17 "
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    ABSTRACT: A great amount of research has been developed around the early cognitive impairments that best predict the onset of Alzheimer’s disease (AD). Given that mild cognitive impairment (MCI) is no longer considered to be an intermediate state between normal aging and AD, new paths have been traced to acquire further knowledge about this condition and its subtypes, and to determine which of them have a higher risk of conversion to AD. It is now known that other deficits besides episodic and semantic memory impairments may be present in the early stages of AD, such as visuospatial and executive function deficits. Furthermore, recent investigations have proven that the hippocampus and the medial temporal lobe struc- tures are not only involved in memory functioning, but also in visual processes. These early changes in memory, visual, and executive processes may also be detected with the study of eye movement patterns in pathological conditions like MCI and AD. In the present review, we attempt to explore the existing literature concerning these patterns of oculomotor changes and how these changes are related to the early signs of AD. In particular, we argue that deficits in visual short-term memory, specifically in iconic memory, attention processes, and inhibitory control, may be found through the analysis of eye movement patterns, and we discuss how they might help to predict the progression from MCI to AD. We add that the study of eye movement patterns in these conditions, in combination with neuroimaging techniques and appropriate neuropsychological tasks based on rigorous concepts derived from cognitive psychology, may highlight the early presence of cognitive impairments in the course of the disease.
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