Depression in Alzheimer’s Disease: An Alternative Role for Selective Serotonin Reuptake Inhibitors?

Elsworthy, Richard J; Aldred, Sarah

doi:10.3233/jad-180780

Cited by 42 publications

(27 citation statements)

References 129 publications

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“… 31 These findings suggest that depressive symptoms may be a prodrome of AD reflecting preclinical disease progression. 32 Evidence for associations of MDD and AD at the clinical and molecular levels also has been reported. 9 Reports have argued that oxidative stress leading to neuronal dysfunction could contribute to the development of both MDD and AD.…”

Section: Discussionmentioning

confidence: 95%

Sleep, major depressive disorder, and Alzheimer disease

et al. 2020

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ObjectiveTo explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer's disease (AD).MethodsWe conducted bi-directional 2-sample Mendelian randomisation analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (N = 446,118), the Psychiatric Genomics Consortium (N = 18,759), and the International Genomics of Alzheimer's Project (N = 63,926). We used the inverse variance weighted Mendelian randomisation method to estimate causal effects, and weighted median and MR-Egger for sensitivity analyses to test for pleiotropic effects.ResultsWe found that higher risk of AD was significantly associated with being a “morning person” (OR = 1.01, p = 0.001), shorter sleep duration (self-reported: β = −0.006, p = 1.9 × 10−4; accelerometer-based: β = −0.015, p = 6.9 × 10−5), less likely to report long sleep (β = −0.003, p = 7.3 × 10−7), earlier timing of the least active 5 hours (β = −0.024, p = 1.7 × 10−13), and a smaller number of sleep episodes (β = −0.025, p = 5.7 × 10−14) after adjusting for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR = 0.99, p = 7 × 10−13). However, we did not find evidence either that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD.ConclusionWe found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.

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Section: Discussionmentioning

confidence: 95%

Sleep, major depressive disorder, and Alzheimer disease

et al. 2020

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“…On top of this, the literature showed that RJ has the potential to improve general mental health of healthy volunteers [ 197 ]. It also documents antidepressant effects of RJ in animal models of depression and anxiety [ 201 , 212 ]. The cellular and molecular mechanisms underlying the action of RJ in animal models of AD and cognitive aging is not completely understood.…”

Section: Discussionmentioning

confidence: 99%

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Ali

2020

Antioxidants

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The astronomical increase of the world’s aged population is associated with the increased prevalence of neurodegenerative diseases, heightened disability, and extremely high costs of care. Alzheimer’s Disease (AD) is a widespread, age-related, multifactorial neurodegenerative disease that has enormous social and financial drawbacks worldwide. The unsatisfactory outcomes of available AD pharmacotherapy necessitate the search for alternative natural resources that can target various the underlying mechanisms of AD pathology and reduce disease occurrence and/or progression. Royal jelly (RJ) is the main food of bee queens; it contributes to their fertility, long lifespan, and memory performance. It represents a potent nutraceutical with various pharmacological properties, and has been used in a number of preclinical studies to target AD and age-related cognitive deterioration. To understand the mechanisms through which RJ affects cognitive performance both in natural aging and AD, we reviewed the literature, elaborating on the metabolic, molecular, and cellular mechanisms that mediate its anti-AD effects. Preclinical findings revealed that RJ acts as a multidomain cognitive enhancer that can restore cognitive performance in aged and AD models. It promotes brain cell survival and function by targeting multiple adversities in the neuronal microenvironment such as inflammation, oxidative stress, mitochondrial alterations, impaired proteostasis, amyloid-β toxicity, Ca excitotoxicity, and bioenergetic challenges. Human trials using RJ in AD are limited in quantity and quality. Here, the limitations of RJ-based treatment strategies are discussed, and directions for future studies examining the effect of RJ in cognitively impaired subjects are noted.

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“…Interestingly, patients categorized as the most severely agitated actually showed an increase in nighttime behavioral or sleep disruptions when treated with citalopram (Leonpacher et al, 2016). An intriguing body of work also suggests that early administration of SSRIs may also slow the progression of mild cognitive impairment to AD, perhaps through a mechanism by which serotonin affects the amyloid-β precursor protein, thereby reducing the accumulation of amyloid-β (Elsworthy and Aldred, 2019). It is also possible that serotonin's modulation of the circadian system could indirectly play a role in slowing or expediting this progression, as chronic circadian dysfunction exacerbates AD pathology (Musiek, 2015).…”

Section: Serotonergic Inputs To the Circadian Systemmentioning

confidence: 99%

Potential Pathways for Circadian Dysfunction and Sundowning-Related Behavioral Aggression in Alzheimer’s Disease and Related Dementias

Todd

2020

Front. Neurosci.

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Patients with Alzheimer's disease (AD) and related dementias are commonly reported to exhibit aggressive behavior and other emotional behavioral disturbances, which create a tremendous caretaker burden. There has been an abundance of work highlighting the importance of circadian function on mood and emotional behavioral regulation, and recent evidence demonstrates that a specific hypothalamic pathway links the circadian system to neurons that modulate aggressive behavior, regulating the propensity for aggression across the day. Such shared circuitry may have important ramifications for clarifying the complex interactions underlying "sundowning syndrome," a poorly understood (and even controversial) clinical phenomenon in AD and dementia patients that is characterized by agitation, aggression, and delirium during the late afternoon and early evening hours. The goal of this review is to highlight the potential output and input pathways of the circadian system that may underlie circadian dysfunction and behavioral aggression associated with sundowning syndrome, and to discuss possible ways these pathways might inform specific interventions for treatment. Moreover, the apparent bidirectional relationship between chronic disruptions of circadian and sleepwake regulation and the pathology and symptoms of AD suggest that understanding the role of these circuits in such neurobehavioral pathologies could lead to better diagnostic or even preventive measures.

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Depression in Alzheimer’s Disease: An Alternative Role for Selective Serotonin Reuptake Inhibitors?

Cited by 42 publications

References 129 publications

Sleep, major depressive disorder, and Alzheimer disease

Sleep, major depressive disorder, and Alzheimer disease

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

Potential Pathways for Circadian Dysfunction and Sundowning-Related Behavioral Aggression in Alzheimer’s Disease and Related Dementias

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