Trajectories of brain loss in aging and the development of cognitive impairment.
BACKGROUND
The use of volumetric MRI as a biomarker for assessing transitions to dementia presumes that more rapid brain loss marks the clinical transition from benign aging to mild cognitive impairment (MCI). The trajectory of this volume loss relative to the timing of the clinical transition to dementia has not been established.


METHODS
The authors annually evaluated 79 healthy elderly subjects for up to 15 consecutive years with standardized clinical examinations and volumetric brain MRI assessments of ventricular volume. During the study period, 37 subjects developed MCI. A mixed effects model with a change point modeled the pattern of brain volume loss in healthy aging compared with subjects diagnosed with MCI.


RESULTS
The brain loss trajectory of subjects developing MCI during follow-up differed from healthy aging in a two-phase process. First, the annual rate of expansion of ventricular volume decreased with age; however, the annual rates of expansion were greater in those who developed cognitive impairment during follow-up compared with those who did not. Further, subjects who developed MCI had an acceleration of ventricular volume expansion approximately 2.3 years prior to clinical diagnosis of MCI.


CONCLUSIONS
Ventricular expansion is faster in those developing mild cognitive impairment years prior to clinical symptoms, and eventually a more rapid expansion occurs approximately 24 months prior to the emergence of clinical symptoms. These differential rates of preclinical atrophy suggest that there are specific windows for optimal timing of introduction of dementia prevention therapies in the future.
Division of Biostatistics, Department of Public Health and Preventive Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Mail Code CB669 Portland, OR 97239, USA carlsoni@ohsu.edu
N E
NE
Carlson
M M
MM
Moore
A
A
Dame
D
D
Howieson
L C
LC
Silbert
J F
JF
Quinn
J A
JA
Kaye
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D001284:Atrophy / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D001921:Brain / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000639:trends; D008297:Male; D008875:Middle Aged