sleep, dementia, cardiovascular disease - brief notes

Journal articles:

Association of sleep duration in middle and old age with incidence of dementia (2021)
https://www.nature.com/articles/s41467-021-22354-2

- an epidemiological study followed people for 25 years and found those who reported sleeping 6 hours or less per night had 30% higher risk of dementia relative to those who reported sleeping at least 7 hours, on average

Sleep arousal burden is associated with long-term all-cause and cardiovascular mortality in 8001 community-dwelling older men and women (2021)
https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab151/6239256

- a polysomnography study found higher all-cause and cardiovascular disease associated with higher arousal burden (a measure of unconscious wakefulness) for women, associations were less strong for men; potential for arousal burden as a biomarker & modifiable risk factor

News articles:

Sleeping Too Little in Middle Age May Increase Dementia Risk, Study Finds (2021)
https://www.nytimes.com/2021/04/20/health/sleep-dementia-risk.html

- two researchers not involved in the Nature study indicated that it provides evidence of causation since the sleep changes were recorded earlier (25 years before symptoms) than it is thought that brain pathology changes such as plaque accumulation occur (around 15-20 years prior to onset of symptoms)


Middle-aged people who sleep six hours or less at greater risk of dementia, study finds (2021)
https://www.theguardian.com/society/2021/apr/20/middle-aged-people-who-sleep-six-hours-or-less-at-greater-risk-of-dementia-study-finds

- researcher quoted in this article notes that disrupted sleep is a prodromal symptom and not necessarily a cause

 

One explanation for the link between short sleep duration and dementia is that during sleep the glymphatic drainage system clears waste from the brain and lack of sleep results in reduced clearance and build-up of protein aggregates.

The Glymphatic System: A Beginner's Guide (2015)
https://pubmed.ncbi.nlm.nih.gov/25947369/

However, dysfunction of the locus coeruleus could result in sleep problems and as well as alterations in microvascular circulation. Changes in microvascular circulation have been  implicated in both pathogenesis of neurodegeneration and normal brain aging.

mTOR attenuation with rapamycin reverses neurovascular uncoupling and memory deficits in mice modeling Alzheimer's disease (2021)
https://pubmed.ncbi.nlm.nih.gov/33888602/

"Failure of the blood flow response to neuronal activation (neurovascular coupling, NVC) in a model of AD precedes the onset of AD-like cognitive symptoms and is driven, to a large extent, by mTOR-dependent inhibition of nitric oxide synthase activity. Our studies show that mTOR also drives AD-like failure of non-NO-mediated components of NVC, and importantly that it suppresses NVC in non-diseased animals. Thus, mTOR attenuation may serve to treat AD, where we find that nNOS is profoundly reduced early in disease progression, and potentially other neurological diseases of aging with cerebrovascular dysfunction as part of their etiology. Our studies also provide, to our knowledge, the first evidence for a role of mTOR in regulating NVC in non-diseased conditions in mice."

Unfortunately, the above article is paywalled and I have no means to access it. The following, however, is open-access, as are the other articles linked in this post:

mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging (2019)
https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acel.13057

 

The following review discusses the role of degeneration of the locus coeruleus in neuroinflammation and pathogenesis of dementia, Alzheimer's and Parkinson's:

Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia (2020)
https://pubmed.ncbi.nlm.nih.gov/33207731/

"Locus Coeruleus (LC) is the main noradrenergic nucleus of the central nervous system, and its neurons widely innervate the whole brain. LC is severely degenerated both in Alzheimer's disease (AD) and in Parkinson's disease (PD), years before the onset of clinical symptoms, through mechanisms that differ among the two disorders. 

...

New imaging and biochemical tools have recently been developed in humans to estimate in vivo the integrity of LC, the degree of neuroinflammation, and pathology AD/PD biomarkers; it is auspicable that these will allow in the near future to test the existence of a link between LC-neuroinflammation and neurodegeneration directly in patients." 

