Sleep, physical activity, sedentary behavior, and risk of incident dementia: a prospective cohort study of 431,924 UK Biobank participants

Demand Coupling Drives Neurodegeneration: A Model of Age-Related Cognitive Decline and Dementia

“…The environmental component of ARCD and ARD is well-established in large cohort studies in multiple countries but has yet to form the basis of ARD prevention or treatment policies [ 10 , 37 , 38 , 39 , 40 ]. This includes significantly increased risk of ARCD and ARD as well as worse cognitive function associated with sedentary behavior and reduced physical activity [ 37 , 41 , 42 , 43 ], chronic sleep deprivation or sleep disruption [ 37 , 44 , 45 ], insulin resistance and dysglycemia [ 46 , 47 ], poor-quality nutrition and associated changes in nutrient status [ 10 , 48 ], body composition [ 49 , 50 , 51 , 52 ], sex hormone status during and after the menopausal transition [ 53 ], and the effect of social isolation and poor social support [ 54 ]. Early evidence is mounting to suggest that lifestyle and environmental modification has the potential to prevent or even reverse ARD, especially when initiated early in the ARCD process [ 10 , 55 , 56 , 57 ].…”

“…This pathogenetic model underscores the critical need for sleep in the preservation of brain health given its central role in waste clearance, tissue repair, and plastic reorganization in response to cognitive challenge [ 142 , 143 , 144 , 145 ]. The critical role of sleep in facilitating demand–function responses accounts for the emerging evidence of a significant association between poor sleep and a heightened risk of cognitive decline and dementia [ 37 , 44 , 45 , 146 , 147 , 148 ].…”

“…This theoretical model allows for direct, simple, and equitable intervention points, as well as the possibility of improved outcomes in future pharmaceutical trials via inclusion of a holistic strategy that incorporates a component of cognitive demand to drive neurological homeostasis and repair. It also highlights the importance of a lifelong program of ongoing cognitive challenge coupled with diet and lifestyle factors, such as nutrient adequacy and sleep [ 37 , 44 , 48 , 154 ], that support the tissue-preserving adaptations those challenges stimulate. As the burden of AD is projected to cripple healthcare systems worldwide in the coming decades, we believe that this critical reappraisal of our approach is essential to maximizing our odds of success in preventing and treating the most prevalent forms of age-related cognitive decline and dementia.…”

Is the lack of appropriate cognitive demand the primary driver of dementia risk?

“…When discussing the demand model of ARD with clinicians and researchers with expertise in dementia and neurogenerative conditions, it has not been uncommon for them to ask about other established risk factors, particularly those related to general health and the environment. We must therefore make it very clear that we believe that the environmental component of ARCD and ARD is well-established, [10][11][12][13][14] and should be an important part of any model for disease etiology or intervention. This includes evidence for significantly increased risk of dementia as well as worse cognitive function associated with reduced physical activity, 10,[15][16][17] poor sleep, 10,18,19 metabolic disease, 20,21 nutrient deficiencies, 14,22 hormonal insufficiency, 23 altered body composition, [24][25][26][27] and social isolation or poor social support.…”

“…We must therefore make it very clear that we believe that the environmental component of ARCD and ARD is well-established, [10][11][12][13][14] and should be an important part of any model for disease etiology or intervention. This includes evidence for significantly increased risk of dementia as well as worse cognitive function associated with reduced physical activity, 10,[15][16][17] poor sleep, 10,18,19 metabolic disease, 20,21 nutrient deficiencies, 14,22 hormonal insufficiency, 23 altered body composition, [24][25][26][27] and social isolation or poor social support. 28 Early evidence is also mounting to suggest that lifestyle and environmental modification has the potential to prevent or even reverse ARD, especially when initiated early in the disease process.…”