Makoto Ishii, MD, PhD

Makoto Ishii is a board-certified neurologist and an assistant professor of neuroscience at the Feil Family Brain and Mind Research Institute at the Joan and Sanford I. Weill Medical College of Cornell University. He studied chemical engineering as an undergraduate at Princeton University before completing the Medical Scientist Training Program at the Tri-Institutional MD-PhD Program (Weill Medical College of Cornell University/Rockefeller University/Memorial Sloan Kettering Cancer Center). In his PhD studies at Rockefeller University, Dr. Ishii studied novel pathways in the brain that regulate appetite and body weight.  After receiving his medical degree from Weill Cornell Medical College, he completed his residency training in neurology at New York Presbyterian Hospital - Weill Cornell Medical Center, where he also was chief resident.  Since finishing his clinical training, he has returned to the research laboratory to combine two of his main academic interests: Alzheimer’s disease and how the brain controls body weight.  His current research program involves investigating the complex interactions between body weight/adiposity and Alzheimer’s disease in the hopes of identifying novel pathways that may shed new light into this currently incurable and devastating disease.  Dr. Ishii is extremely grateful for the research support received from the BrightFocus Foundation and its generous supporters.

"A few years ago, my grandmother was diagnosed with Alzheimer’s disease (AD).  Prior to the disease onset, she was a strong loving woman who lived independently after my grandfather passed away.  She was very talkative and enjoyed having long conversations. When I visited, we talked about everything from her childhood growing up in downtown Tokyo, before the city was known as the electronics capital of the world, to how Japan and the rest of the world had transformed into a global city with cell phones and the Internet making it easier than ever to connect with one another.  Unfortunately, as the disease progressed, she began to require full time care and could no longer live on her own. Our conversations also started to change, as she started to lose track of time, sometimes slipping back to those early childhood years in a Tokyo that no longer exists. 

The most striking aspect of Alzheimer’s clearly is this loss of mental function that cruelly manifests as a simmering, relentlessly progressive dementia, resulting in a loss of identity and independence.  However, I see other manifestations.  I look at a photograph that I took of my grandmother a year before she was diagnosed and compare it to one taken only a couple years later.  My grandmother was never a thin woman, but within a few years of her diagnosis she had lost a significant amount of weight, despite eating what appeared to be her normal amount of food.  What causes this unintended weight loss?  Is it part of the disease?

Talking to my fellow clinicians and reviewing the literature, it is clear that weight loss and the associated metabolic deficits are a central part of the disease process.  Individuals who lose weight later in life appear to be at higher risk for developing AD, and once someone develops AD, weight loss strongly is associated with worsening disease progression and even increased risk of death.  Furthermore, this weight loss can occur early, before mental decline.  Despite overwhelming evidence that weight loss plays a prominent role, the exact significance and contribution of weight loss to the development of AD is not known. 

As a grandson, I feel at times helpless as my grandmother’s dementia continues to worsen.  As a clinician-scientist, I see the potential advances we can make by exploring clinical observations that can help solve the complexities of Alzheimer’s disease. The critical support from the BrightFocus Foundation and its generous donors will enable me to explore this avenue of research. It began as a very personal inquiry, but hopefully now will make a broader contribution to the large community of clinicians, research scientists, tireless family caregivers, and most importantly to the patients like my grandmother, who are all battling this devastating disease."