Reducing the Risk of Alzheimer’s Disease

Tube of testosterone gel

Project Summary

Testosterone and fish oil (DHA) are promising supplements to reduce the risk of developing memory problems and Alzheimer’s disease. A clinical trial is underway to evaluate their influence on men with memory complaints by measuring the development of amyloid plaque in the brain – a hallmark of Alzheimer’s.
  • Alzheimer’s disease and other dementias seriously compromise the welfare of over 46 million people worldwide.
  • Significant research effort has sought to understand Alzheimer’s disease, but we are currently without a treatment or adequate biomarkers to detect the early stage of the disease.
  • Reducing the chance of developing Alzheimer’s disease by addressing modifiable risk factors is a step that can be taken immediately, prior to having a cure.
  • Development of noninvasive or easily-obtainable biomarkers for early stages of dementia and Alzheimer’s disease would support widespread testing and likely better outcomes with earlier treatments.
  • Parsemus Foundation aims to evaluate already available treatments to reduce the risk of developing Alzheimer’s disease.
  • The foundation has supported the early stages of a clinical trial to better understand the impact of testosterone and DHA (fish oil) on cognition in men with memory complaints. The study also seeks to develop early diagnostic tests for Alzheimer’s disease.

Project Topics

Alzheimer’s disease

Alzheimer’s disease affects the brain’s neurons that carry messages to other parts of the body. It is characterized by the accumulation of the protein fragment beta-amyloid (amyloid plaques) outside neurons and the accumulation of an abnormal form of the protein tau (neurofibrillary tangles) inside neurons. The impact of the plaques and tangles results in a vicious cycle of inflammation and atrophy of the brain. At first the brain can compensate, and the disease process can go on for 20 years before clear cognitive and behavioral changes signal a problem. Memory loss, impaired judgment, confusion, depression, personality changes and loss of interest may then occur.

The prevalence of Alzheimer’s disease increases dramatically with age, with most people suffering from the disease being over the age of 65. Over 5 million people age 65 and over in the United States have the disease, and over 46 million people worldwide are living with dementia. More women than men develop Alzheimer’s disease, and certain genetic profiles have higher incidence of the disease. While we cannot do much to change our sex or genes, there are modifiable risk factors. Probably the most important is maintaining cardiovascular health, since the same risk factors for cardiovascular disease (obesity, high blood pressure, high cholesterol) are also associated with increased risk for dementia. Physical exercise and a heart-healthy diet are key components to reducing the risk of both heart disease and Alzheimer’s disease.

Evaluating the effects of testosterone and DHA on memory

Testosterone levels in both men and women decline with age, and low testosterone levels have been related to memory problems. Studies have shown that low testosterone levels have preceded cognitive impairment and the neuropathology of Alzheimer’s, indicating it may be more of a cause than a consequence of the disease. The relationship between testosterone replacement therapy in men and women has been harder to quantify due in part to the small number of long-term, controlled studies available.

Another factor critical to brain function is omega-3 fatty acids, including DHA and EPA which usually come from fish oil. In the brains of older people, there is a depletion of long chain omega-3 fatty acids, and those with Alzheimer’s disease have lower DHA levels. DHA supplements can reduce markers of inflammation, which may influence Alzheimer’s disease. In dietary intervention studies, supplementation with DHA and/or EPA seems to be more effective in improving cognition in early stages of cognitive impairment.

DHA molecule
Molecular structure of DHA. Photo credit: Karl Harrison 3DChem.com

To help better understand the influence of testosterone and DHA on memory, the Parsemus Foundation provided early support for a randomized controlled prospective trial on the impact of testosterone or DHA  versus placebo on the onset of amyloid plaque associated with Alzheimer’s disease in men with memory complaints. The study is being conducted at the McCusker Alzheimer’s Research Foundation in Western Australia. Based on the results of a smaller non-placebo trial, the researchers led by Dr. Ralph Martins are optimistic that one or both treatments may slow the development of amyloid plaque and cognitive decline.

The trial has been screening men by completing a positron emission tomography (PET) amyloid scan prior to selection for the trial. In addition to the treatment arms, blood tests and retinal images from all participants will help to develop early diagnostic tests for Alzheimer’s disease.

Take Action

Learn more about dementia and Alzheimer’s disease – and what you can do to lower your risk. See more information sources below.

If you are interested in supporting the clinical trial of testosterone, DHA and Alzheimer’s disease, contact info@parsemus.org. More funding is needed to complete the trial.

  • For general information, research trials, and prevention information regarding Alzheimer’s disease, see: Alzheimer’s Association, Alzheimer’s Research and Prevention Foundation, list of Alzheimer’s Research Centers and Organizations.

  • Asih PR, Tegg ML, Sohrabi H, Carruthers M, Gandy SE, Saad F, Verdile G, Ittner LM, Martins RN. (2017). Multiple mechanisms linking type 2 diabetes and Alzheimer’s disease: Testosterone as a modifier. J Alzheimers Dis. 59(2): 445–466. (Free full text).

  • Martins RN, Villemagne V, Sohrabi HR, et al. (2018). Alzheimer’s disease: A journey from amyloid peptides and oxidative stress, to biomarker technologies and disease prevention strategies-Gains from AIBL and DIAN cohort studies. J Alzheimers Dis. 62(3):965-992. (Free full text).

  • Thomas J, Thomas CJ, Radcliffe J, Itsiopoulos C. (2015). Omega-3 fatty acids in early prevention of inflammatory neurodegenerative disease: A focus on Alzheimer’s disease. Biomed Res Int. 2015:172801. (Free full text).

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