Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer’s disease: a systematic review

Abstract

BackgroundNeuroimaging-biomarkers of Mild Cognitive Impairment (MCI) allow an early diagnosis in preclinical stages of Alzheimer’s disease (AD). The goal in this paper was to review of biomarkers for Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD), with emphasis on neuroimaging biomarkers.MethodsA systematic review was conducted from existing literature that draws on markers and evidence for new measurement techniques of neuroimaging in AD, MCI and non-demented subjects. Selection criteria included: 1) age ≥ 60 years; 2) diagnosis of AD according to NIAAA criteria, 3) diagnosis of MCI according to NIAAA criteria with a confirmed progression to AD assessed by clinical follow-up, and 4) acceptable clinical measures of cognitive impairment, disability, quality of life, and global clinical assessments.ResultsSeventy-two articles were included in the review. With the development of new radioligands of neuroimaging, today it is possible to measure different aspects of AD neuropathology, early diagnosis of MCI and AD become probable from preclinical stage of AD to AD dementia and non-AD dementia.ConclusionsThe panel of noninvasive neuroimaging-biomarkers reviewed provides a set methods to measure brain structural and functional pathophysiological changes in vivo, which are closely associated with preclinical AD, MCI and non-AD dementia. The dynamic measures of these imaging biomarkers are used to predict the disease progression in the early stages and improve the assessment of therapeutic efficacy in these diseases in future clinical trials.

The potential of neurofilaments analysis using dry-blood and plasma spots

“…CSF, the main repository of by-products of neuronal destruction, is enriched in Nf and unlike other peptides linked to neurodegeneration such as Tau and Amyloid beta, Nf expression in CSF is highly correlated to that in blood 5,6 . As serial lumbar punctures to procure CSF for biomarkers analysis may be impractical in advanced and uncooperative patients and disease monitoring by structural and functional brain imaging is expensive and logistically complex 7 , blood may represent the ideal source to track any meaningful disease signal of neurodegeneration cost-effectively in large biomarkers studies and clinical trials. Both light and heavy neurofilament chain (Nf-L; Nf-H) measurement in blood is now possible thanks to highly sensitive immunodetection platforms like Meso Scale Discovery (MSD) and single molecular array (Simoa), which provide readings at picogram and femptogram levels respectively 3,[8][9][10] .…”

Complexity across scales: a walkthrough to linking neuro-imaging readouts to molecular processes

“…Similarly, [18 F] fludeoxyglucose-positron emission tomography (FDG-PET) detects bilateral temporoparietal hypometabolism [56][57][58]. They have been widely used as a diagnostic differential biomarker discriminating between patients with AD dementia and vascular dementia [59,60]. Another radioisotope based biomarker that is widely used in diagnostic studies is C-labeled Pittsburgh Compound-B ([(11)C]PIB).…”

“…Imaging techniques such as SPECT and DTI enable early detection of hypoperfusion in the white matter and cortex [63,64]. Abnormal cerebral perfusion are clear indicators of diagnostic transition from MCI to AD [65,66].…”

Evaluation of Brain Tortuosity Measurement for the Automatic Multimodal Classification of Subjects with Alzheimer’s Disease

“…It has been reported that this illness gradually provokes changes in brain morphology, leading to loss of cognitive activities such as memory, orientation, and language. It is related to aging and represents between 50% and 75% of all cases of dementia in global population [1]. e clinical criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA) generally recognize three phases principal of the progression of AD [2]: preclinical healthy stage, mild cognitive impairment (MCI), and dementia due to AD.…”