Understanding the Path to Progression
Alzheimer’s disease (AD) is the 7th leading cause of death in adults in the United States.[1] The most frequent form of dementia, Alzheimer’s annihilates significant brain processes and memories. Scientists have investigated cognitive decline, an early symptom of this clinical condition, to better understand the disease’s path to progression. Despite copious amounts of research conducted on the subject, definitive cures have yet to be found to prevent the severe symptoms of Alzheimer’s disease and reduce the risk of cognitive decline.[2,3]
Common signs and symptoms of AD include memory loss, challenges in executive functioning skills (e.g., planning or solving problems) and difficulty completing familiar tasks. People with AD experience cognitive decline and are unable to function at their maximum mental capacity. This negative interference in behavioral and social skills affect people’s ability to live independently. In the diagnosis of AD, it is important to rule out potential mental health disorders, as many of the cognitive features of AD (particularly poor thinking ability and memory problems) are notably common symptoms of depression as well.[4]
Understanding the molecular aspects of Alzheimer’s is key to determining the causes of this disease. Molecular pathways of AD in the brain indicate a loss of blood flow due to certain plaques and show neuronal cell loss, affecting the development of AD.[5] The neurodegenerative properties of Alzheimer’s have shown to be associated with an accumulation of the amyloid-β protein, increased neuronal cell death, and reduced blood flow to the brain.[6] Scientists have attempted to illustrate the pathogenesis of AD with the widely known Amyloid cascade hypothesis, which describes the build-up of the β amyloid production as the cause of neurodegeneration and neuronal cell loss in AD.[7-10] This medical hypothesis illustrates that the deposition of amyloid protein corresponds to neurotoxicity, a critical element in Alzheimer’s disease.[11,12] These neurofibrillary tangles (masses of hyperphosphorylated tau protein in the brain) are a chief marker in detecting Alzheimer’s disease and are caused by the aggregation of amyloid plaques.[13,14]
The pathology of Alzheimer’s has been positively correlated with deficiencies in or elevated levels of: specific vitamins (particularly vitamin B); dietary folate; and levels of homocysteine.[15-17] Complex data sets by Farina et al. (2017), Mikkelsen et al. (2016), and Robinson et al., (2017), suggest elevated levels of homocysteine, an amino acid in the body, as a marker for Alzheimer’s disease.[18-20] Homocysteine is produced from the methylation cycle (a biochemical pathway involved in most chemical reactions that occur in the body); ineffective methylation reactions can lead to several health disorders, including neurological diseases such as Alzheimer’s.[21] Notably, a lack of vitamin B and folate causes a high level of homocysteine, which is believed to be a risk for cognitive decline.[22,23] Similar to homocysteine, Vitamin D deficiency has been shown to have an influence on AD due to its neurodegenerative accelerating property and causes a disturbance to the vascular system and endothelium.[24] Due to the effect of homocysteine on cognition and its link to contributing factors of AD (e.g., brain atrophy and oxidative stress) scientists are examining whether reducing its levels could restrict the progression of Alzheimer’s disease.[25]
Dietary modifications may reduce the risk of developing Alzheimer’s disease. De Wilde et al. (2017) and Robinson et al. (2017) have found that this neurological illness is common in the elderly population; as the majority of this cohort has low levels of vitamin B, folate, and vitamin D, supplementation may help ward off neurodegeneration, and ultimately, Alzheimer’s disease.[26,27] Research indicates specific dietary adjustments such as adhering to the Mediterranean diet (which is typically high in vitamin B and antioxidants) are recommended for protection against AD. Consisting primarily of plant-based foods and fish, the Mediterranean diet is low in unsaturated fats; conversely, diets high in fats have been linked to greater risk for AD. Further, de Wilde et al. (2017) have found direct correlations among obesity and diabetes with the development of Alzheimer’s.[28] Thus, current research suggests that changing one’s lifestyle, by supplementation of additional folate and other B vitamins (B6 or B12), may help lessen the probability of getting Alzheimer’s disease later in life. Keep in mind that it is important to consult a physician before adding any vitamins or supplements to ensure the dosage is appropriate for one’s specific needs as well as to safeguard against any adverse interactions with current medications or medical issues.
In addition to dietary adjustments, evidence suggests exercise has specific psychological benefits that pertain to AD. Meng et al. (2020) found that the risk of AD can be significantly lowered by 45%, to be exact, with physical activity.[29] For instance, doing exercise on a regular basis enhances neurogenesis, muscle development, memory improvement, and brain plasticity by improving the endurance of the brain towards oxidative stress and increasing energy metabolism, vascularization, and neurotrophin synthesis.[30] Through these mechanisms, exercise has positive effects on memory and cognitive functions. As for specific types of exercise, strength and resistance training in particular have been found to increase muscle mass which reduces the risk of individuals being diagnosed with AD.[31] Conversely, many studies have demonstrated that a lack of physical activity is one of the most common preventable risk factors for the onset of AD.[32] In addition, compared to medication, exercise has been shown to have fewer side effects and better adherence.
