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

Abstract

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