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

ABSTRACT 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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    • "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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    • "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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    • "This was explored by controlling for normalized volume of relevant GM or WM structures in the case of significant DTI-CSF partial correlations (i.e., adding left hippocampus volume or left fornix volume to the significant left fornix WM integrityeCSF models). Finally, the functional relevance of significant DTIeCSF associations was explored through partial correlations between FA in that ROI and 2 UDS cognitive test scores of high relevance to preclinical AD states (Logical Memory Delayed and Digit Symbol) (Blacker et al., 2007; Dickerson et al., 2007), as well as a control measure of psychomotor speed (Trails A). To limit the number of comparisons, relationships between other more specific component diffusivity measures (DR/DA/MD) and these cognitive tests were only explored in the presence of significant FA-cognitive score relationships. "
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