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.

1st Department of Neurology Faculty of Medicine Masaryk University and St Anne's Teaching Hospital Brno Czech Republic

Ataxia Center Cognitive Behavioural neurology Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA

Ataxia Laboratory 1 R C C S Santa Lucia Foundation Rome Italy

Center for Geriatric and Gerontology Taipei Veterans General Hospital Taipei Taiwan

Center for Healthy Longevity and Aging Sciences National Yang Ming Chiao Tung University College of Medicine Taipei Taiwan

Center for Magnetic Resonance Research University of Minnesota Minneapolis MN USA

CHNO Des Quinze Vingts INSERM DGOS CIC 1423 28 rue de Charenton 75012 Paris France

Department of Medical Education Tokyo Medical University Tokyo Japan

Department of Neurology Charles University 1st Faculty of Medicine and General University Hospital Prague Czech Republic

Department of Neurology Massachusetts General Hospital and Harvard Medical School Boston MA USA

Department of Neurology Neurological Institute Taipei Veterans General Hospital Taipei Taiwan

Department of Neurology School of Medicine University of Minnesota Minneapolis USA

Department of Paediatrics Warren Alpert Medical School of Brown University 222 Richmond St Providence RI 02903 USA

Department of Psychiatry and Behavioural Sciences University of Washington Seattle WA USA

Department of Psychological and Brain Sciences Texas A and M University 4235 TAMU College Station TX 77843 USA

Department of Psychology Georgia State University Atlanta GA USA

Department of Psychology Sapienza University of Rome Rome Italy

Department of Psychology Stavanger University Institute of Social Sciences Kjell Arholms Gate 41 4021 Stavanger Norway

Department of Psychology The Education University of Hong Kong New Territories Tai Po Hong Kong China

Faculty of Psychology and Neuroscience Department of Cognitive Neuroscience Maastricht University PO BOX 616 6200 MD Maastricht The Netherlands

Freie Universität Berlin Fachbereich Mathematik und Informatik Arnimallee 12 14195 Berlin Germany

Geriatric Research Education and Clinical Center Veteran's Affairs Medical Center Puget Sound Seattle WA USA

Gerontology Institute Georgia State University Atlanta GA USA

Gordon Center for Medical Imaging Department of Radiology Massachusetts General Hospital and Harvard Medical School Boston MA USA

Graduate School of Advanced Integrated Studies in Human Survivability Kyoto University Kyoto Japan

Jissen Women's University Tokyo Japan

King's College London Institute of Psychiatry Psychology and Neuroscience Centre for Neuroimaging Sciences Box 89 De Crespigny Park London PO SE5 8AF UK

Laboratory for Neuroanatomy and Cerebellar Neurobiology Massachusetts General Hospital and Harvard Medical School Boston MA USA

Laboratory of Neuropsychology and Human Neuroscience Department of Psychology The University of Hong Kong Hong Kong China

Noninvasive Neuromodulation Unit Experimental Therapeutics and Pathophysiology Branch National Institute of Mental Health NIH Bethesda USA

Research Center for Child Mental Development University of Fukui Fukui Japan

Rhode Island Hospital Department for Diagnostic Imaging 1 Hoppin St Providence RI 02903 USA

School for Mental Health and Neuroscience Alzheimer Centre Limburg Maastricht University PO BOX 616 6200 MD Maastricht The Netherlands

Service de Neurologie Médiathèque Jean Jacquy CHU Charleroi Charleroi Belgium

Service des Neurosciences University of Mons Mons Belgium

Sorbonne Université INSERM CNRS Institut de la Vision 17 rue Moreau F 75012 Paris France

State Key Laboratory of Brain and Cognitive Sciences The University of Hong Kong Hong Kong China

Taipei Municipal Gan Dau Hospital Taipei Taiwan

Texas A and M Institute for Neuroscience Texas A and M University College Station TX USA

United Graduate School of Child Development Osaka University Kanazawa University Hamamatsu University School of Medicine Chiba University and University of Fukui Osaka Japan

Université Côte d'Azur LAMHESS Nice France

Université Versailles St Quentin en Yvelines Paris France

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Expression of Neuronal Nicotinic Acetylcholine Receptor and Early Oxidative DNA Damage in Aging Rat Brain-The Effects of Memantine