Abstract
BackgroundCurrent demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. In this context, understanding physiological aging and its turning point into neurodegeneration is essential for the development of possible biomarkers and future therapeutics of brain disease.MethodsThe SENIOR study represents a longitudinal, observational study including cognitively healthy elderlies aged between 50 and 70 years old at the time of inclusion, being followed annually over 10 years. Our multimodal protocol includes structural, diffusion, functional, and sodium magnetic resonance imaging (MRI) at 3 T and 7 T, positron emission tomography (PET), blood samples, genetics, audiometry, and neuropsychological and neurological examinations as well as assessment of neuronal risk factors.ResultsOne hundred forty-two participants (50% females) were enrolled in the SENIOR cohort with a mean age of 60 (SD 6.3) years at baseline. Baseline results with multiple regression analyses reveal that cerebral white matter lesions can be predicted by cardiovascular and cognitive risk factors and age. Cardiovascular risk factors were strongly associated with juxtacortical and periventricular lesions. Intra-subject across-test variability as a measure of neuropsychological test performance and possible cognitive marker predicts white matter volume and is significantly associated with risk profile. Division of the cohort into subjects with a higher and lower risk profile shows significant differences in intra-subject across-test variability and volumes as well as cortical thickness of brain regions of the temporal lobe. There is no difference between the lower- and higher-risk groups in amyloid load using PET data from a subset of 81 subjects.ConclusionsWe here describe the study protocol and baseline findings of the SENIOR observational study which aim is the establishment of integrated, multiparametric maps of normal aging and the identification of early biomarkers for neurodegeneration. We show that intra-subject across-test variability as a marker of neuropsychological test performance as well as age, gender, and combined risk factors influence neuronal decline as represented by decrease in brain volume, cortical thickness, and increase in white matter lesions. Baseline findings will be used as underlying basis for the further implications of aging and neuronal degeneration as well as examination of brain aging under different aspects of brain pathology versus physiological aging.
Highlights
Current demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases
Forty-four subjects were excluded for the following reasons: failed to succeed the neuropsychological tests (n = 16), detection of structural abnormalities on magnetic resonance imaging (MRI) (n = 11), or both (n = 3), movement during MRI imaging or artifacts (n = 4), not meeting inclusion criteria referring to pre-existing diseases (n = 4), or discomfort during the imaging session (n = 3) and stopping voluntarily (n = 3)
We further demonstrate that participants with a higher combined cardiovascular and cognitive risk factor profile show a higher variability Vi and present this neuropsychological parameter as a possible early marker of brain pathology: Being part of a risk group shows altered structural patterns as reduction in volume and cortical thickness in brain regions of the temporal lobe sensitive to neurodegeneration
Summary
Current demographic trends point towards an aging society entailing increasing occurrence and burden of neurodegenerative diseases. Autopsy studies on elderly subjects who have not been diagnosed with a neurodegenerative disease reported tau and amyloid deposits [9, 10] and it still stays unclear what causes these deposits and what are their contributions to neurodegeneration Both the likeliness and extent of cerebral volumetric changes and other structural alterations increase with old age and can be influenced by intrinsic and extrinsic factors such as cardiovascular risk profile [11,12,13], but their role in the aging process is still the topic of current research [6, 14]. Studies so far have clearly pointed to a highly increased inter-individual variability of brain aging underlining the importance of exploration and definition of physiological aging in delimitation to cerebral pathology
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
