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Background Current 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. Methods The 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. Results One 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. Conclusions We 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.

Alzheimer's & dementia / Translational research & clinical interventions 6(1), e12032 (2020). doi:10.1002/trc2.12032, Published by Wiley, Hoboken, NJ

Current treatment in late-life cognitive impairment and dementia is still limited, and there is no cure for brain tissue degeneration or reversal of cognitive decline. Physical activity represents a promising non-pharmacological interventional approach in many diseases causing cognitive impairment, but its effect on brain integrity is still largely unknown. Especially research of cerebral alterations in disease state that goes beyond observations of clinical improvement is crucial to understand disease processes and possible effective treatments. In this systematic review, we address the question how physical activity and fitness in mild cognitive impairment (MCI) and Alzheimer's disease (AD) influences brain architecture compared to cognitively healthy elderly. We review both interventional studies comprising aerobic, coordinative and resistance exercises and observational studies on fitness and physical activity combined with Magnetic Resonance imaging (MRI). Different MRI approaches were included such as volumetric and structural analyses, Diffusion Tensor Imaging (DTI), functional MRI and Cerebral Blood Flow (CBF). We evaluate MRI results for different exercise modalities and performed a methodological evaluation of interventional studies in cognitive decline compared to normal aging. According to our results, among 12 interventions in AD/MCI, aerobic exercise is most frequently applied (9 studies). Interventions in AD/MCI altogether reveal a higher methodological quality compared to interventions in healthy elderly (8.33 ± 2.19 vs. 6.25 ± 2.36 out of 13 points), with most frequent missing aspects related to descriptions of complications, lack of intention-to-treat and statistical power analyses. Effects of aerobic exercise and fitness seem to mainly impact brain structures sensitive to neurodegeneration, which especially comprise frontal, temporal and parietal regions, such as the hippocampal/parahippocampal region, precuneus, anterior cingulate and prefrontal cortex, which are reported by several studies. General fitness measured via an objective fitness assessment and questionnaires seems to have a more global cerebral effect, probably due to its long-term application, whereas distinct intervention effects of durations between 3 and 6 months seem to concentrate on more local brain regions as the hippocampus, which can also be influenced by region of interest analyses. There is still a lack of evidence on other or combined types of intervention modalities, such as resistance, coordinative as well as multicomponent exercise during cognitive decline, and complex interventions as dancing. Future research should examine their beneficial effect on brain integrity, since several non-MRI studies already point to their advantageous impact. As a further future prospect, combination and application of newly developed imaging methods such as metabolic imaging should be envisaged to understand physical activity and its cerebral influence under its many-sided facets., Highlights • 23 studies on physical activity in cognitive decline applying MRI were included. • Exercise in cognitive decline impacts brain regions sensitive to neurodegeneration. • These regions mainly comprise parietal, frontal and temporal brain regions. • Interventions in MCI show higher methodological quality than in healthy aging. • More studies on alternative intervention forms and metabolic imaging are needed.