If you suspect you or someone in your family is exhibiting warning signs or symptoms of Alzheimer’s Disease, it is important to get tested as soon as possible as early detection is key to slowing the progression of this neurodegenerative disease. A qualified mental health professional such as a psychologist or psychiatrist can help rule out whether the symptoms stem from clinical depression or other cognitive-impairing disorders.
Contributed by: Preeti Kota
Editor: Jennifer (Ghahari) Smith, Ph.D.
REFERENCES
1 Centers for Disease Control and Prevention. (2022, January 13). FASTSTATS - leading causes of death. Centers for Disease Control and Prevention. Retrieved August 7, 2022, from https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
2 Mikkelsen, K., Stojanovska, L., Tangalakis, K., Bosevski, M., & Apostolopoulos, V. (2016). Cognitive decline: A vitamin B perspective. Maturitas, 93, 108–113. https://doi.org/10.1016/j.maturitas.2016.08.001
3 Mayo Foundation for Medical Education and Research. (2022, February 19). Alzheimer's disease. Mayo Clinic. Retrieved August 7, 2022, from https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/symptoms-causes/syc-20350447
4 Tsuno, N., & Homma, A. (2009). What is the association between depression and alzheimer’s disease? Expert Review of Neurotherapeutics, 9(11), 1667–1676. https://doi.org/10.1586/ern.09.106
5 Robinson, N., Grabowski, P., & Rehman, I. (2018). Alzheimer’s disease pathogenesis: Is there a role for folate? Mechanisms of Aging and Development, 174, 86–94. https://doi.org/10.1016/j.mad.2017.10.001
6 Ibid.
7 Ibid.
8 Roher, A. E., Kokjohn, T. A., Clarke, S. G., Sierks, M. R., Maarouf, C. L., Serrano, G. E., Sabbagh, M. S., & Beach, T. G. (2017). App/AΒ structural diversity and alzheimer's disease pathogenesis. Neurochemistry International, 110, 1–13. https://doi.org/10.1016/j.neuint.2017.08.007
9 Robertson, D. S. (2017). Proposed biochemistry of parkinson’s and alzheimer’s diseases. Medical Hypotheses, 109, 131–138. https://doi.org/10.1016/j.mehy.2017.08.013
10 Shao, W., Peng, D., & Wang, X. (2017). Genetics of alzheimer’s disease: From pathogenesis to clinical usage. Journal of Clinical Neuroscience, 45, 1–8. https://doi.org/10.1016/j.jocn.2017.06.074
11 Roher et al. (2017)
12 Robertson (2017)
13 Roher et al. (2017)
14 Ulstein, I., & Bøhmer, T. (2016). Normal vitamin levels and nutritional indices in alzheimer’s disease patients with mild cognitive impairment or dementia with normal body mass indexes. Journal of Alzheimer's Disease, 55(2), 717–725. https://doi.org/10.3233/jad-160393
15 Robinson et al. (2017)
16 Moretti, R., Caruso, P., Dal Ben, M., Conti, C., Gazzin, S., & Tiribelli, C. (2017). Vitamin D, homocysteine, and folate in subcortical vascular dementia and alzheimer dementia. Frontiers in Aging Neuroscience, 9. https://doi.org/10.3389/fnagi.2017.00169
17 Farina, N., Jernerén, F., Turner, C., Hart, K., & Tabet, N. (2017). Homocysteine concentrations in the cognitive progression of alzheimer's disease. Experimental Gerontology, 99, 146–150. https://doi.org/10.1016/j.exger.2017.10.008
18 Farina et al. (2017)
19 Mikkelsen et al. (2016)
20 Robinson et al. (2017)
21 Mikkelsen et al. (2016)
22 Ibid.
23 Farina et al. (2017)
24 Moretti et al. (2017)
25 Farina et al. (2017)
26 de Wilde, M. C., Vellas, B., Girault, E., Yavuz, A. C., & Sijben, J. W. (2017). Lower brain and blood nutrient status in alzheimer's disease: Results from Meta-Analyses. Alzheimer's & Dementia: Translational Research & Clinical Interventions, 3(3), 416–431. https://doi.org/10.1016/j.trci.2017.06.002
27 Robinson et al. (2017)
28 de Wilde et al. (2017)
29 Meng, Q., Lin, M.-S., & Tzeng, I.-S. (2020). Relationship between exercise and alzheimer’s disease: A narrative literature review. Frontiers in Neuroscience, 14. https://doi.org/10.3389/fnins.2020.00131
30 CHEN, W. E. I.-W. E. I., ZHANG, X. I. A., & HUANG, W. E. N.-J. U. A. N. (2016). Role of physical exercise in alzheimer's disease. Biomedical Reports, 4(4), 403–407. https://doi.org/10.3892/br.2016.607
31 Ibid.
32 Meng et al. (2020)