Leuprolide Acetate: Attainable Remedy for Alzheimer’s Illness in Ladies

Alzheimer’s disease (AD) is one of the top ten causes of death in the United States. In 2014, approximately 5 million Americans had AD, a statistic that is projected to increase to 14 million by 2060

Patients with AD often have impaired cognitive and global function with symptoms such as memory loss, behavioral and personality changes, and other cognitive difficulties.2 As the number of cases continues to rise, doctors and patients alike ask themselves: What potential treatments may be effective? ?

A phase 2 study by Bowen et al. Leuprolide has been shown to slow functional and cognitive decline in a group of women with mild to moderate AD who are also receiving donepezil, an acetylcholinesterase inhibitor, 3,4

We have Dr. Interviewed Tracy Butler, MD, and an associate professor at Weill Medical College, Cornell University to learn more about leuprolide plus cholinesterase inhibition to reduce neurological decline in the Alzheimer’s study (LUCINDA) ( Identifier: NCT03649724), a 3-site, phase 2, randomized, double-blind, placebo-controlled study of treatment with leuprolide acetate in women with AD receiving a stable dose of donepezil. Study researchers are currently attempting to evaluate the effectiveness of a 48-week leuprolide regimen versus placebo on global and cognitive function, as well as biomarkers for neuron imaging

What are the relevant potential clinical implications of the results of this study?

Tracy Butler, MD: The LUCINDA study aims to reuse an existing drug – leuprolide acetate – to treat women with AD. Leuprolide is already approved for a number of indications, including prostate cancer and endometriosis in adults and precocious puberty in children. By repurposing an existing drug with a defined safety profile, we can build on extensive previous research and development efforts and reduce the time frame and cost of delivering a new AD therapy to patients.

Although the results of the study are not yet available, we hope that leuprolide plus donepezil will reduce or stop cognitive and functional decline in women with mild to moderate AD.

How did the current study build on the results of the previous phase 2 study (Bowen et al., 2015) on the use of leuprolide with cholinesterase inhibitors in patients with AD?

Dr. Butler: The previous study of leuprolide in women with AD (Bowen et al., 2015) only met its endpoints (preserved cognition and function) in the subgroup of [patients] who were also [receiving] Donepezil. Because this was a default subgroup analysis that included over 70% percent of [patients]Subgroup results must always be interpreted with caution. LUCINDA is designed to replicate and expand on these promising subgroup results by asking for all of this [patients receive] Donepezil and adding neuroimaging and blood biomarkers to clarify the mechanism of synergy between leuprolide and donepezil.

What has evidence using neuroimaging and plasma biomarkers to suggest about the mechanisms of action of leuprolide in AD?

Dr. Butler: While we don’t have any results from this study yet, we believe that one of the different mechanisms of action of leuprolide in AD may be to reduce inflammation. We therefore measure cytokines and [C-reactive protein] Blood levels.

The other main mechanism of action of leuprolide involves its ability to block luteinizing hormone (LH). In animal models of aging and AD, LH is a potent mitogen that initiates the abortive re-entry of postmitotic neurons into the cell cycle, resulting in amyloid production and deposition, tau phosphorylation, nuclear hypertrophy, and cell death.

Can you further discuss LH modulation of amyloid precursor processing in AD?

Dr. Butler: My colleague and co-[principal investigator]Dr. Craig Atwood of the University of Madison, Wisconsin, has shown in several animal studies that LH has no effect [amyloid precursor protein] (APP) production, however, alters APP processing towards the amyloidogenic pathway, suggesting that increased LH during menopause may contribute to it [amyloid beta] Filing. Leuprolide reduces LH, and this is believed to be its main mechanism of action in AD.

What limitations were found in this study?

Dr. Butler: Since we don’t have any results yet, it is difficult to identify limitations. The [coronavirus disease 2019] (COVID-19) The pandemic has postponed the start of the study and is a major barrier to inclusion in this and many other clinical trials in which the elderly are enrolled [participants]. We work hard to minimize the risk [of participant] COVID-19 exposure by different methods. We conduct study activities remotely when feasible, make key study visits as short as possible, do frequent deep cleans of the facility as per expert guidelines, and wear masks with clear panels for protection [participants] and employees without impaired communication, those with cognitive impairments [patients] may depend on facial visual features.

What further research is needed in this area?

Dr. Butler: LUCINDA accepts women with mild to moderate AD. If the study proves successful, we would like to expand this line of research to include presymptomatic [individuals] to see if cognitive decline can be prevented.

We would like to extend this study to men as well. The current study is limited in part to women because [gonadotropin-releasing hormone] Analogues like leuprolide have almost no negative effects in postmenopausal women, since sex hormone levels are already low. In contrast, leuprolide reduces testosterone in men, which is believed to be beneficial for exercise. Therefore, in men, we might consider testosterone add-back therapy along with leuprolide and donepezil.

Disclosure: Several authors of the study have stated that they are part of the pharmaceutical industry. See the original study for a full list of what the authors said.


1. Centers for Disease Control and Prevention. What is the burden of Alzheimer’s disease in the United States? Updated June 2, 2020. Accessed January 14, 2021.

2. National Institute on Aging. Alzheimer’s Disease Leaflet. Updated May 22, 2019. Accessed January 14, 2021.’s%20disease%20progresses%2C % 20people and% 20personality% 20and% 20behavior% 20changes.

3. Bowen RL, Perry G, Xiong C, Smith MA, Atwood CS. A clinical study on the Lupron Depot in the treatment of women with Alzheimer’s disease: preservation of cognitive function in patients who take an acetylcholinesterase inhibitor and are treated with high-dose Lupron for 48 weeks. J Alzheimers Dis. 2015; 44 (2): 549- 60. doi: 10.3233 / JAD-141626

4. US National Library of Medicine. The LUCINDA Study: LeUprolid Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer’s Disease (LUCINDA). Accessed January 14, 2020.

5. US National Library of Medicine. The LUCINDA Study: LeUprolid Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer’s Disease (LUCINDA). Accessed January 14, 2021.

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