Elijah Mak, Ph.D.

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SUMMARY

Elijah Mak, Ph.D., focuses his research on the early detection and progression of neurodegenerative diseases, particularly those within the dementia with Lewy bodies (DLB) spectrum. His work includes study of prodromal stages such as isolated REM sleep behavior disorder. He uses multimodal neuroimaging — such as structural and diffusion MRI — with PET imaging of amyloid, tau and neuroinflammation to investigate how multiple copathologies may influence brain changes and clinical outcomes. Dr. Mak also studies sex differences in the expression and impact of pathology to inform personalized staging and risk stratification in Lewy body diseases.

Focus areas

• Influence of multiple copathologies in DLB. Alzheimer's disease copathologies — particularly amyloid plaques and tau neurofibrillary tangles — are present in up to 80% of patients with DLB, making mixed pathology the rule rather than the exception. Despite this high prevalence, the mechanisms by which these Alzheimer's-related proteins affect brain structural integrity, accelerate neurodegeneration and influence clinical progression in DLB remain poorly understood. Dr. Mak investigates these interactions using multimodal neuroimaging, including diffusion MRI and PET imaging of amyloid, tau and neuroinflammation. Supported by a Department of Radiology Internal Grant and a Developmental Project Award from the Mayo Clinic Alzheimer's Disease Research Center, this work aims to clarify how these copathologies contribute to disease severity, neurobiological heterogeneity and therapeutic responsiveness in DLB.
• Early brain changes in prodromal DLB. Isolated REM sleep behavior disorder is recognized as one of the strongest clinical predictors of future development of DLB, yet the underlying brain changes during this prodromal phase remain elusive. Dr. Mak applies advanced diffusion MRI techniques, including neurite orientation dispersion and density imaging, to detect subtle alterations in white and grey matter microstructure before the onset of cognitive symptoms. This research — also supported by a Developmental Project Award from the Mayo Clinic Alzheimer's Disease Research Center — seeks to identify early imaging biomarkers that could enable risk stratification, predict conversion to overt neurodegenerative disease and inform biologically based staging models.
• Sex differences in in vivo biomarkers of DLB and Alzheimer's disease. Another key area of Dr. Mak's research involves examining whether biological sex modifies the effects of Alzheimer's disease and Lewy body pathologies on brain structure and function. He contributed neuroimaging expertise to the Kronos Early Estrogen Prevention Study Continuation, which evaluated the long-term effects of hormone therapy on white matter in postmenopausal women. His ongoing work is supported by a Women's Health Research Center Pilot Grant through Mayo Clinic’s Women's Health Research Center. Using multimodal neuroimaging, the study aims to uncover sex-specific patterns of vulnerability and progression in Lewy body and Alzheimer's disease, with the goal of informing more individualized diagnostic and therapeutic strategies.

Significance to patient care

Dr. Mak's research aims to better understand how changes in the brain caused by Alzheimer's disease might make symptoms worse in people with Lewy body dementia. This could help healthcare professionals determine whether treatments used for Alzheimer's also might help those with DLB. He also studies how brain diseases may affect men and women differently, which could lead to more-personalized care. Dr. Mak's goal is to help doctors diagnose these conditions earlier and provide better, more tailored treatment for patients and their families.

Professional highlights

• Rising Star Award (Silver), International Lewy Body Dementia Conference, 2022.
• Rising Star Award, Dementia Research Excellence and People Awards, Alzheimer's Society UK, 2018.
• IPA Junior Research Award in Psychogeriatrics (first prize), International Psychogeriatric Association, 2016.
• Gates Cambridge Scholarship, Gates Cambridge Trust, funded by the Bill and Melinda Gates Foundation, 2013.