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

IntroductionMild 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.MethodsNinety-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.ResultsBoth 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.ConclusionWhile 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.

Precuneus Structure Changes in Amnestic Mild Cognitive Impairment

“…15,28 Coutinho and colleagues hypothesize that precuneus hypometabolism would be more specific for patients with aMCI, whereas additional frontal hypometabolism is associated with the non-aMCI subtype. 16 Although we cannot directly compare our findings with PET data, our results suggest structural network changes in patients with aMCI involve the precuneus, frontal, and temporal brain regions. Additional structural MRI investigations of non-aMCI patients would be necessary to differentiate brain changes across MCI subtypes.…”

“…18 Positron-emission tomography studies demonstrate hypometabolic changes as well as a high susceptibility to amyloid deposition in the precuneus of patients with aMCI. [14][15][16] These changes are embedded into a network of metabolic alterations not only in medial temporal but also in frontal brain regions. 14,15,18 Using high-resolution MRI and whole-brain cortical thickness analyses, our aim was to investigate whether these network characteristics can be detected in structural brain imaging data as well.…”

Micro RNA’s (mirna’s) may help explain expression of multiple genes in Alzheimer’s Frontal Cortex

“…Individuals with MCI have ~50% chance of progressing into AD dementia over 3-5 years and demonstrate impaired cerebral cortical glucose metabolism [3][4][5][6][7][8][9][10][11] and increased oxidative stress damage products [12]. These findings suggest an early impairment of bioenergetic function potentially arising from oxidative stress damage.…”

[18F]THK5351 PET Imaging in Patients with Mild Cognitive Impairment

“…63 However, studies have shown that naMCI patients are more likely to have low Pittsburgh Compound B (PiB) retention and higher β-amyloid levels in the CSF. 64,65 It has also been shown that there are no significant differences in the hippocampal volume, cortical thickness, and hippocampal metabolism between amyloid-negative MCI patients and elderly controls, with the CSF levels of p-tau and t-tau being lower and the longitudinal cognitive performance being better in amyloid-negative MCI patients than in amyloid-positive MCI patients. 22,66 The finding of greater [ 18 F]THK5351 retention in the present aMCI group might have been due to a trend for greater amyloid positivity in that group compared to the naMCI group.…”