Alzheimer’s disease is a neurodegenerative disease which currently affects over 55 million people worldwide, which is larger than the population of Canada. The majority of these patients are above the age of 65, and with the global lifespan moving far past that number, the risk of an individual developing Alzheimer’s disease is increasing dramatically. This paper aims to compare three different treatment methods, anti-amyloid (Donanemab), symptomatic (Donepezil), and physical activity on increasing quality of life measures on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale(ADAS-Cog) and Mini Mental State Examination (MMSE)  test among patients with early Alzheimer's above the age of 50.
 

Alzheimer's occurs due to two main factors, an accumulation of the amyloid-beta plaque, and neurofibrillary tangles caused by tau proteins in the microtubules of the neurons. The plaque aggregation occurs when Amyloid Precursor Protein (APP) is sliced by Beta-secretase, resulting in sAAP beta, which is then sliced again by Gamma Secretase, resulting in the protein Amyloid beta. Amyloid beta aggregates, resulting in the buildup of plaques between nerve cells, which reduces signal transmission between neurons. These plaques also trigger inflammatory immune responses in the body, resulting in cell death. This results in several patient symptoms, namely memory loss, cognitive decline, mood swings, and adverse social behaviour, which are what characterize Alzheimer’s Disease. Tau tangles, formed by the buildup of hyperphosphorylated tau protein, also contribute to the reduction of neuronal signal transmission, decreasing mental cognition. Tau is imperative to the microtubules that make up the cell membrane as these proteins prevent their dissociation, but when phosphorylated, it separates from the microtubules and becomes toxic in large amounts.  Several treatments are utilized to address the impacts of Alzheimer's disease, and they can be characterized into anti-amyloid, symptomatic, and physical therapy. The anti-amyloid treatment, specifically Donanemab, FDA approved in 2024, prevents the buildup of a certain type of amyloid beta known as Aβ(p3-42)  because it functions as a humanized monoclonal antibody that signals microglial cells for its removal. Donepezil was chosen to represent the symptomatic branch of Alzheimer’s  treatments. Donepezil addresses the symptoms of Alzheimer’s rather than the progression and root cause of the disease, those being the amyloid plaques and neurofibrillary tangles. It is further classified as an Acetylcholinesterase Inhibitor, which is a class of drugs that restrains the effects of Acetylcholinesterase. Acetylcholinesterase is an enzyme that breaks Acetylcholine, which has been shown to improve neuroplasticity and cognition. Although this treatment limits the effects of Dementia, it does not fully cure it. This specific medication was utilized for this paper due to its popularity and widespread usage among Alzheimer’s patients. Finally, physical therapy is a commonly suggested strategy to mitigate the effects of Dementia as physical activity has been correlated with delayed cognitive decline.  Currently, no paper compares all 3 of these types of treatments, meaning that the differences in effectiveness are very difficult to see. This paper aims to compare three distinct types of treatments in terms of how they can remedy the symptoms of Alzheimer’s Disease, the treatments being anti-amyloid, which targets the Amyloid beta plaques, symptomatic, purely targeting the symptoms, and physical therapy, related to physical and mental health, via a meta-analysis, a well reputed method of data comparison. This lack of comparison is a problem because it is very useful to see whether a specific treatment type can truly help a patient reduce Alzheimer’s risk, based on the research available. By writing a meta-analysis, medical professionals and patients alike have the ability to quickly see the results of drug trials to make the best decision on which treatment is best for them as an individual, without reviewing hundreds of papers all on the different treatments. The statistical analysis conducted is also very helpful for patients themselves, as many patients are primarily concerned with the symptoms of Dementia, rather than slowing progression, meaning a statistical analysis would allow them to make the best most relevant to their concerns. Furthermore, anti-amyloid treatments have been criticized for their tendency to produce negative side-effects such as nausea, headaches, and blood pressure variability (Mayo Clinic, 2024), which causes patients to weigh whether a significant difference in cognitive decline would be made between the three therapies be worth the risk of the side-effects.

