Brain metabolism and cerebrospinal fluid biomarkers profile of non-amnestic mild cognitive impairment in comparison to amnestic mild cognitive impairment and normal older subjects

Abstract

Introduction: Mild cognitive impairment (MCI) is classically considered a transitional stage between normal aging and dementia. Non-amnestic MCI (naMCI) patients, however, typically demonstrate cognitive deficits other than memory decline. Furthermore, as a group, naMCI have a lower rate of an eventual dementia diagnosis as compared to amnestic subtypes of MCI (aMCI). Unfortunately, studies investigating biomarker profiles of naMCI are scarce. The study objective was to investigate the regional brain glucose metabolism (rBGM) with [18F]FDG-PET and cerebrospinal fluid (CSF) biomarkers in subjects with naMCI as compared to a control group (CG) and aMCI subjects.

Methods: Ninety-five patients were included in three different groups: naMCI (N = 32), aMCI (N = 33) and CG (N = 30). Patients underwent brain MRI and [18F]FDG-PET. A subsample (naMCI = 26, aMCI = 28) also had an assessment of amyloid-β, tau, and phosphorylated tau levels in the CSF.

Results: Both MCI groups had lower rBGM in relation to the CG in the precuneus. Subjects with naMCI showed decreased right prefrontal metabolism as well as higher levels of CSF amyloid-β relative to aMCI subjects.

Conclusion: While amnestic MCI subjects showed a biomarker profile classically related to MCI due to Alzheimer's disease, naMCI patients illustrated a decrease in both prefrontal hypometabolism and higher CSF amyloid-β levels relative to the aMCI group. These biomarker findings indicate that naMCI is probably a heterogeneous group with similar precuneus hypometabolism compared to aMCI, but additional frontal hypometabolism and less amyloid-β deposition in the brain. Clinical follow-up and reappraisal of biomarkers of the naMCI group is needed to determine the outcome and probable etiological diagnosis.

Fig. 1

Box-plot graphics for CSF biomarkers and mean radioactive counts. a Z scores for CSF Aβ, tau, p-tau, and p-tau/Aβ ratio proteins in each group. b Mean radioactive counts in the three areas of the precuneus which presented rBGM differences between aMCI and CG (PREC_area 1 and 2) and naMCI and CG (PREC_area 3). ^•1.5 times the interquartile range, *more than 1.5 times the interquartile range; ⁺value is actually 5.1 SD (outlier). aMCI amnestic mild cognitive impairment, CG control group, naMCI nonamnestic mild cognitive impairment, p-tau phosphorylated tau

Fig. 2

Illustrative anatomic localization of the peak voxels of rBGM reductions as measured with [¹⁸F]-FDG-PET. a1, a2 naMCI rBGM reductions in relation to the CG, predominantly in right prefrontal areas but also in the precuneus and a left prefrontal area without statistic significance; a3 naMCI rBGM reductions in relation to the aMCI group (right prefrontal area). b1, b2 Bilateral metabolic reduction in the precuneus, parietal, and temporal cortex is seen in the aMCI group in comparison with normal older subjects; b3 hypometabolism is also noted in the left temporal lobe in aMCI in relation to naMCI