Innovative Molecular Imaging for Clinical Research, Therapeutic Stratification, and Nosography in Neuroscience.

Over the past few decades, several radiotracers have been developed for neuroimaging applications, especially in PET. Because of their low steric hindrance, PET radionuclides can be used to label molecules that are small enough to cross the blood brain barrier, without modifying their biological properties. As the use of 11C is limited by its short physical half-life (20 min), there has been an increasing focus on developing tracers labeled with 18F for clinical use. The first such tracers allowed cerebral blood flow and glucose metabolism to be measured, and the development of molecular imaging has since enabled to focus more closely on specific targets such as receptors, neurotransmitter transporters, and other proteins. Hence, PET and SPECT biomarkers have become indispensable for innovative clinical research. Currently, the treatment options for a number of pathologies, notably neurodegenerative diseases, remain only supportive and symptomatic. Treatments that slow down or reverse disease progression are therefore the subject of numerous studies, in which molecular imaging is proving to be a powerful tool. PET and SPECT biomarkers already make it possible to diagnose several neurological diseases in vivo and at preclinical stages, yielding topographic, and quantitative data about the target. As a result, they can be used for assessing patients' eligibility for new treatments, or for treatment follow-up. The aim of the present review was to map major innovative radiotracers used in neuroscience, and explain their contribution to clinical research. We categorized them according to their target: dopaminergic, cholinergic or serotoninergic systems, β-amyloid plaques, tau protein, neuroinflammation, glutamate or GABA receptors, or α-synuclein. Most neurological disorders, and indeed mental disorders, involve the dysfunction of one or more of these targets. Combinations of molecular imaging biomarkers can afford us a better understanding of the mechanisms underlying disease development over time, and contribute to early detection/screening, diagnosis, therapy delivery/monitoring, and treatment follow-up in both research and clinical settings

Cross-Sectional and Prospective Associations Between β-Amyloid in the Brain and Chair Rise Performance in Nondementia Older Adults With Spontaneous Memory Complaints

BACKGROUND: The objectives of this study were to examine the cross-sectional and prospective associations of muscle functional performance as assessed by a chair rise test and brain amyloid load among nondemented older adults with spontaneous memory complaints. METHODS: This is a secondary analysis, with an observational design, using data from the MAPT randomized controlled trial. Individuals assessed for brain amyloid load (florbetapir F18 positron emission tomography) and without clinical dementia (N = 269 aged 75.2±4.2 years; 60.2% women) participated in the study. Cortical and regional standard uptake value ratios (SUVRs) were obtained. The main outcome measure was the 5-repetition chair rise performance (maximum speed-higher is better), which was assessed at baseline and at 6, 12, 24, and 36 months. Adjusted multiple linear (cross-sectional) and mixed-effect (overtime) regressions were performed. RESULTS: Any of mean cortical (regions of interest) and each regional SUVRs (anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval center, and temporal cortex) were not associated to chair rise after adjustment for multiplicity. These findings were obtained for both cross-sectional and prospective associations. CONCLUSIONS: Brain amyloid was not found to be associated to chair rise performance in nondemented older adults with memory complaints. Potential mechanisms on the links, if any, of amyloid load with physical performance are probably not dependent on muscle function

Cross-Sectional and Prospective Associations Between β-Amyloid in the Brain and Chair Rise Performance in Nondementia Older Adults With Spontaneous Memory Complaints

BACKGROUND: The objectives of this study were to examine the cross-sectional and prospective associations of muscle functional performance as assessed by a chair rise test and brain amyloid load among nondemented older adults with spontaneous memory complaints. METHODS: This is a secondary analysis, with an observational design, using data from the MAPT randomized controlled trial. Individuals assessed for brain amyloid load (florbetapir F18 positron emission tomography) and without clinical dementia (N = 269 aged 75.2\ub14.2 years; 60.2% women) participated in the study. Cortical and regional standard uptake value ratios (SUVRs) were obtained. The main outcome measure was the 5-repetition chair rise performance (maximum speed-higher is better), which was assessed at baseline and at 6, 12, 24, and 36 months. Adjusted multiple linear (cross-sectional) and mixed-effect (overtime) regressions were performed. RESULTS: Any of mean cortical (regions of interest) and each regional SUVRs (anterior cingulate, anterior putamen, caudate, hippocampus, medial orbitofrontal cortex, occipital cortex, parietal cortex, pons, posterior cingulate, posterior putamen, precuneus, semioval center, and temporal cortex) were not associated to chair rise after adjustment for multiplicity. These findings were obtained for both cross-sectional and prospective associations. CONCLUSIONS: Brain amyloid was not found to be associated to chair rise performance in nondemented older adults with memory complaints. Potential mechanisms on the links, if any, of amyloid load with physical performance are probably not dependent on muscle function

Cross-sectional associations of total plasma homocysteine with cortical β-amyloid independently and as a function of omega 3 polyunsaturated fatty acid status in older adults at risk of dementia

Objectives: Elevated total plasma homocysteine is a risk factor for Alzheimer\ue2\u80\u99s disease (AD) and there is some evidence that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can modulate the effects of homocysteine-lowering B vitamins on AD related pathologies. Hence we investigated the relationship between total plasma homocysteine and cortical \uce\ub2-amyloid (A\uce\ub2) in older adults at risk of dementia. The role of erythrocyte membrane n-3 PUFAs (omega 3 index) on this relationship was also explored. Design: This is a cross-sectional study using data from the Multidomain Alzheimer Preventive Trial (MAPT); a randomised controlled trial. Setting: French community dwellers aged 70 or over reporting subjective memory complaints, but free from a diagnosis of clinical dementia. Participants: Individuals were from the MAPT trial (n = 177) with data on total plasma homocysteine at baseline and cortical A\uce\ub2 load. Measurements: Cortical-to-cerebellar standard uptake value ratios were assessed using [18F] florbetapir positron emission tomography (PET). Total baseline plasma homocysteine was measured using an enzymatic cycling assay. Baseline omega 3 index was measured using gas chromatography. Cross-sectional associations were explored using adjusted multiple linear regression models. Results: We found that total baseline plasma homocysteine was not significantly associated with cortical A\uce\ub2 as demonstrated using multiple linear regression models adjusted for age, sex, education, cognitive status, time interval between baseline and PET-scan, omega-3 index, MAPT group allocation and Apolipoprotein E \uce\ub54 status (B-coefficient -0.001, 95 % CI: -0.008,0.006, p = 0.838). Exploratory analysis showed that homocysteine was however significantly associated with cortical A\uce\ub2 in subjects with low baseline omega-3 index (< 4.72 %) after adjustment for Apolipoprotein E \uce\ub54 status (B-coefficient 0.041, 95 % CI: 0.017,0.066, p = 0.005, n = 10), but not in subjects with a high baseline omega-3 index (B-coefficient -0.010, 95 % CI: -0.023,0.003, p = 0.132, n = 66). Conclusions: The role of n-3 PUFAs on the relationship between homocysteine and cerebral A\uce\ub2 warrants further investigation

Functional connectivity and cognitive changes after donepezil treatment in healthy participants

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