 

Treatment Mechanisms:

Donanemab is an anti amyloid drug prescribed to those with early Alzheimer’s disease. Donanemab is further classified as a humanized monoclonal antibody (HMA), meaning that it is an antibody that was designed to mimic a human antibody as similarly as possible, usually derived from another animal’s antibody, in the case of Donanemab the animal was a mouse. HMA’s bind to an already existing, truncated version of amyloid beta, known as Aβ(p3-42), a form that is more prone to aggregation and accelerates the advancement of Alzheimer's disease. After binding to the truncated plaque, the antibodies then signal the microglial cells to clear the plaque from the brain via phagocytosis, partially clearing the brain of the plaque and therefore reducing the severity and progression of Alzheimer's disease (Hill-Mak, 2024). Donanemab has been known to induce side effects such as headaches, nausea, and blood pressure changes (Mayo Clinic Staff, 2024); However, due to its relatively recent FDA approval date, the symptoms of Donanemab are not well known yet.
Donepezil belongs to a class of drugs known as Acetylcholinesterase Inhibitors, which primarily aim to treat the symptoms. Acetylcholinesterase is an enzyme that allows for the breakdown of Acetylcholine, a neurotransmitter that is shown to be responsible for neuroplasticity and the creation of memories in humans. Acetylcholinesterase is normally released into the synapses of neurons, breaking Acetylcholine down via hydrolysis and resulting in its inability to function in the brain. Acetylcholinesterase inhibitors bind to Acetylcholinesterase’s active site, and subsequently remove its ability to catalyze the hydrolysis of Acetylcholine, allowing a higher concentration of Acetylcholine and therefore easier memory creation and retention. Donepezil is a reversible acetylcholinesterase inhibitor, meaning after some time, it dissociates from Acetylcholinesterase’s active site, allowing it to function normally, and then is promptly removed from the body as waste. Donepezil can be utilized to treat all stages of Alzheimer’s disease and may cause nausea, diarrhea, muscle cramps and fatigue.
Physical therapy encompasses a broad set of activities for patients, including but not limited to: aerobic and anaerobic exercise, assistance in performing physical activity for daily tasks, therapeutic exercise, etc. There has been a strong correlation observed between physical activity and cognitive improvement in areas such as memory retention, name recalling, and executive function although the exact correlation of the interaction between physical therapy and Alzheimer’s is not yet completely understood. Physical therapy has also been correlated with increased mental health and sociability.
Methodology
 

 

In order to efficiently search through the numerous clinical trials on all three treatments, set inclusion and exclusion criteria were applied. All included studies must have been published in English after 1995, have trials lasting longer than 6 weeks, and be freely accessible online in its full-text version from any veritable online database. The treatment must have not been used in combination, the patients must be above the age of 50, and the patient population must have been in either early stage or very probable Alzheimer’s Disease. All trials were selected to be randomized control experiments and must have included data regarding MMSE and ADAS-Cog scores of placebo and treatment groups. Furthermore, all trials had to have all events be independent of each other, a sample size greater than 30, random patient sampling, as they are prerequisites to the central limit theorem, allowing normality to be assumed and therefore the use of forest plots to capture the true mean for the population.
Primary Outcomes
For the purposes of this paper, “Quality of Life” was defined as the rate of cognitive decline, with a higher rate of  cognitive decline indicating lower quality of life and vice versa. In our research, we decided to compare both the Mini-Mental State Examination test (MMSE) and The Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) tests. This is because both tests are relatively easy to conduct, therefore allowing more researchers to collect data pertaining to it. Furthermore, they are both acclaimed by the scientific community for their accuracy of assessing change in cognitive ability. The MMSE is a 30 point test conducted to diagnose or to determine dementia and its severity in which a lower score indicates greater cognitive impairment. It evaluates multiple neurophysical aspects of Dementia, such as retention, language use, awareness etc. The test is praised  for its accuracy for being able to notice changes in severity of Dementia symptoms (Pezzotti, 2008). Additionally, the ADAS-Cog test is similar in nature to the MMSE test, but is more in depth in its diagnosis. Scores are given on a scale of 0-70, where a higher score denotes more cognitive impairment, and a lower score indicates lower cognitive impairment. This test has been described as appropriate for measuring the three treatments previously discussed (Kuiper, 2018), due to its thoroughness and ease of use, making it prominent in multiple studies, allowing for more data to analyze.
Data Filtering
All clinical trials were taken from Pubmed Clinical trials due to their reputability and ease of access. First, a scan of all papers that were found after inputting the search term(s) “Donepezil”, “Physical Therapy” and Donanemab (DO) followed by “Alzheimer’s” , along with the filter of being a randomized control trial, and being easily accessible, was conducted.  Afterwards, all papers would have their titles screened to ensure relevance to the topic. Subsequently, the abstract would be filtered to ensure that the study followed our inclusion and exclusion criteria. Then, trials would be scanned to see if they had the necessary data (ADAS-Cog and MMSE scores) published in order to conduct a statistical analysis. The remaining papers were then  screened to ensure they included the required data on the primary outcomes (MMSE and ADAS-Cog scores). Lastly, a quality screening occurred in which the remaining articles were thoroughly read through to ensure that they were not duplicates.
Data Extraction
All data was entered into a Google spreadsheet by name, year of publication, treatment type, outcome measures, methods, risk of bias, which was determined via analysing the conflict of interest statements and the funding for the trials, and ADAS-Cog and MMSE differences compared to placebo trials. Furthermore, one trial on Donepezil and one trial on physical therapy was split into two due to it as it compared different drug dosages.
Data Analysis
Due to the limitation of the data, it was determined that the best method of statistical comparison between the studies would be a mean difference between the treatment group and the placebo group, plotted on a scatterplot with a 95% confidence interval (CI). The purpose of this plot is to visualize the difference between the treatments compared to a placebo in order to determine the statistical trend that is seen and therefore which treatment is more efficient at alleviating the symptoms. All studies considered the following: treatment and placebo mean difference on Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Mini-Mental State Examination (MMSE). Excluded studies are noted on all plots when relevant.