Comments

Post a Comment

Popular posts from this blog

Notes - week of 2020/10/26

 Learned about PON1 and PD yesterday by attending web conference presentation by Beate Ritz: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922777/ Anthocyanins increase PON1 and are thought to protective against PD, but they also increase NO production - hmm .... ~ Vitamin D levels are decreased in PD: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267215/ "After the discovery that the VDR and 1α-hydroxylase, the enzyme that converts vitamin D to its active form, were highly expressed in the substantia nigra, it was hypothesized that inadequate levels of circulating vitamin D may lead to dysfunction or cell death within the substantia nigra ( 25 , 26 )." Active vit D (calcitriol) is mainly produced in the kidneys, as is klotho. a-syn is produced in the kidneys throughout lifespan.  ~ Chronic kidney disease prevalence is lower in PD patients: https://www.mdsabstracts.org/abstract/prevalence-of-chronic-kidney-disease-in-patients-with-idiopathic-parkinsons-disease-in-a-tertia
Read more

mouse models of menopause / reproductive aging in social insects - brief notes

Image
    Another in a great series of webinars by NUS Medicine. 5:10 Start of 1st presentation - Berenice A. Benayoun - Why we need age-relevant mouse models of menopause Ovariectomized mice are not good models of menopause.  10:43 Slide - comparison of post-reproductive lifespan among mammalian species 18:46 VCD injection; VCD is 4-vinylcyclohexene diepoxide, an environmental toxicant that causes ovarian failure 20:31 Genetic models - Foxl2 +/- ; Fshr +/- 25:00 Start of 2nd presentation - Ingrid Fetter Pruneda - The molecular and cellular basis of high fertility in social insects Queen ants manage to have extremely high fertility at the same time as longer lifespan relative to worker ants. 35:20 ant reproductive mode can be flexible; some species have cyclic castes - switching from queen to worker and back 51:54 Apart from sex organs,  liver is most sexually dimorphic organ - important implications for drug metabolism { Does this have implications for liver transplantation? }
Read more

Aconitase

Image
Aconitase (aconitate hydratase) is a tricarboxylic acid cycle (TCA) enzyme that converts citrate to iso-citrate via cis-aconitate. It has an iron sulfur cluster that interacts directly with substrate and is prone to oxidation by superoxide. Inactivation of aconitase has been  implicated in neurodegenerative diseases [1]. A mutation in ACO2 is associated with Infantile Cerebellar-Retinal Degeneration [2]. from [2] : "The active (4Fe-4S) cluster was shown to be extremely sensitive to superoxide-mediated inactivation 10 and a decrease in AH activity was observed in several neurodegenerative diseases associated with the development of oxidative stress, in particular Friedreich ataxia [MIM 229300 ], Parkinson [MIM 168600 ], and Alzheimer disease [MIM 104300 ], 11 as well as in mice lacking mitochondrial superoxide dismutase. 12 The reduced AH activity in endomyocardial biopsies of individuals with Friedreich ataxia was attributed not only to oxidative stress but also to the im
Read more

geomagnetic fields, space, heart rate variability, autoimmune disease - brief notes

Two mind-blowing articles on the effects of geomagnetic field fluctuations on human health, published in highly ranked peer-reviewed journals. Otsuka et al. (2019) Anti-aging effects of long-term space missions, estimated by heart rate variability  https://www.nature.com/articles/s41598-019-45387-6 "Exposure to variable magnetic fields in space resulted in an increase in several HRV endpoints, suggesting that aging may also be slowed down in astronauts in space, as it was for Caenorhabditis elegans 18 . By contrast, our previous 1998–2000 studies (during solar cycle 23) in a subarctic area indicated that magnetic storms, which involved larger magnetic disturbances than those observed during ISS01 and ISS02, suppressed HRV indices in 19 clinically healthy subjects 24 . The decrease in HRV was statistically validated for TF (−18.6%, P = 0.00009), primarily contributed to by VLF (−21.9%, P < 0.000001) in conjunction with ULF (−15.5%, P = 0.00865) and LF (−14.2%, P = 0.001
Read more