Rates of Alzheimer’s disease (AD) are rising worldwide, and research on the subject, particularly risk factors and correlation with cognitive impairment and decline are among the most important and applicable. Among those, data suggests that diet seems to be the most important risk factor to target.
For instance, is a very well-known fact that when Japan made the transition from the traditional Japanese diet towards the Western diet, AD rates rose 6% in about 20 years. But diet is also related to certain forms of diabetes, and Type-2 diabetes mellitus (T2DM) is widely recognized as an important risk factor for some forms of dementia. Research about the link between AD and T2DM have concluded that working memory and executive control, for instance, decline in the T2DM compared to healthy people. This decline is lesser in extent than those suffered by AD patients.
An even more important fact is that non-controlled T2DM is strongly related to Mild Cognitive Impairment (MCI) and AD worsening: a study found lower whole-brain volume in participants with both MCI and T2DM compared with participants who had MCI but not T2DM.
Similarly, measured neural activity in their frontal lobe (associated with higher mental functions and reasoning alongside with behaviour), sensory motor cortex (involved in the planning, control, and execution of voluntary movements), and striatum (mediates cognition involving motor function) measured as a function of glucose uptake in those areas, was lower in participants with both MCI and T2DM, than participants with MCI alone. All of this is evidence that T2DM may accelerate and worsen cognition deterioration in patients with AD by affecting glucose metabolism and brain volume.
So, glycemic control is highly encouraged for T2DM and may be beneficial for decreasing the incidence of AD and delaying its progression in diabetic patients.
Yet a third variable linked to both T2DM and AD, is Apolipoprotein E (APOE): among 94 T2DM-patients from the Framingham Heart Study Database, results demonstrated that AD was far more severe in T2DM-patients who were also APOE carriers.
The long-term impact of diabetes on the brain
The process that involves diabetes damaging the brain, leading to AD is well known: it involves pathological mechanisms including cerebral hypoperfusion and glucose hypometabolism. Both of them trigger inflammation and oxidative-nitrosative stress that in turn decrease nitric oxide and enhance amyloid-beta deposition, cerebral amyloid angiopathy, and blood-brain barrier disruption.
All of those changes are long lasting because they involve long-term damage of fatty acids, proteins, DNA, and mitochondria in neurons and glia. This, in turn, perpetuates energy metabolism dysfunction and amyloid-beta generation.
The end result is chronic cerebral hypoperfusion producing synaptic malfunction and neuronal degeneration, leading to both grey and white matter atrophy and AD. Other studies also observed increased glucose intolerance accompanied by the formation of advanced glycation end-products, and activation of the receptor for these end-products. These changes are thought to contribute to the processing of amyloid-beta precursor proteins and decreased amyloid-beta degradation.
One gene to cure them all?
On the other hand, one mechanism by which AD could influence and worsen diabetes was less known until recently. Physiological and molecular analyses demonstrated that centrally expressed human BACE-1 induced systemic glucose intolerance alongside a fatty liver phenotype, impaired hepatic glycogen storage, brain glucose hypometabolism, altered neuronal insulin-related signalling and increased forebrain and plasma lipid accumulation (i.e. triacylglycerols and phospholipids, mainly) in mice.
Even if this study is very recent and lacks some important details, it could demonstrate that there is one gene that regulates both glucose metabolism and amyloid production. This means that by targeting only one gene both diseases could be prevented or even stopped from progressing once any or both of them were diagnosed.
Dealing with AD and diabetes
Even if T2DM is a very important risk factor for AD, diet and a healthy lifestyle are also important to counter progression and onset of AD. Most of the recommendations that follow would decrease the risks of both T2DM and AD, if followed correctly and permanently over the long run.
Current research concerning diet for patients with high risk of AD draws no definitive dietary recommendations. However, high consumption of fats from fish, vegetable oils, non-starchy vegetables, low glycemic index fruits and a diet low in foods with added sugars and moderate (red) wine intake should be encouraged and seem to be one of the best patterns of consumption to prevent both diseases. This was the conclusion of a dietary research of 35 nutrients associated with cognitive function and AD.
Nutrient combinations were assessed using the Harvard/Willet Food Frequency Questionnaire. The identified most ‘AD-protective’ nutrient combination was mentioned above. And it came as no surprise as this combination is regarded as Mediterranean Diet and proved to be useful for preventing cardiovascular diseases and cognitive deterioration in almost every study performed on the subject.
