Longitudinal Metabolic and Cognitive Changes in Mild Cognitive Impairment Patients

Abstract

Advancements in clinical therapies have identified the need for biomarkers of early Alzheimer disease that distinguish the earliest stages of pathology and target those patients who 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 in correlation to neuropsychologic indices of episodic memory, attention and mental processing speed, language facility, and executive function in subjects with mild cognitive impairment (MCI). Quantitative 1H magnetic resonance spectroscopy 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 cerebrospinal fluid 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 with controls. In the follow-up study, 36% of the MCI subjects [atypical MCI (atMCI)] showed interval increases in NAA, Cr, and Glx levels compared with 64% of MCI subjects (typical MCI) who showed an interval decrease in NAA, Cr, and Glx. Both MCI subgroups had higher Clinical Dementia Rating scores and lower scores on episodic memory, phonemic, and semantic word fluency tasks, compared with 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 tMCI subjects; however, NAA/mI and mI/Cr were negatively correlated with executive function tasks. These results indicate 2 distinct evolving metabolite profiles that correlate with changes in executive function and can be used to differentiate MCI from normal aging.

Advances in High-Field Magnetic Resonance Spectroscopy in Alzheimer’s Disease

“…NAA or NAA/Cr , especially those of the hippocampus, often correlate with memory test scores [83, 92, 97, 98] and so can be related to memory function and to predict AD with relatively high accuracy [91, 92, 98]. They also showed some localization effects, including two distinct metabolite profiles: whereas most subjects with MCI displayed a decrease in NAA , Cho , Cr , and Glx at the one-year follow-up, 36% of subjects showed an increase in NAA , which was associated with an improvement of executive function [82], suggesting a neurocompensatory response early in the course of AD. A study by Schott et al (2010), which involved six MRS evaluations over 24 months and compared clinically confirmed AD with healthy controls, reported that the baseline NAA/mI in the posterior cingulate gyrus distinguished AD from HC, with approximately 80% sensitivity and specificity [99].…”

Progressive cerebral injury in the setting of chronic HIV infection and antiretroviral therapy

“…There have been few MRS prospective studies reported (Kantarci et al , 2007; Olson et al , 2008; Pilatus et al , 2009; Schott et al , 2010). Metabolite levels in healthy controls acquired using similar methods as described here remain relatively unchanged over time compared to those observed in the study patient.…”

Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain

“…They found that beyond the effects of age and estimated intelligence, only NAA significantly contributed to explaining the variance in executive function. This has been supported by Kantarci et al (2002) and Olson et al [39,40]. However Valenzuela et al [30] reported an unexplained reduction in NAA/Cr measures in the hippocampus following memory training.…”