Data Filtering

The initial search of Pubmed Clinical trials yielded  (D) = 36, (DO) = 6, (P) = 43, with (D) representing Donepezil, (DO) representing Donanemab, and (P) representing physical therapy. Afterwards, the title screening resulted in 55 trials (D) = 29, (DO) = 4, (P) = 23. Subsequently, abstract filtering occurred to make sure that the sample studied would fit within the inclusion and exclusion criteria (probable to moderate AD, above 50, male and female population), leaving 37 trials, (D) = 26, (DO) = 4, (P) = 7. Then, all trials dealing with drug combinations were removed, leaving 31 trials, (D) = 20, (DO) = 4, (P) = 7. Then, all trials that did not give the data specified or were not studying the correct outcomes were removed from the dataset, leaving 18 trials, (D) = 13, (DO) = 2 and (P) = 3. Lastly, a final filtering was conducted, removing all trials that were duplicates or had unsatisfactory methods leaving 8 trials, (D) = 3, (DO) = 2, (P) = 3. It should be noted that during the filtering process, two papers were each split into two different results, as they were studying different dosages. It should also be considered that the low number of trials concerning Donanemab is due to the fact that it was relatively recently made available, only being FDA-approved on July 2nd, 2024.

 

Figure 1. 

Screening Results. Note: n refers to total trials, D refers to Donepizel trials, DO represents donanemab trials and PT represents physical therapy.

 

 

Figure 2.
Difference in MMSE Results Compared to Placebo

Mini Mental State Examination (MMSE) 
Figure 2 is a forest plot displaying the mean difference between the treatments and the placebo groups. The confidence interval was either calculated by the formula CI = x ± 1.96  * sn, or the values given were used. Studies that were not included in the chart include: DO1, P3A , P3B and  P1 due to the fact that they did not provide the required data to perform the confidence interval calculations, however they did provide sufficient data for the ADAS-Cog test. The graph shows that Donepezil is consistent in its outcomes for the MMSE test, especially when compared to physical therapy. The data in the graph suggests that there is no significant difference between Donanemab and Donepezil with respect to improving MMSE score as all the error bars heavily overlap with each other, meaning that there is a high likelihood that the true means of the improvement in MMSE fall very close within one another.
Figure 3.
Improvement in ADAS-Cog scores compared to a placebo.

Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog)
Figure 3 is a forest plot comparing the mean difference between treatment and  placebo groups in ADAS-Cog improvement with a 95% Confidence interval. Similar to the previous graph, the CI was calculated by the following formula CI =  x ±1.96 *sn, or the data given were used. Trails that were not considered in the creation of the graph include: P2 and D3, as they did not provide the required information to calculate the mean difference and/or the confidence interval.  One physical therapy study was deemed an outlier due to its large error bars, meaning there is a large interval for the true mean, making the data point less valuable. The data provided suggests that physical therapy is significantly worse than Donanemab and Donepezil as their mean and error bars do not come particularly close to the error bars of the other studies. There also seems to be no significant difference between Donanemab and Donepezil, as their error bars overlap. 

In conclution, Donepezil and Donanemab are not significantly better or worse in terms of MMSE improvement, but physical therapy is significantly worse. Donepezil is slightly better than Donanemab and both have much better physical therapy at improving ADAS-COG scores. The data does not allow for a conclusive statement of the holistic improvement on quality of life.

To the best of the reviewers knowledge, this is the first comparison of Donepezil, Donanemab, and Physical therapy done, and on a wider note, the first between Anti-amyloid, symptomatic, and physical therapy for their effect in the rate of cognitive decline in Alzheimer's disease. The data in Figure 2 suggests that there is no statistically significant difference between Donamab and Donepezil in regards to improvement in MMSE scores, shown by the extreme overlap between both group’s confidence intervals. It seems that physical therapy performs significantly worse compared to Donanemab and Donepezil. Furthermore, one physical therapy trial seems to be an outlier, as it has a mean double the weakest donepezil study and error bars of approximately 2.5 points on both sides. It should be emphasized that all studies performed better than the control group, with some error bars indicating that they did worse, and that the results for all donepezil studies have little variation. In terms of ADAS-Cog scores, the data in figure 3 suggests that physical therapy seems to perform significantly worse, with two of the studies' means and error bars falling behind Donanemab. Donanemab seems to perform the same as Donepezil in terms of improvement of ADAS-Cog scores. It should be noted that the first Physical therapy study seems to be an outlier again, due to its large error bars, indicating great variation for the true mean difference. Overall, the data shows that there is no statistically significant difference between Donanemab and Donepezil in improving MMSE/ADAS-Cog scores, but they are both significantly better than physical therapy.  
One of the main limitations of this study is the lack of raw data that was available to analyze, this being for a few reasons. First, the relative recency of the drugs. Donanemab was FDA approved on July 2nd, 2024 and so does not have many trials conducted on it. This is juxtaposed with Donepezil, which was approved in 1996, and so has many more studies associated with it. Since there are so many total papers for all three treatments, it is very difficult for medical practitioners and their patients to find treatments that are right for them or fit their values. The lack of individual data can be corrected by waiting for more trials to come. However, simply increasing the number of trials available does not alleviate any of the previously raised concerns if the data they are provided are solely aggregated within treatments, rather than individual statistics. This would enable doctors to have more nuanced and statistically backed results and subsequent decisions. 
This paper could achieve wider and more conclusive results  by waiting for more trials that fit the inclusion/exclusion criteria to occur, and making sure they have better data to conduct statistical analysis with. For instance, data on individual MMSE scores would prove better than means, as it allows the review to see the spread, shape, outliers, and determine an accurate center, allowing for more tailored and statistically backed decisions to be made. Furthermore, by finding papers that deal with more tests for cognitive decline, such as the Integrated Alzheimer's Disease Rating Scale (iARDS), Montreal Cognitive Assessment (MoCA), and others, it is possible to make a more thorough judgement on the quality of each drug in relation to cognitive decline. A better comparison with the following measures and data would allow doctors to make more thorough decisions for their patients .
 

Refrences:

 Alzheimer's Disease International. (2021, September 21) ADI - Over 41 million cases of Dementia go undiagnosed across the globe – World Alzheimer Report reveals. Retrieved October 14, 2024, from [https://www.alzint.org/news-events/news/over-41-million-cases-of-Dementia-go-undiagnosed-across-the-globe-world-alzheimer-report-reveals/](https://www.alzint.org/news-events/news/over-41-million-cases-of-Dementia-go-undiagnosed-across-the-globe-world-alzheimer-report-reveals/)

 Alzheimer's disease and amyloid beta | Immune system and amyloid beta. (2021, June 22). YouTube. Retrieved October 14, 2024, from Alzheimer's disease and amyloid beta | Immune system and amyloid beta

 Alzheimer's Facts and Figures Report. (n.d.). Alzheimer's Association. Retrieved October 14, 2024, from [https://www.alz.org/alzheimers-Dementia/facts-figures](https://www.alz.org/alzheimers-Dementia/facts-figures)

 Alzforum.(2025, Jan 08). Kisunla. [Article]. Alzforum. Retrieved March 6th, 2025. From [https://www.alzforum.org/therapeutics/donanemab](https://www.alzforum.org/therapeutics/donanemab)

 APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer's. (2021, January 27). NCBI. Retrieved October 14, 2024, from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865856/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865856/)

 Avila, J., & Ochoa, S. (n.d.). The Importance of Tau Phosphorylation for Neurodegenerative Diseases. NCBI. Retrieved October 14, 2024, from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696910/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3696910/)

 Boada-Rovira, M. et al.(2004). Efficacy and Safety of Donepezil in Patients with Alzheimer’s Disease. [Article]. Sci Hub. Retrieved Month Date, Year, from [https://www.nejm.org/doi/10.1056/NEJMoa2100708?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed](https://www.nejm.org/doi/10.1056/NEJMoa2100708?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)

 Čolović, M. B., Krstić, D. Z., Lazarević-Pašti, T. D., Bondžić, A. M., Vasić, V. M.(2013, May 11). Acetylcholinesterase Inhibitors: Pharmacology and Toxicology. [Article]. PubMed Central. Retrieved March 6th, 2025 [https://pmc.ncbi.nlm.nih.gov/articles/PMC3648782/](https://pmc.ncbi.nlm.nih.gov/articles/PMC3648782/)

 Earlier Diagnosis. (n.d.). Alzheimer's Association. Retrieved October 14, 2024, from [https://www.alz.org/alzheimers-Dementia/research_progress/earlier-diagnosis](https://www.alz.org/alzheimers-Dementia/research_progress/earlier-diagnosis)

 Hill-Mak, J.(2024, May 30). Donanemab: Antibody Therapy Targeting Removal of Amyloid-β via Microglial Mediated Phagocytosis. [Article]. Mayo Clinic. Retrieved March 6th, 2025, from [https://jmsgr.tamhsc.edu/donanemab-antibody-therapy-targeting-removal-of-amyloid-%CE%B2-via-microglial-mediated-phagocytosis/](https://jmsgr.tamhsc.edu/donanemab-antibody-therapy-targeting-removal-of-amyloid-%CE%B2-via-microglial-mediated-phagocytosis/)

 How Is Alzheimer's Disease Treated? | National Institute on Aging. (2023, September 12). National Institute on Aging. Retrieved October 14, 2024, from [https://www.nia.nih.gov/health/alzheimers-treatment/how-alzheimers-disease-treated](https://www.nia.nih.gov/health/alzheimers-treatment/how-alzheimers-disease-treated)

 Kueper, J. K., Speechley, M., Montero-Odasso, M.(2018, Apr 24). The Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog): Modifications and Responsiveness in Pre-Dementia Populations. [Article]. PubMed Central. Retrieved March 6th, 2025 [https://pmc.ncbi.nlm.nih.gov/articles/PMC5929311/](https://pmc.ncbi.nlm.nih.gov/articles/PMC5929311/)

 Mayo Clinic staff.(2024, Jul 10). Alzheimer’s: Medicines Help Manage Symptoms and Slow Decline. [Article]. Mayo Clinic. Retrieved March 7, 2025 [https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048103#](https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048103#)

 Mendez, M. F. (n.d.). Early-onset Alzheimer Disease and Its Variants. NCBI. Retrieved October 14, 2024, from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538053/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538053/)

 Mintun, M. A. et al.(2021, Mar 13). Donanemab in Early Alzheimer’s Disease. [Article]. The New England Journal of Medicine. Retrieved Month Date, Year, from [https://www.nejm.org/doi/10.1056/NEJMoa2100708?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed](https://www.nejm.org/doi/10.1056/NEJMoa2100708?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed)

