Ageing is a complex phenomenon affecting a wide range of coexisting biological processes. The homogeneity of the studied population is an essential parameter for valid interpretations of outcomes. The presented study capitalises on the MRI data available in the Human Connectome Project-Aging (HCP-A) and, within individuals over 55 years of age who passed the HCP-A section criteria, compares a subgroup of 37 apparently neurocognitively healthy individuals selected based on stringent criteria with 37 age and sex-matched individuals still representative of typical ageing but who did not pass the stringent definition of neurocognitively healthy. Specifically, structural scans, diffusion weighted imaging and T1w/T2w ratio were utilised. Furthermore, data of 26 HCP-A participants older than 90 years as notional 'super-agers' were analysed. The relationship of age and several microstructural MRI metrics (T1w/T2w ratio, mean diffusivity, intracellular volume fraction and free water volume fraction) differed significantly between typical and healthy ageing cohort in areas highly relevant for ageing such as hippocampus, prefrontal and temporal cortex and cerebellum. However, the trajectories of the healthy ageing population did not show substantially better overlap with the findings in people older than 90 than those of the typical population. Therefore, caution must be exercised in the choice of adequate study group characteristics relevant for respective ageing-related hypotheses. Contrary to typical ageing group, the healthy ageing cohort may show generally stable levels of several MRI metrics of interest.

• Keywords
• HCP‐A, MRI, healthy ageing, typical ageing,
• MeSH
• Cognition * physiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain diagnostic imaging   MeSH
• Gray Matter * diagnostic imaging   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Aging * physiology   MeSH
• Healthy Aging physiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

• Keywords
• Affective, Aging, Alzheimer’s Disease, Cerebellum, Cognitive, Motor,
• MeSH
• Depressive Disorder, Major * MeSH
• Adult MeSH
• Consensus MeSH
• Quality of Life MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Cerebellum pathology   MeSH
• Cross-Sectional Studies MeSH
• Aged MeSH
• Aging MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The advent of new, advanced quantitative MRI metrics allows for in vivo evaluation of multiple biological processes highly relevant for ageing. The presented study combines several MRI parameters hypothesised to detect distinct biological characteristics as myelin density, cellularity, cellular membrane integrity and iron concentration. 116 healthy volunteers, continuously distributed over the whole adult age span, underwent a multi-modal MRI protocol acquisition. Scatterplots of individual MRI metrics revealed that certain MRI protocols offer much higher sensitivity to early adulthood changes while plateauing in higher age (e.g., global functional connectivity in cerebral cortex or orientation dispersion index in white matter), while other MRI metrics provided reverse ability-stable levels in young adulthood with sharp changes with rising age (e.g., T1ρ and T2ρ). Nonetheless, despite the previously published validations of specificity towards microstructural biology based on cytoarchitectonic maps in healthy population or alterations in certain pathologies, several metrics previously hypothesised to be selective to common measures failed to show similar scatterplot distributions, pointing to further confounding factors directly related to age. Furthermore, other metrics, previously shown to detect different biological characteristics, exhibited substantial intercorrelations, be it due to the nature of the MRI protocol itself or co-dependence of relevant biological microstructural processes. All in all, the presented study provides a unique basis for the design and choice of relevant MRI parameters depending on the age group of interest. Furthermore, it calls for caution in simplistic biological inferences in ageing based on one simple MRI metric, even though previously validated under other conditions. Complex multi-modal approaches combining several metrics to extract the shared subcomponent will be necessary to achieve the desired goal of histological MRI.

• Keywords
• ageing, diffusion weighted imaging, quantitative MRI, resting state functional MRI, rotating frame relaxometry,
• Publication type
• Journal Article MeSH

The possibilities of substantial long-term improvement of predictive timing might be sometimes seen as limited, with scanty information of neural substrates underlying the potential learning process. To address this issue, we have investigated the performance of 21 baseball professionals and 21 matched controls in a predictive motor timing task previously shown to engage the cerebellum. Baseball players, hypothesized as a model of overtraining of the prediction of future state of the surroundings, showed significantly higher quantitative performance than nonathletic controls, with a substantial part of the baseball players reaching levels far beyond the range observed in common population. Furthermore, the qualitative performance profile of baseball players under various conditions as target speed and acceleration modes did not differ from the profile of healthy controls. Our results suggest that regular exigent training has the potential to vastly improve predictive motor timing. Moreover, the quantitative but not qualitative difference in the performance profile allows us to hypothesize that the selective honing of the same cerebellar processes and networks as in non-trained individuals is the substrate for the quantitative performance improvement, without substantial engagement of further neural nodes.

• Keywords
• Cerebellar learning, Cerebellum, Overtraining, Predictive motor timing,
• MeSH
• Baseball MeSH
• Exercise physiology   MeSH
• Adult MeSH
• Humans MeSH
• Brain physiology   MeSH
• Psychomotor Performance physiology   MeSH
• Athletes * MeSH
• Learning physiology   MeSH
• Time Perception physiology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH