If one were to list the most common fears of people today, they would likely come up with a conglomerate including things like death, heights, spiders, and clowns. My biggest fear, however, is perhaps not so run-of-the-mill: dementia is something that’s all too common and all too detrimental to overlook as a serious life issue. Many young people probably don’t consider it a major concern in their lives – that it would happen years down the road and that it wasn’t really something they could control. Recent research, however, has drawn some surprising connections from dementia and Alzheimer’s to diabetes, particularly type II, which is mostly dependent on lifestyle. When they say that the decisions you make today affect you down the road, this is no exception.
Type II diabetes is characterized by high blood sugar caused by insulin resistance or insulin deficiency. It accounts for 90% of diabetes cases and correlates highly with obesity; both diseases have been growing tremendously in recent years. As serious a disease diabetes is already, there is evidence to show that it is a significant risk factor for developing Alzheimer’s later in life. The link between the two disorders seems to be insulin resistance. Cells resistant to insulin uptake don’t take in as much glucose either, leading to a deficit in energy. This makes the cell vulnerable to oxidation, which is a main cause of neurodegeneration. Another suggested pathway involving insulin resistance involves the dysregulation of lipid metabolism; improper disposal of lipids from brain cells promotes ceramide (a lipid class) accumulation, causing inflammation and toxicity as well as beta-amyloid accumulation, which leads to amyloid plaques and neurofibrillary tangles, resulting in neurodegeneration. Although the causes of type II diabetes include genetic factors, lifestyle is a main contributor, involving obesity, lack of physical activity, and poor diet.
Another risk factor greatly associated with Alzheimer’s development is a dysfunctionality of apolipoprotein E (ApoE). This is largely a genetic risk factor, but recently has been associated with vascular health. ApoE normally works against inflammation and plaque formation in the brain, but certain isoforms of the protein that translate to dysfunctional alleles of the gene. ApoE4 has been found to be the largest known genetic risk factor for developing Alzheimer’s disease; this isoform does not efficiently bind lipids for transport out of the brain, leading to inflammation and beta-amyloid accumulation as mentioned before. There is a mechanism involving vascular health, however, where ApoE4 does not control the inflammatory molecule cyclophilin A in the brain; the resulting increase in cyclophilin A activates the enzyme MMP-9, which causes damage to the blood brain barrier (BBB). Damaging the BBB can lead to many adverse effects, such as allowing neurotoxic chemicals that wouldn’t otherwise be able to cross the BBB into the brain, as well as increasing vulnerability to beta-amyloid deposit and accumulation. Although this is mostly a genetic risk factor via ApoE4, increasing vascular health can possibly counter the damage caused to the BBB, lessening the adverse effects of ApoE4 and lessening the risk for developing Alzheimer’s.
Although there are definitely genetic risk factors that play a significant role in the development of Alzheimer’s, the fact that there is growing evidence for lifestyle contributors should not be ignored. Lifestyle plays a huge role in the development of type II diabetes, which is now linked via insulin resistance to Alzheimer’s. The possible role of vascular health in maintaining the BBB and countering the damaging effects of ApoE4 is a fairly promising one as well, and hopefully there will be more research done to confirm this relationship. Losing the ability to think clearly for myself is one of my greatest fears in life. Taking into consideration these new studies, my lifestyle choices will definitely take a turn for the better. I hope others do the same.
A Frightening Proposition
