Cortical signatures of cognition and their relationship to Alzheimer's disease.
Recent changes in diagnostic criteria for Alzheimer's disease (AD) state that biomarkers can enhance certainty in a diagnosis of AD. In the present study, we combined cognitive function and brain morphology, a potential imaging biomarker, to predict conversion from mild cognitive impairment to AD. We identified four biomarkers, or cortical signatures of cognition (CSC), from regressions of cortical thickness on neuropsychological factors representing memory, executive function/processing speed, language, and visuospatial function among participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Neuropsychological factor scores were created from a previously validated multidimensional factor structure of the neuropsychological battery in ADNI. Mean thickness of each CSC at the baseline study visit was used to evaluate risk of conversion to clinical AD among participants with mild cognitive impairment (MCI) and rate of decline on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score. Of 307 MCI participants, 119 converted to AD. For all domain-specific CSC, a one standard deviation thinner cortical thickness was associated with an approximately 50% higher hazard of conversion and an increase of approximately 0.30 points annually on the CDR-SB. In combined models with a domain-specific CSC and neuropsychological factor score, both CSC and factor scores predicted conversion to AD and increasing clinical severity. The present study indicated that factor scores and CSCs for memory and language both significantly predicted risk of conversion to AD and accelerated deterioration in dementia severity. We conclude that predictive models are best when they utilize both neuropsychological measures and imaging biomarkers.
Institute for Aging Research, Harvard Medical School, Hebrew SeniorLife, 1200 Centre Street, Rm. 634, Boston, MA, USA. aldengross@hsl.harvard.edu
Alden L
AL
Gross
Jennifer J
JJ
Manly
Judy
J
Pa
Julene K
JK
Johnson
Lovingly Quitania
LQ
Park
Meghan B
MB
Mitchell
Rebecca J
RJ
Melrose
Sharon K
SK
Inouye
Donald G
DG
McLaren
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis*; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000150:complications / Q000175:diagnosis*; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011594:Psychometrics / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index