The most common cause of dementia, accounting for about 60% of all cases of dementia, is Alzheimer's disease (AD). AD is a debilitating and incurable brain disease that affects about six million Americans age 65 and older. Current pharmacological treatments are of little benefit and do little or nothing to slow the progression of the brain damage that leads to the continuing loss of additional cognitive function in patients with AD. Absent the discovery of successful pharmacological treatments that can effectively prevent or at least successfully slow the progression of the loss of functional brain cells, the number of cases of AD in the US alone is projected to reach nearly 14 million cases by 2050, due in large part to our aging population. AD is characterized by the build up of two toxic proteins (beta-amyloid and tau) in the brain that destroy its ability to function.One of the most promising strategies that likely can help prevent or at least delay the onset of AD is the adoption of a healthier diet and lifestyle. A good quick review of potential dietary factors and a review of ongoing research can be found here (1). Vascular Dementia Causes About 20% of Dementia CasesThe second most common cause of dementia is the US is vascular dementia (VD) or about 1/3 as common as AD. Cardiovascular disease (CVD) can lead to a series of small strokes that reduce cognitive function or can reduce blood flow to parts of the brain sufficiently to reduce brain function. People with CVD in middle age are more likely to develop both VD and AD. Hence, it appears that most of the risk factors for CVD, such as diabetes, hypertension, abnormal plasma cholesterol, high intake of saturated fat, thromboembolic episodes, high fibrinogen concentrations, high serum homocysteine, atrial fibrillation, smoking, alcoholism, atherosclerosis, and apolipoprotein E4 (ApoE4) allele, are risk factors for developing both AD and VD (2).It has been known for some time that CVD risk factors in mid-life predict an increased risk of developing AD years later (3). More recently a new study focused on risk factors that appear to lead to the more rapid declines of cognitive skills in middle age. “Cardiovascular risk factors, especially high blood pressure and diabetes, become more common in midlife. We found those two risk factors, as well as smoking, are associated with higher odds of having accelerated cognitive decline, even over just a short span of five years.” “In other words, people with these risk factors had a greater chance of having faster cognitive decline than a group of their peers who did not smoke or have high blood pressure or diabetes” noted study author Kristine Yaffe, M.D., of the University of California, San Francisco.  The results of Dr. Jaffe’s study suggest changing these risk factors in mid-life may help prevent the steepest declines in thinking and memory over time. The study involved 2,675 people with an average age of 50 who did not have dementia. Researchers measured their cardiovascular risk factors at the start of the study: 43% were considered obese, 31% had high blood pressure, 15% were smokers, 11% had diabetes, and 9% had high cholesterol. Participants were given thinking and memory tests at the beginning of the study and five years later. Then researchers estimated the association of the five CVD risk factors with decline in their performance on the thinking and memory tests was faster than was observed in a group of adults of similar ages. After adjusting for age, race, education, and other factors that could affect the risk of cognitive decline, Dr. Jaffe found that people who smoked were 65% more likely to have accelerated cognitive decline, those with HTN were 87% more likely to see cognitive decline, and those with diabetes were nearly 3X more likely to experience accelerated cognitive decline. A bit surprising was that obesity and high cholesterol levels were not significantly associated with cognitive decline. Other studies that have examined high cholesterol and dementia risk have had mixed results. In this study, subjects who had one or two of these CVD risk factors were nearly twice as likely to have accelerated decline in cognitive function than people with no risk factors. People with three or more of these CVD risk factors were nearly 3X as likely to have faster decline of thinking and memory skills as those with no risk factors. “Most public health prevention efforts focus on older adults, but our study suggests the need to look at cognitive performance across a person’s life span,” said Dr. Yaffe. The results of this study add to the evidence suggesting middle-aged adults with one or more CVD risk factors including smoking, HTN, and/or diabetes would likely benefit from adopting healthier diet and lifestyle (4).While Dr. Jaffe’s study did not find that high cholesterol was a risk factor for developing AD, other studies have found an association. Since there is no doubt elevated serum cholesterol and diets higher saturated fat and cholesterol promote more atherosclerosis, there is no question that elevated serum cholesterol is a risk factor for VD, so if the goal is to reduce dementia, it remains important to lower serum cholesterol levels with diet and often medications in middle-aged people to reduce their risk of developing dementia. New Blood Tests for AD May Help One of the challenges of studying the impact of diet and lifestyle changes on the progression of AD is the lack of an effective test that tells us who is developing AD. A new blood test has shown real promise in discriminating between persons with and without AD and, more importantly, in persons at known genetic risk it may be able to detect someone headed toward AD as early as 20 years before the onset of cognitive impairment appears, according to a large international study published  in the Journal of the American Medical Association (JAMA) (5).For many years, the diagnosis of AD has been based on the characterization of amyloid plaques and tau tangles in the brain, but accurate measurement can only be done after the AD patient dies. Finding a reliable biomarker to determine if a patient is likely developing the build-up of amyloid plaques and tau tangles that lead to AD would help researchers determine if diet and/or drugs can prevent or slow the development of AD. A reliable and inexpensive blood test would be of great help clinically and also greatly aid research into AD. This is the reason a new study looking at the biomarker phospho-tau217 (one of the tau proteins found in tangles) appears to provide a relatively sensitive and accurate indicator of both plaques and tangles that lead to AD in living subjects."The p-tau217 blood test has great promise in the diagnosis, early detection, and study of Alzheimer's," said Oskar Hansson, MD, PhD, Professor of Clinical Memory Research at Lund University, Sweden, who leads the Swedish BioFINDER Study and is senior author on the study who spearheaded the international collaborative effort. "While more work is needed to optimize the assay and test it in other people before it becomes available in the clinic, the blood test might become especially useful to improve the recognition, diagnosis, and care of people in the primary care setting." In the Swedish BioFINDER Study, the assay discriminated between persons with the clinical diagnoses of AD and other neurodegenerative diseases with 96% accuracy. This accuracy is similar to the far more expensive and riskier tau PET scans and measuring Cerbral Spinal Fluid biomarkers. It was better than several other blood tests and MRI measurements and it distinguished between those with and without an abnormal tau PET scan with an 93% accuracy. In each of these analyses, p-tau217 performed better than other blood test recently found to have some promise in the diagnosis of AD. Researchers have recently made some progress in the development of amyloid blood tests too, providing some valuable information about the other toxic protein believed to promote AD. While more work is needed before these tests are ready for use in the clinic, a p-tau217 blood test has the potential to provide information about both plaques and tangles, corresponding to the diagnosis of AD and showing real potential to advance the AD research and clinical care. "Blood tests like p-tau217 have the potential to revolutionize Alzheimer's research, treatment and prevention trials, and clinical care," said Eric Reiman, MD, Executive Director of Banner Alzheimer's Institute in Phoenix and a senior author of this study.Another blood test looking at micro-RNA in the blood also is showing some promise as an effective way of predicting if apparently healthy older adults may be heading for dementia or developing AD (6). Hopefully, researchers and clinicians will soon have cheaper and more efficacious way to predict and/or measure adverse changes occurring in the brain that are contributing to the development of dementia. Such tests will aid both researchers' and clinicians' efforts to help prevent or at least delay the onset of dementia via diet and lifestyle changes and/or the development of more effective drugs fr treating those at risk for or developing dementia.Bottom Line: The two most common causes of dementia (AD & VD) are likely promoted by a typical modern Western-style diet high in saturated fat, cholesterol, added salt, and refined carbohydrates and low in whole fruits, vegetables, legumes, and whole grains. Foods that are calorie-dense and highly-processed, along with beverage calories, promote weight gain, insulin resistance, type 2 diabetes, and increase the risk of dementia. Switching to a DASH-style or more Mediterranean-style diet composed largely of whole plant food with only a small amount of omega-3 rich seafood and perhaps some nonfat dairy or soymilk appears likely to slow the loss of cognitive function over time. New blood tests of biomarkers for dementia may allow us to fine-tune dietary advice and develop pharmacological agents that may help prevent much of the loss of brain function that all too often accompanies old age.  By James J. Kenney, PhD, FACNReferences:

1. https://www.nia.nih.gov/health/what-do-we-know-about-diet-and-prevention-alzheimers-disease.
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181710/
3. Whitmer RA, Sidney S, Selby J, Johnston SC, Yaffe K. Midlife cardiovascular risk factors and risk of dementia in late life. Neurology 2005;64:277-281.
4. https://n.neurology.org/content/neurology/early/2020/07/15/WNL.0000000000010078.full.pdf.
5. Palmqvist S, Janelidze S, Quiroz YT, et.al. Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA, 2020; DOI: 10.1001/jama.2020.12134.
6. https://www.sciencedirect.com/journal/neurobiology-of-aging/articles-in-press.