Send to

Choose Destination
See comment in PubMed Commons below
Neurology. 2008 Mar 11;70(11):828-33. Epub 2007 Nov 28.

Trajectories of brain loss in aging and the development of cognitive impairment.

Author information

  • 1Division 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



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.


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.


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.


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.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk