J Neurol Neurosurg Psychiatry 84:71-78 doi:10.1136/jnnp-2012-303579
  • Cognition

Dynamics of brain structure and cognitive function in the Alzheimer's disease neuroimaging initiative

  1. for the Alzheimer's Disease Neuroimaging Initiative
  1. 1Biodiagnostics Atlantic, National Research Council Canada, Halifax, Canada
  2. 2Division of Geriatric Medicine, Dalhousie University, Halifax, Canada
  3. 3Department of Mathematics and Statistics, Dalhousie University, Halifax, Canada
  4. 4Department of Radiology, Tianjin Medical University, Tianjin, China
  5. 5Centre for Health Care of the Elderly, QEII Health Sciences Centre, Halifax, Canada
  1. Correspondence to Professor Kenneth Rockwood, Suite 1421, 5955 Veterans’ Memorial Lane, Halifax, Nova Scotia, Halifax B3H 2E1, Canada; Kenneth.Rockwood{at}
  • Received 7 July 2012
  • Revised 29 August 2012
  • Accepted 20 September 2012
  • Published Online First 2 November 2012


Background On average, cognition declines as people age, but improvement can also occur.

Objective To evaluate the dynamics of age-related changes in brain structure and cognitive function in patients with mild Alzheimer's disease (AD) and mild cognitive impairment (MCI) and in healthy control (HC) older adults.

Methods High-resolution 3-Tesla MRI and clinical data were obtained from the Alzheimer's Disease Neuroimaging Initiative in 187 subjects (a cohort aged 55–91 years; AD=43, MCI=84, HC=60). At 24 months, 151 people had clinical and 128 had MRI follow-up. Brain structure was assessed using the Medial Temporal Atrophy Scale (MTAS) and the Brain Atrophy and Lesion Index (BALI). Cognition was assessed using the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Responsiveness was tested. Changes were analysed using a multistate dynamic model, adjusted for age, gender, ApoE4 genotype and vascular risk factors.

Results Over 2 years, decline in brain structure and cognition predominated, each showing detectable effect sizes (Cohen's d=0.33 for MTAS, 0.32 for BALI, 0.41 for MMSE, 0.38 for ADAS-cog; standard response mean=0.71, 0.69, 0.50 and 0.47, respectively). Structural improvement was observed (10.2% in BALI and 0.8% in MTAS), as was cognitive improvement (23.2% MMSE, 27.2% ADAS-cog). Most people (66.7%) whose BALI score improved also improved in either the MMSE or ADAS-cog. No patient with MCI whose MTAS or BALI improved converted to AD.

Conclusions Despite average decline in brain structure, improvement was observed and related to cognition and MCI–AD conversion. Ageing-related brain changes reflect a dynamic process.

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