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O4–04–07: Treatment of mild cognitive impairment with vitamin E and donepezil: Correlation between rates of change on MRI and cognitive/behavioral measures
Author(s) -
Jack Clifford R.,
Petersen Ronald C.,
Grundman Michael,
Ward Chadwick,
Jin Shelia,
Gamst Anthony,
Sencakova Drahomira,
Thal Leon J.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.324
Subject(s) - magnetic resonance imaging , medicine , donepezil , atrophy , hippocampus , cognition , entorhinal cortex , dementia , psychology , audiology , physical therapy , radiology , psychiatry , disease
Background: The vitamin E and donepezil study for the treatment of mild cognitive impairment (MCI) was conducted at 69 centers with 769 participating subjects. Clinical results of this study have been previously reported (NEJM 2005; 352(23):2379-88). Twenty-four of the recruiting sites voluntarily participated in a magnetic resonance imaging (MRI) arm of the study. Objective(s): We report correlations between rates of atrophy from serial MRI and rates of change in widely used cognitive/behavioral measures MMSE, CDR, and ADAS in those subjects participating in the MRI arm of the study. Methods: 194 subjects participated in the MRI arm of the study and 137 completed both a baseline and followup scan. The followup MRI scan for each subject could have been either at the end of the study (36 months) or at an interim time point associated with clinical conversion from MCI to AD. In each subject percent change from baseline to followup was measured for four different brain volumes; hippocampus, entorhinal cortex (ERC), whole brain, and ventricle. The percent change from baseline to followup was also calculated for the MMSE, CDR, and ADAS. Correlations were performed between each MRI measure and each of the three behavioral/cognitive measures. Results: Correlations between rates of change in MMSE, CDR, ADAS and concurrent MRI rates of atrophy were significant for all four MRI rate measures (p 0.000 to 0.006). Correlations between baseline hippocampal volume and baseline MMSE, CDR, and ADAS were significant (all p 0.005). Conversely, with one exception, all correlations between the baseline behavioral/cognitive measures, and the baseline ECR, ventricular, and total brain volume were non-significant. Conclusion: The uniformly significant correlation between rates of change on MRI and concurrent change on MMSE, CDR, and ADAS validates serial MRI as a potential surrogate measure of disease progression in MCI subjects in a multi site therapeutic trial setting. In contrast, only the head-size-adjusted baseline hippocampal volumes correlated well with baseline cognitive test performance. This disassociation implies that only hippocampal volume satisfactorily maps onto cognitive status at a specific point in time, whereas any of the four MRI rate measures assessed satisfactorily map onto concurrent change in cognitive test performance.