The Cognitive Cerebellum in Aging and Dementia

 
   Lead Investigator:    Erik Carlson
   Institution      :    University of Washington/ VA Puget Sound
   E-Mail           :    erikcarlson1@gmail.com
   Proposal ID      :    1114



   Proposal Description:
   In the context of aging and neurodegeneration, the cerebellum is an enigma. Genetic markers of cellular aging in cerebellum accumulate more slowly than in the rest of the brain, and it generates unknown factors that may slow or even reverse neurodegenerative pathology in animal models of Alzheimer?s Disease (AD). Cerebellum shows increased activity in early Parkinson?s disease (PD), suggesting a compensatory function that may mitigate symptoms early in PD pathophysiology. Perhaps most notably, different parts of the brain accumulate neuropathological markers of AD in a recognized progression and generally, cerebellum is the last brain region to do so.     Conversely, cerebellar pathology in neurodegenerative disorders is strongly associated with cognitive dysfunction. In neurodegenerative or neurological disorders where cerebellum is directly implicated, such as spinocerebellar ataxia, cerebellar cortical atrophy, posterior cerebellar infarcts, and essential tremor, rates of cognitive dysfunction, dementia and neuropsychiatric symptoms are increased. When the cerebellum shows AD pathology, such as in familial AD, it is associated with earlier onset and greater severity of disease.  The cerebellum is well known for comparing internal representations of information with observed outcomes and providing real-time feedback to cortical regions, a critical function that is disturbed in neuropsychiatric disorders such as intellectual disability, schizophrenia, dementia, and autism, and         required for cognitive domains such as working memory. While cerebellum has reciprocal connections with non-motor brain regions and likely plays a role in complex, goal-directed behaviors, it has proven difficult to establish what it does mechanistically to modulate these behaviors. Due to this lack of             understanding, it?s not surprising to see the cerebellum reflexively dismissed or even ignored in basic and translational neuropsychiatric literature.    Aim 1. Determine w