![]() ![]() In contrast, “crystallized skills,” such as vocabulary and fund of knowledge, which are overlearned, practiced, and enhanced by experience, typically demonstrate greater stability throughout the lifespan ( 6). In aggregate, so-called “fluid skills” such as processing speed, memory, and reasoning, which rely on integration of new information, speeded response, and problem solving, tend to decrease more saliently ( 5). Individual cognitive domains vary with regard to their underlying neuroanatomical substrates and may decline at different rates within individuals. Rather than a precipitous drop in old age, multivariate growth curve models have demonstrated small yet consistent diminishment in abilities across the lifespan ( 7). Cognitive changes across the lifespanĪs early as the third decade of life, core cognitive abilities, including processing speed, reasoning, episodic memory, and spatial visualization, begin to decline ( 6). Here we provide a concise overview of brain structure and function changes across the human lifespan, and mechanistic insights from translational studies highlighting biological aging processes as propagators of cognitive decline and neurodegenerative disease. Even among older adults who remain free of dementia throughout their lives, cognitive decline and neurodegenerative changes are appreciable with advancing age ( 5), suggesting shared pathophysiological mechanisms. After the age of 65, the incidence of ADRD nearly doubles every 5 years, and by the ninth decade of life, approximately one of every three adults meets criteria for dementia ( 4). As with many chronic conditions, aging is the greatest risk factor for the development of ADRD. ![]() Alzheimer’s disease and related dementias (ADRD), which induce progressive cognitive and functional impairment, are among the top contributors to disability and mortality ( 3). As a consequence, the prevention and treatment of chronic age-related diseases are of growing public health significance ( 2). Introductionīy 2030, an estimated one in five Americans will be 65 years of age or older ( 1). Collaboration across the fields of geroscience and neuroscience, coupled with the development of new translational animal models that more closely align with human disease processes, is necessary to advance novel therapeutic discovery in this realm. Targeting fundamental processes underlying biological aging may represent a yet relatively unexplored avenue to attenuate both age-related cognitive decline and ADRD. We summarize research across clinical and translational studies to link biological aging processes to underlying ADRD pathogenesis. Next, we highlight selected aging processes that are differentially regulated in neurodegenerative disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular dysfunction, inflammation, and lipid dysregulation. In this Review, we provide an overview of changes in cognition, brain morphology, and neuropathological protein accumulation across the lifespan in humans, with complementary and mechanistic evidence from animal models. Even among older adults who remain free of dementia throughout their lives, cognitive decline and neurodegenerative changes are appreciable with advancing age, suggesting shared pathophysiological mechanisms. As with many chronic conditions, aging is the single most influential factor in the development of ADRD. Alzheimer’s disease and related dementias (ADRD) are among the top contributors to disability and mortality in later life.
0 Comments
Leave a Reply. |
Details
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |