Hemaila Tariq ( Aga Khan University, Karachi )
Bilal Ahmed ( Department of Psychiatry, Aga Khan University, Karachi, Pakistan. )
Muhammad Yusuf Hafiz ( Department of Psychiatry, Aga Khan University, Karachi, Pakistan. )
Madam, Alzheimer's Disease (AD) is a complex neurodegenerative disease with a progressive degeneration of behavioural and cognitive functions such as memory.1 Alzheimer's disease is characterized by amyloid-b plaques, tau protein hyperphosphorylation, microglial cell activation and release of inflammatory cytokines such as IL-1b leading to disease progression. Amyloid-b plaques act on Toll-like receptors on microglial cells, thereby activating them and causing the release of pro-inflammatory cytokines.2 Milrinone is a Phosphodiesterase inhibitor that has vasodilatory effects in the vasculature and has shown to suppress neurocytes apoptosis and inflammation.3
A study performed on APP/PSI transgenic mice demonstrated that milrinone reduces formation of amyloid-b plaques, suppresses tau protein hyperphosphorylation and release of inflammatory cytokines and reduces neuroinflammation therefore improving memory and cognitive functioning and helps reduce the progression of Alzheimer's disease.4
As per recent statistics, low-middle income countries constitute 58% of the world's aging population and this is expected to reach 68% by 2050. China, South Asian countries including Pakistan and Western pacific neighbours have reported the fastest growth in their geriatric population.5 In Pakistan, a country of approximately 220 million people with an increasing elderly population, there are very limited dementia trained specialists and available treatment options.6 Milrinone, a drug conventionally being used in cardiovascular treatments, could help bridge this gap and allow us to cater to the increasing burden of Alzheimer's disease in Pakistan.
Conflict of Interest: None.
Funding Sources: None.
1. Kuar A, Sidhu J, Goyal A, Tsao JW. Alzheimer disease. [Online] [Cited 2021 August 11]. Available from: URL: https://europepmc.org/article/NBK/nbk499922
2. Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer's disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019; 14:5541-54.
3. Arac D, Erdi MF, Keskin F, Kenan M, Cuce G, Aydemir FH, et al. Neuroprotective effects of milrinone on experimental acute spinal cord injury: Rat model. World Neurosurg. 2021; 147:e225-33.
4. Chen Q, Yin Y, Li L, Zhang Y, He W, Shi Y. Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer's Disease in an APP/PS1 Mouse Model. Neuropsychiatric Disease and Treatment. Neuropsychiatr Dis Treat. 2021; 17:2129-39.
5. Alzheimer's disease International. Alzheimer's Pakistan launch report on Dementia in Humanitarian Settings. [Online] [Cited 2019 December 18]. Available from: URL: https://www.alz.co.uk/news/adi-gadaa-and-alzheimers-pakistanlaunch- report-on-dementia-in-humanitarian-settings
6. Population, total - Pakistan. [Online] [Cited 2019 November 12]. Available from URL: https://data.worldbank.org/indicator/ SP.POP.TOTL?locations=PK