MPN’s and Alzheimer’s: Is there a connection?

by David Wallace and Lou Ann Donovan

Chronic inflammation is increasingly understood as a significant factor in the progression of many diseases, including Alzheimer’s and myeloproliferative neoplasms (MPNs), a group of blood cancers[1][2]. Myeloid blood cells, which are overproduced in MPNs, have been associated with Alzheimer’s disease, suggesting a link between these conditions[3].

Emerging evidence suggests that chronic inflammation plays a pivotal role in the progression of both Alzheimer’s and MPNs[2][4]. Understanding this association could have significant therapeutic implications, including the use of interferon-alpha2 or hydroxyurea to reduce elevated cell counts[5], or targeting chronic inflammation with Jak1-2 inhibitors, like ruxolitinib, in the treatment of Alzheimer’s[6].

The article by MPN expert, Dr. Hans Hasselbalch “Myeloproliferative blood cancers as a human neuroinflammation model for development of Alzheimer’s disease: evidence and perspectives” provides the foundation to support this hypothesis, although future research is needed.

Recognizing Normal Brain Aging Versus Memory Loss

As we age, our brains change as much as our bodies do. However, it’s essential to distinguish between normal aging and the signs of more serious conditions like dementia or Alzheimer’s, a brain disease that results in a slow decline in memory, thinking, and reasoning skills[7].

Here are some key differences:

Normal brain aging:

• Occasional forgetfulness, such as names or appointments, but remembers them later

• Struggles with unfamiliar tasks

• Makes an occasional error when managing finances or household bills

Dementia:

• Difficulty completing familiar tasks

• Gets lost when driving to familiar places

• May repeat themselves, have trouble following or joining a conversation

Alzheimer’s:

• Personality and behavior changes, such as anger, wandering, or hallucinating

• Memory loss that disrupts daily life

• Confusion about dates, times, seasons, and the passage of time

5 Tips for Brain Health

1. Stay Active
   • Physical activity is crucial for overall health, including brain health[8]. Start with low-intensity exercises like walking, yoga, or dancing and gradually incorporate interval and aerobic training. Strength training, using weights or your body weight as resistance, can also be beneficial.
2. Keep Learning
   • Engaging in new learning experiences can strengthen your brain and enhance concentration[9]. Be a lifelong learner and explore something new – learn a foreign language, enroll in a painting class, or attend a cooking class with friends.
3. Relax
   • Your brain needs downtime. Take breaks from digital screens throughout the day and establish a relaxing pre-bedtime routine. Try drinking herbal tea, listening to soothing music, or wearing warm socks to help you fall asleep.
4. Nourish Your Body
   • A healthy diet is beneficial for both your heart and brain. Reduce sugar intake, increase omega-3 fatty acids in your diet, plan meals in advance, and stay hydrated. Even mild dehydration can impact energy levels and disrupt brain function.
5. Connect with Others
   • Good relationships can improve brain plasticity and preserve cognitive abilities. Engage in social activities and maintain strong relationships with friends and family.

Don’t underestimate the importance of good sleep. Chronic sleep deprivation can impair memory, sometimes to the extent of appearing like dementia. Adequate sleep can enhance brain function and improve learning and memory.

Remember, our everyday experiences and habits can influence our brain health more than our genetic predispositions. Take care of your brain health and overall wellness.

References

1. Heppner FL, Ransohoff RM, Becher B. “Immune attack: the role of inflammation in Alzheimer disease.” Nat Rev Neurosci. 2015;16(6):358-372. doi:10.1038/nrn3880. https://pubmed.ncbi.nlm.nih.gov/25991443/
2. Hasselbalch HC. “Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?” Blood. 2012;119(14):3219-3225. doi:10.1182/blood-2011-11-394775. https://pubmed.ncbi.nlm.nih.gov/22318201/
3. Merlini M, Rafalski VA, Rios Coronado PE, et al. “Fibrinogen Induces Microglia-Mediated Spine Elimination and Cognitive Impairment in an Alzheimer’s Disease Model.” Neuron. 2019;101(6):1099-1108.e6. doi:10.1016/j.neuron.2019.01.014. https://pubmed.ncbi.nlm.nih.gov/30737131/
4. Engelhardt B, Vajkoczy P, Weller RO. “The movers and shapers in immune privilege of the CNS.” Nat Immunol. 2017;18(2):123-131. doi:10.1038/ni.3666. https://www.nature.com/articles/ni.3666
5. Kiladjian JJ, Giraudier S, Cassinat B. “Interferon-alpha for the therapy of myeloproliferative neoplasms: targeting the malignant clone.” Leukemia. 2016;30(4):776-781. doi:10.1038/leu.2015.315. https://pubmed.ncbi.nlm.nih.gov/26601783/
6. Zhang S, Wang XJ, Tian LP, et al. “Therapeutic effects of STAT3 inhibition on experimental murine dry eye.” Int J Mol Med. 2018;41(1):43-52. doi:10.3892/ijmm.2017.3200. https://pubmed.ncbi.nlm.nih.gov/31503282/
7. Alzheimer’s Association. “2022 Alzheimer’s disease facts and figures.” Alzheimers Dement. 2022;18(3):535-559. doi:10.1002/alz.12471. https://www.alz.org/alzheimers-dementia/facts-figures
8. Northey JM, Cherbuin N, Pumpa KL, Smee DJ, Rattray B. “Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis.” Br J Sports Med. 2018;52(3):154-160. doi:10.1136/bjsports-2016-096587. https://bjsm.bmj.com/content/52/3/154
9. Park DC, Bischof GN. “The aging mind: neuroplasticity in response to cognitive training.” Dialogues Clin Neurosci. 2013;15(1):109-119. doi: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3622463/