Bartnik Olson, B.L., Holshouser, B.A., Britt, W., Mueller, C., Baqai, W., Patra, S., Petersen, F., Kirsch, W.M. (2008) Longitudinal metabolic and cognitive changes in mild cognitive impairment patients. Alzheimer Disease & Associated Disorders 22(3): 269-277. ( 0/2008 )
Advancements in clinical therapies have identified the need for biomarkers of early Alzheimer’s disease (AD) that distinguish the earliest stages of pathology and target those patients that are likely to gain the most benefit. The aim of this study was to characterize the longitudinal metabolic changes measured by 1H magnetic resonance spectroscopy (MRS) in correlation to neuropsychological indices of episodic memory, attention and mental processing speed, language facility, and executive function in subjects with mild cognitive impairment (MCI). Quantitative 1HMRS of the posterior cingulate gyrus was performed and repeated at 11.56 ± 4.3 months. N-acetyl aspartate (NAA), total choline (Cho), total creatine (Cr), myo-inositol (mI) and glutamate/glutamine (Glx) metabolite levels were measured, corrected for CSF dilution, and ratios calculated in MCI and cognitively normal subjects. In the first study MCI subjects showed lower NAA levels, NAA/Cho and NAA/mI ratios and increased Cho/Cr and mI/Cr compared to controls. In the follow-up study, 36% of the MCI subjects (atypical MCI, atMCI) showed interval increases in NAA, Cr and Glx levels compared to 64% of MCI subjects (typical MCI, tMCI) that showed an interval decrease in NAA, Cr, and Glx. Both MCI subgroups had higher Clinical Dementia rating (CDR) scores and lower scores on episodic memory, phonemic and semantic word fluency tasks, compared to controls. The annualized rate of change in metabolic and cognitive status did not differ between normal aging and MCI subjects. atMCI subjects showed significant negative correlations between metabolite levels and executive function task scores, with NAA/mI showing a significant positive correlation with phonemic and semantic word fluency. There were no significant correlations between metabolite levels and cognitive performance in atMCI subjects however; NAA/mI and mI/Cr were negatively correlated with executive function tasks. These results indicate two distinct evolving metabolite profiles that correlate with changes in executive function and can be used to differentiate MCI from normal aging.