Alzheimer’s Disease, Music Therapy and Sex Hormones: An Unexpected Solution

Alzheimer’s disease (AD) is all around us, with over 5 million individuals diagnosed across the United States. Interestingly, of these 5 million Americans, over 3.5 million of them are women, suggesting women are significantly more likely to suffer from AD than men.^1,2 While AD is best known for its impairment of memory, both short-term and long-term depending on the extent of the illness, a variety of other symptoms may accompany memory loss such as disorientation, confusion about time and place, changes in mood and behavior, and difficulties with speech, eating, and walking. These symptoms, collectively, lead to a significant loss in communication and personal identity.

Low levels of sex hormones plays a significant role in the onset of AD, and have led many scientists and doctors to propose Hormone Replacement Therapy (HRT) as a potential treatment for this disease.^4,5 While levels of sex hormones decrease with age, Alzheimer’s patients routinely possess especially low levels of both testosterone and estrogen. Women see an especially rapid, significant drop in sex hormone levels with menopause, which subsequently leads to their significantly increased risk for developing AD. Both estrogen and testosterone have been linked to cell proliferation and nerve protection, and estrogen has been shown to increase cholinergic activity.^4,5 Additionally, these hormones have been shown to suppress the effects of beta-amyloid, a series of peptides which are involved in plaque formation and the development of AD. Specifically, estrogen and testosterone prevent beta-amyloid accumulation by increasing the activity of beta-amyloid-degrading enzymes, and also protect against its neurotoxicity. Collectively, testosterone and estrogen improve cognitive function and delay the progression and effects of AD.⁴ Despite the clear importance of these two hormones, HRT has not been accepted as a treatment of AD due to inconsistent results and a series of serious side-effects, such as heart-attack, stroke, and an increased risk for breast cancer and prostatic cancer.⁴

Recently, an article was published in the International Journal of Alzheimer's Disease which links sex hormones with music therapy, and thus proposes music therapy as an alternative to hormone replacement therapy.⁴ Stimulatory therapies, such as music therapy, have been extremely useful in the management of AD for many individuals. I have personally witnessed the benefits music can have on the mood and cognition of someone diagnosed with AD, and it is widely accepted as an effective treatment both in neuroscientific blogs (BrainBlogger), and the AD support community (Alz.org Blog). While music therapy can have a wide variety of effects, scientific studies have shown that music therapy moderates problematic behavior, improves social involvement, promotes better cognition and awareness, increases brain plasticity, and reduces levels of stress, anxiety and depression.⁶

Figures taken from Fukui et al. 2012 (see reference 4).

Although the behavioral effects of music therapy are well-supported, our understanding of why and how this treatment works biologically has been extremely limited. Fukui et al. have investigated these biological causes by measuring levels of testosterone and estradiol in 6 female AD patients in a nursing home, before and after three different therapy conditions: therapist only, music only, and music + therapist. Note that estradiol is one of three hormones which are collectively known as estrogens. Music therapy proved to be the only treatment which resulted in a significant increase in both estrogen and testosterone, while music alone solely increased estrogen levels (Figures 1 & 2). ⁴ Additionally, caregivers noted that problematic behavior decreased for 24 hours after music therapy, supporting previous behavioral observations associated with AD and music therapy. These results suggest that music therapy could be used as a natural alternative to hormone replacement therapy, increasing hormone levels by engaging in an activity, as opposed to direct injection.

Of course, it should be noted that this study’s methodology is far from full-proof. With only six participants it can hardly be considered an all-inclusive study, and Fukui et al. make no mention of how much music therapy is needed before results are seen. Perhaps most importantly, the authors fail to include how severe each patient’s AD was, leading to questions about how effective this treatment will be at various stages of the disease. However, despite these experimental flaws, I hope that this study encourages other researchers to investigate music therapy as a natural alternative to hormone replacement therapy for Alzheimer’s disease. While these studies are difficult, research on larger populations with AD of varying severity as well as differences in exposure to music therapy are necessary for the implementation of this treatment on a larger scale. Music therapy would be a fantastic treatment in that it is low-cost, non-invasive, and perhaps even enjoyable for these patients who so badly deserve relief from their symptoms.

References:

1. Alzheimer's Association. (2014). 2014 Alzheimer's Disease Facts and Figures. Retrieved from: http://www.alz.org/downloads/facts_figures_2014.pdf
2. Bao A., Swaab D.F. (2011). Sexual differentiation of the human brain: relation to gender identity, sexual orientation and neuropsychiatric disorders. Front Neuroendocrinol, 32, 214-226.
3. Alzheimer's Association. (2014). What is Alzheimer’s? Retrieved from: http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp
4. Fukui H., Arai, A., Toyoshima, K. (2012). Efficacy of Music Therapy in Treatment for the Patients with Alzheimer’s Disease. Int J Alzheimers Dis, vol 2012.
5. Barron A.M., Pike, C.J. (2013) Sex hormones, aging, and Alzheimer’s disease. Front Biosci (Elite Ed), 4, 976-997.
6. Wollen, K. A. (2010). Alzheimer’s disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Altern Med Rev, 15(3), 223-44; Sakamoto, M., Ando, H., & Tsutou, A. (2013). Comparing the effects of different individualized music interventions for elderly individuals with severe dementia. International Psychogeriatrics, 25(5), 775-784; Koger, S. M., Chapin, K., & Brotons, M. (1999). Is music therapy an effective intervention for dementia? A meta-analytic review of literature. Journal of Music Therapy, 36, 2-15.