Reappraisal of the Concept of Accelerated Aging in Neurodegeneration and Beyond.

BACKGROUND: Genetic and epigenetic changes, oxidative stress and inflammation influence the rate of aging, which diseases, lifestyle and environmental factors can further accelerate. In accelerated aging (AA), the biological age exceeds the chronological age. OBJECTIVE: The objective of this study is to reappraise the AA concept critically, considering its weaknesses and limitations. METHODS: We reviewed more than 300 recent articles dealing with the physiology of brain aging and neurodegeneration pathophysiology. RESULTS: (1) Application of the AA concept to individual organs outside the brain is challenging as organs of different systems age at different rates. (2) There is a need to consider the deceleration of aging due to the potential use of the individual structure-functional reserves. The latter can be restored by pharmacological and/or cognitive therapy, environment, etc. (3) The AA concept lacks both standardised terminology and methodology. (4) Changes in specific molecular biomarkers (MBM) reflect aging-related processes; however, numerous MBM candidates should be validated to consolidate the AA theory. (5) The exact nature of many potential causal factors, biological outcomes and interactions between the former and the latter remain largely unclear. CONCLUSIONS: Although AA is commonly recognised as a perspective theory, it still suffers from a number of gaps and limitations that assume the necessity for an updated AA concept.

Multimodal diagnostics in multiple sclerosis: predicting disability and conversion from relapsing-remitting to secondary progressive disease course - protocol for systematic review and meta-analysis.

BACKGROUND: The number of patients diagnosed with multiple sclerosis (MS) has increased significantly over the last decade. The challenge is to identify the transition from relapsing-remitting to secondary progressive MS. Since available methods to examine patients with MS are limited, both the diagnostics and prognostication of disease progression would benefit from the multimodal approach. The latter combines the evidence obtained from disparate radiologic modalities, neurophysiological evaluation, cognitive assessment and molecular diagnostics. In this systematic review we will analyse the advantages of multimodal studies in predicting the risk of conversion to secondary progressive MS. METHODS AND ANALYSIS: We will use peer-reviewed publications available in Web of Science, Medline/PubMed, Scopus, Embase and CINAHL databases. In vivo studies reporting the predictive value of diagnostic methods will be considered. Selected publications will be processed through Covidence software for automatic deduplication and blind screening. Two reviewers will use a predefined template to extract the data from eligible studies. We will analyse the performance metrics (1) for the classification models reflecting the risk of secondary progression: sensitivity, specificity, accuracy, area under the receiver operating characteristic curve, positive and negative predictive values; (2) for the regression models forecasting disability scores: the ratio of mean absolute error to the range of values. Then, we will create ranking charts representing performance of the algorithms for calculating disability level and MS progression. Finally, we will compare the predictive power of radiological and radiomical correlates of clinical disability and cognitive impairment in patients with MS. ETHICS AND DISSEMINATION: The study does not require ethical approval because we will analyse publicly available literature. The project results will be published in a peer-review journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42022354179.

Unraveling Lifelong Brain Morphometric Dynamics: A Protocol for Systematic Review and Meta-Analysis in Healthy Neurodevelopment and Ageing.

A high incidence and prevalence of neurodegenerative diseases and neurodevelopmental disorders justify the necessity of well-defined criteria for diagnosing these pathologies from brain imaging findings. No easy-to-apply quantitative markers of abnormal brain development and ageing are available. We aim to find the characteristic features of non-pathological development and degeneration in distinct brain structures and to work out a precise descriptive model of brain morphometry in age groups. We will use four biomedical databases to acquire original peer-reviewed publications on brain structural changes occurring throughout the human life-span. Selected publications will be uploaded to Covidence systematic review software for automatic deduplication and blinded screening. Afterwards, we will manually review the titles, abstracts, and full texts to identify the papers matching eligibility criteria. The relevant data will be extracted to a 'Summary of findings' table. This will allow us to calculate the annual rate of change in the volume or thickness of brain structures and to model the lifelong dynamics in the morphometry data. Finally, we will adjust the loss of weight/thickness in specific brain areas to the total intracranial volume. The systematic review will synthesise knowledge on structural brain change across the life-span.

Patterns of structure-function association in normal aging and in Alzheimer's disease: Screening for mild cognitive impairment and dementia with ML regression and classification models.

Background: The combined analysis of imaging and functional modalities is supposed to improve diagnostics of neurodegenerative diseases with advanced data science techniques. Objective: To get an insight into normal and accelerated brain aging by developing the machine learning models that predict individual performance in neuropsychological and cognitive tests from brain MRI. With these models we endeavor to look for patterns of brain structure-function association (SFA) indicative of mild cognitive impairment (MCI) and Alzheimer's dementia. Materials and methods: We explored the age-related variability of cognitive and neuropsychological test scores in normal and accelerated aging and constructed regression models predicting functional performance in cognitive tests from brain radiomics data. The models were trained on the three study cohorts from ADNI dataset-cognitively normal individuals, patients with MCI or dementia-separately. We also looked for significant correlations between cortical parcellation volumes and test scores in the cohorts to investigate neuroanatomical differences in relation to cognitive status. Finally, we worked out an approach for the classification of the examinees according to the pattern of structure-function associations into the cohorts of the cognitively normal elderly and patients with MCI or dementia. Results: In the healthy population, the global cognitive functioning slightly changes with age. It also remains stable across the disease course in the majority of cases. In healthy adults and patients with MCI or dementia, the trendlines of performance in digit symbol substitution test and trail making test converge at the approximated point of 100 years of age. According to the SFA pattern, we distinguish three cohorts: the cognitively normal elderly, patients with MCI, and dementia. The highest accuracy is achieved with the model trained to predict the mini-mental state examination score from voxel-based morphometry data. The application of the majority voting technique to models predicting results in cognitive tests improved the classification performance up to 91.95% true positive rate for healthy participants, 86.21%-for MCI and 80.18%-for dementia cases. Conclusion: The machine learning model, when trained on the cases of this of that group, describes a disease-specific SFA pattern. The pattern serves as a "stamp" of the disease reflected by the model.