 Pezzotti, P., Scalmana, S., Mastromattei, A., Di Lallo, D.(2008, May 13). The accuracy of the MMSE in detecting cognitive impairment when administered by general practitioners: A prospective observational study. [Article]. PubMed Central. Retrieved March 6th, 2025, [https://pmc.ncbi.nlm.nih.gov/articles/PMC2426687/](https://pmc.ncbi.nlm.nih.gov/articles/PMC2426687/)

 Seltzer, B., et al.(2004, May 12). Efficacy of Donepezil in Early Stage Alzheimer Disease. [Article]. aaaaaaaJAMA Network. Retrieved March 6th, 2025 [https://jamanetwork.com/journals/jamaneurology/fullarticle/787258](https://jamanetwork.com/journals/jamaneurology/fullarticle/787258)

 Vsauce. (2016, July 2). Alzheimer's and the Brain. [Video]. YouTube. Retrieved October 14, 2024, from [https://www.youtube.com/watch?v=dWcdBOYy_bU](https://www.youtube.com/watch?v=dWcdBOYy_bU)

 What Is Alzheimer's Disease? | National Institute on Aging. (2021, July 8). National Institute on Aging. Retrieved October 14, 2024, from [https://www.nia.nih.gov/health/alzheimers-and-Dementia/what-alzheimers-disease](https://www.nia.nih.gov/health/alzheimers-and-Dementia/what-alzheimers-disease)

Bibliography:

A. Burns, M. Rossor, J. Hecker, S. Gauthier, H. Petit, H.-J. Möller, S.L. Rogers, L.T. Friedhoff; The Effects of Donepezil in Alzheimer’s Disease – Results from a Multinational Trial1. Dement Geriatr Cogn Disord 1 June 1999; 10 (3): 237–244. https://doi.org/10.1159/000017126

Boada-Rovira, M., Brodaty, H., Cras, P., Baloyannis, S., Emre, M., Zhang, R., & Bahra, R. (2004). Efficacy and Safety of Donepezil in Patients with Alzheimer Disease. Drugs & Aging, 21(1), 43–53. doi:10.2165/00002512-200421010-00004

Hoffmann K, Sobol NA, Frederiksen KS, et al. Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A Randomized Controlled Trial. Journal of Alzheimer’s Disease. 2016;50(2):443-453. doi:10.3233/JAD-150817

Jamat. (2004). Efficacy of donepezil in early-stage alzheimer disease: A randomized placebo-controlled trial | dementia and cognitive impairment | jama neurology | jama network. Jamat. https://jamanetwork.com/journals/jamaneurology/fullarticle/787258 

Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): randomised double-blind trial. (2004). The Lancet, 363(9427), 2105–2115. doi:10.1016/s0140-6736(04)16499-4

Nejm. New England Journal of Medicine. (2021). https://www.nejm.org/doi/10.1056/NEJMsb1901642?url_ver=Z39.88-2003 

Ornish D, Madison C, Kivipelto M, Kemp C, McCulloch CE, Galasko D, Artz J, Rentz D, Lin J, Norman K, Ornish A, Tranter S, DeLamarter N, Wingers N, Richling C, Kaddurah-Daouk R, Knight R, McDonald D, Patel L, Verdin E, E Tanzi R, Arnold SE. Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer's disease: a randomized, controlled clinical trial. Alzheimers Res Ther. 2024 Jun 7;16(1):122. doi: 10.1186/s13195-024-01482-z. PMID: 38849944; PMCID: PMC11157928.

 

Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R., & Friedhoff, L. T. (1998). A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology, 50(1), 136–145. doi:10.1212/wnl.50.1.136

 

This project would not have been possible in its current state without the help of the following people. First, Ms. Isha Goyal for her help in formatting, and advice for the paper. Additionally, Dr. Iaci Soares for keeping the review accountable and on track. Furthermore, Mx. Dallas for her help in editing the paper and catching mistakes. Mr. Merrick Fanning for his  advice and proof-reading on statistical analysis. Lastly, our friends for believing in us.