Magnetic resonance spectroscopy, β-amyloid load, and cognition in a population-based sample of cognitively normal older adults

Objective: To determine the relationship between proton magnetic resonance spectroscopy (¹H MRS) metabolites and β-amyloid (Aβ) load and the effects of Aβ load on the association between ¹H MRS metabolites and cognitive function in cognitively normal older adults. Methods: We studied 311 cognitively normal older adults who participated in the populationbased Mayo Clinic Study of Aging from January 2009 through September 2010. Participants underwent ¹¹C-Pittsburgh compound B (PiB) PET, ¹H MRS from the posterior cingulate gyri, and neuropsychometric testing to assess memory, attention/executive, language, and visual-spatial domain functions within 6 months. Partial Spearman rank order correlations were adjusted for age, sex, and education. Results: Higher PiB retention was associated with abnormal elevations in myoinositol (mI)/creatine (Cr) (partial r_s = 0.17; p = 0.003) and choline (Cho)/Cr (partial r_s = 0.13; p = 0.022) ratios. Higher Cho/Cr was associated with worse performance on Auditory Verbal Learning Test Delayed Recall (partial r_s = -0.12; p = 0.04), Trail Making Test Part B (partial r_s = 0.12; p = 0.04), Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol (partial r _s = -0.18; p < 0.01), and WAIS-R Block Design (partial r _s=-0.12; p = 0.03). Associations between ¹H MRS metabolites and cognitive function were not different among participants with high vs low PiB retention. Conclusion: In cognitively normal older adults, the 1H MRS metabolite ratios mI/Cr and Cho/Cr are associated with the preclinical pathologic processes in the Alzheimer disease cascade. Higher Cho/Cr is associated with worse performance on domain-specific cognitive tests independent of Aβ load, suggesting that Cho/Cr elevation may also be dependent on other preclinical dementia pathologies characterized by Cho/Cr elevation such as Lewy body or ischemic vascular disease in addition to Aβ load.