However, diet can only slow down the onset of both T2DM and AD, no improvement of the already existing damage have been achieved through diet or any other mean. Controlling blood sugar is a great start for those who suffer AD and T2DM, but it can’t reverse the existing damage to the brain from AD or the damage of the peripheral tissues from T2DM.
Both for diabetes and Alzheimer’s disease, modern gene therapy shows promise and could achieve human genome manipulation in a decade or two leading to the cure of those conditions. Diabetes could be one of the first to be treated because it is a high-prevalence disease (about 6-8% of the entire world population have it, and increasing) and current research shows that a limited amount of genes are related to it.
Alzheimer’s disease could be a different story, as this is a multifactorial disease. Although, if involvement of BACE-1 is confirmed, both diseases could be treated by targeting one single gene. Curing T2DM and AD would be a great achievement for humanity, as both of them individually are among the most prevalent, disabling and costly chronic diseases of the 21st century.
References
Berti, V., Murray, J., Davies, M., Spector, N., Tsui, W., Li, Y., Williams, S., Pirraglia, E., Vallabhajosula, S., McHugh, P., Pupi, A., de Leon, M., & Mosconi, L. (2014). Nutrient patterns and brain biomarkers of Alzheimer’s disease in cognitively normal individuals The journal of nutrition, health & aging, 19 (4), 413-423 DOI: 10.1007/s12603-014-0534-0
Daulatzai, M. (2016). Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer’s disease Journal of Neuroscience Research DOI: 10.1002/jnr.23777
Grant, W. (2016). Using Multicountry Ecological and Observational Studies to Determine Dietary Risk Factors for Alzheimer’s Disease Journal of the American College of Nutrition, 35 (5), 476-489 DOI: 10.1080/07315724.2016.1161566
Guo, C., Zhang, S., Li, J., Ding, C., Yang, Z., Chai, R., Wang, X., & Wang, Z. (2016). Chronic hyperglycemia induced via the heterozygous knockout of Pdx1 worsens neuropathological lesion in an Alzheimer mouse model Scientific Reports, 6 DOI: 10.1038/srep29396
Li, W., Risacher, S., Huang, E., Saykin, A., & , . (2016). Type 2 diabetes mellitus is associated with brain atrophy and hypometabolism in the ADNI cohort Neurology DOI: 10.1212/WNL.0000000000002950
Matthews DC, Davies M, Murray J, Williams S, Tsui WH, Li Y, Andrews RD, Lukic A, McHugh P, Vallabhajosula S, de Leon MJ, & Mosconi L (2014). Physical Activity, Mediterranean Diet and Biomarkers-Assessed Risk of Alzheimer’s: A Multi-Modality Brain Imaging Study. Advances in molecular imaging, 4 (4), 43-57 PMID: 25599008
Perrone L, & Grant WB (2015). Observational and ecological studies of dietary advanced glycation end products in national diets and Alzheimer’s disease incidence and prevalence. Journal of Alzheimer’s disease : JAD, 45 (3), 965-79 PMID: 25633677
Pluci?ska, K., Dekeryte, R., Koss, D., Shearer, K., Mody, N., Whitfield, P., Doherty, M., Mingarelli, M., Welch, A., Riedel, G., Delibegovic, M., & Platt, B. (2016). Neuronal human BACE1 knockin induces systemic diabetes in mice Diabetologia, 59 (7), 1513-1523 DOI: 10.1007/s00125-016-3960-1
Redondo, M., Beltrán-Brotóns, J., Reales, J., & Ballesteros, S. (2016). Executive functions in patients with Alzheimer’s disease, type 2 diabetes mellitus patients and cognitively healthy older adults Experimental Gerontology, 83, 47-55 DOI: 10.1016/j.exger.2016.07.013
Solfrizzi, V., Panza, F., Frisardi, V., Seripa, D., Logroscino, G., Imbimbo, B., & Pilotto, A. (2014). Diet and Alzheimer’s disease risk factors or prevention: the current evidence Expert Review of Neurotherapeutics, 11 (5), 677-708 DOI: 10.1586/ern.11.56
Solfrizzi, V., Panza, F., Frisardi, V., Seripa, D., Logroscino, G., Imbimbo, B., & Pilotto, A. (2014). Diet and Alzheimer’s disease risk factors or prevention: the current evidence Expert Review of Neurotherapeutics, 11 (5), 677-708 DOI: 10.1586/ern.11.56
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