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Dandona P, Mohamed I, Ghanim H, Sia CL, Dhindsa S, Dandona S, Makdissi A, Chaudhuri A. Insulin suppresses the expression of amyloid precursor protein, presenilins, and glycogen synthase kinase-3beta in peripheral blood mononuclear cells. J Clin Endocrinol Metab. 2011 Jun;96(6):1783-8. PubMed.
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Henan Academy of Innovations in Medical Science
This is a most interesting finding. One important observation after gastric bypass surgery is that the patients are almost immediately relieved from being diabetic. This is linked to increased GLP-1 release (see, e.g., Morínigo et al., 2006). It is not understood why the intestine suddenly releases a lot more GLP-1 after this surgery, but GLP-1 re-sensitizes insulin signaling.
Importantly, GLP-1 analogues also have neuroprotective properties and reduce amyloid synthesis, plaque load, and the inflammation response in animal models of AD. Nigel Greig's group from the NIH showed that the GLP-1 analogue exendin-4 has protective properties in a triple-Tg mouse model of AD (Li et al., 2010), and we showed that the GLP-1 analogue liraglutide has very clear protective properties in an APP/PS1 mouse model (McClean et al., 2011). Both drugs are already on the market as treatments for type 2 diabetes. This new study is an interesting confirmation of the idea that GLP-1 may be neuroprotective.
References:
Li Y, Duffy KB, Ottinger MA, Ray B, Bailey JA, Holloway HW, Tweedie D, Perry T, Mattson MP, Kapogiannis D, Sambamurti K, Lahiri DK, Greig NH. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease. J Alzheimers Dis. 2010;19(4):1205-19. PubMed.
McClean PL, Parthsarathy V, Faivre E, Hölscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. J Neurosci. 2011 Apr 27;31(17):6587-94. PubMed.
Morínigo R, Moizé V, Musri M, Lacy AM, Navarro S, Marín JL, Delgado S, Casamitjana R, Vidal J. Glucagon-like peptide-1, peptide YY, hunger, and satiety after gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2006 May;91(5):1735-40. PubMed.
The Chinese University of Hong Kong
It is very interesting and useful to understand that there may be a link between obesity and a higher risk of Alzheimer’s disease. Alzheimer's disease (AD) itself is a neurodegenerative disease which is characterized by progressive cognitive deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes (Bhat, 2010). It is also important to realize that, on the other hand, behavioral changes can be related to, or contribute to, the occurrence of AD.
Insight into correlated factors of AD can suggest and stimulate further research on the developmental and psychosocial issues that contribute to AD, e.g., lifestyle and social behaviors, emotion and stress, and also on potential preventive measures.
One innovative approach focuses on the relationship between post-traumatic stress disorder (PTSD) and AD. PTSD is common among veterans returning from combat or war. There is some evidence that PTSD may be associated with reduced cognitive function. However, no study has yet investigated if PTSD increases the risk of development of AD.
Kristine Yaffe at the University of California, San Francisco, and colleagues addressed this (Yaffe et al., 2009). They studied 181,093 veterans (aged 55 years and above without dementia) and 53,155 of them were diagnosed with PTSD. Mean age was 68.8 years and 97 percent were male. They followed the veterans from 2001 through 2007, tracking whether they were diagnosed with AD or dementia.
The researchers found that veterans with PTSD in the study developed new cases of dementia at a rate of 10.6 percent over the seven-year follow-up. Those without PTSD had a rate of 6.6 percent. Even after adjusting for demographics and medical and psychiatric comorbidities, people with PTSD in the study were still nearly twice as likely to develop AD or dementia compared to veterans without PTSD (HR = 1.8, 95 percent CI = 1.7-1.9). It is also interesting to find in the study that moderate alcohol consumption reduces the risk of AD.
Nevertheless, further research should be conducted to understand more about the links between anxiety, or related psychological factors, and occurrence of AD, in order to find ways to reduce the increased risk of dementia associated with these psychological morbidities.
References:
Yaffe K, Vittinghoff E, Lindquist K, Barnes D, Covinsky KE, Neylan T, Kluse M, Marmar M. Post-traumatic stress disorder and risk of dementia among U.S. veterans. . Alzheimers Dement. 2009 Jul;5 (4):P104.
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