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Slow-Wave Sleep and Dementia: Pharmacological Interventions


David Rijckaert III: Old man sleeping, Circa 1640 - 1642

Sleep disorders, especially insomnia, increase with age and are often associated with cognitive decline. In older age, this tends to be associated with less restful sleep, specifically less slow-wave sleep (SWS) or Stages 3 and 4, which are the deepest sleep stages. This lack of SWS, as we know, is associated with Alzheimer's disease and the pathological consequences such as beta-amyloid (Amyloid beta, Aβ) accumulation. A fairly recent study (La et al., 2019) examined the long-term effectiveness of the antidepressant trazodone (antagonist of 5-HT2A and 5-HT2B receptors), often used for sleep because of its sedative properties, on potentially mediating this age-related decline in SWS, which might, theoretically, halt or even reverse AD pathology. The authors propose that trazodone, with long-term use, can increase SWS. In their study, they employed two groups of participants (age range: 74-83): (1) 25 participants who regularly use trazodone (median dosage 50 mg QHS), which include those with a diagnosis of AD, those with a notable yet mild cognitive impairment, and those without any impairment, and (2) 25 age-matched controls. The Mini-Mental State Examination (MMSE) was used to obtain a baseline level of cognitive abilities. Over the four years of the study, the age-matched control group, which were individuals not using trazodone, showed a significantly greater cognitive decline on the MMSE than trazodone users, including those with AD. The theory is that trazodone increases SWS and can halt the progression of age-related cognitive decline, even in those with AD. Of course, this study needs to be replicated with a larger group.


While waiting for larger replication studies, why not simply take this preventatively? Many life extension enthusiasts who employ preventative medical interventions would agree! Note: the therapeutic dosage used to induce sleep is, and for most in this study was, much lower than the therapeutic dosage used to treat depression.


References


  • La, A. L., Walsh, C. M., Neylan, T. C., Vossel, K. A., Yaffe, K., Krystal, A. D., Miller, B. L., & Karageorgiou, E. (2019). Long-term trazodone use and cognition: A potential therapeutic role for slow-wave sleep enhancers. Journal of Alzheimer’s Disease, 67(3), 911–921. https://doi.org/10.3233/jad-181145



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