Lisa Mosconi, PhD
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Lisa Mosconi, PhD
 

Research Projects
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Alzheimer's and Women's Health: an Urgent Call

Two out of every three Alzheimer’s patients are women.

Even adjusting for lengthier lifetimes, women outnumber men 2:1 in the Alzheimer’s population. It is therefore urgent to acknowledge, investigate, and treat Alzheimer’s as a powerfully unrecognized and vital element in women’s health. At the Weill Cornell Women’s Brain Initiative, together with our colleagues at the University of Arizona, we have sought to answer the question that we didn’t hear many people asking. Why are women vulnerable?

We set out to shed light on this longstanding mystery by asking: what factors differentiate women from men, specifically as we reach middle age? The first and most obvious place to investigate was women’s fertility. Taking into account some diversity within, the biological systems and processes of fertility are common to all women. And equally ubiquitous across all women — in fact, one of the very hallmarks of women’s middle age — is the decline in fertility, and the beginning of menopause.

After rigorous study — and common knowledge to any woman in menopause — it turns out that from a biological perspective, menopause affects far more than fertility. When menopausal women experience various symptoms like hot flashes, night sweats, disturbed sleep, etc. they might not realize that these symptoms originate not in the ovaries, but in the brain. By using a brain imaging technique called positron emission tomography (PET), we demonstrated that the ebb in estrogen causes the loss of a key neuroprotective element in the female brain, with an aggressively higher vulnerability to brain aging and Alzheimer’s disease. Read the full story here.

Thanks to funding from the National Institute of Health/ National Institute on Aging (2P01AG026572, AG057931, 3P01AG026572-13S1), the Cure Alzheimer’s Fund, and Maria Shriver’s Women’s Alzheimer’s Movement, we are now in a unique position to unravel the molecular determinants of women's increased vulnerability to Alzheimer's -- and intervene.  Our published studies are here.

The PET scan to the left shows brain activity (e.g., metabolism) in a premenopausal woman; the scan to the right shows brain activity in a postmenopausal woman. The color scale reflects brain activity, with brighter colors indicating more activity, …

The PET scan to the left shows brain activity (e.g., metabolism) in a premenopausal woman; the scan to the right shows brain activity in a postmenopausal woman. The color scale reflects brain activity, with brighter colors indicating more activity, and darker colors indicating lower activity. The scan to the right (menopause) looks ‘greener’ and overall darker, which means that the woman’s brain has substantially lower brain activity (more than 30 percent less) than the one to the left (no signs of menopause). Our published studies are here [Mosconi et al Neurology 2017; PloS One 2017].

 
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Brain Health: More Diet than Destiny

Of all the organs in our body, the brain is the one most easily damaged by a poor diet. From its very architecture to its ability to perform, everything in the brain calls out for the proper food. In fact, the only way for the brain to receive nourishment is through our diet. Day after day, the foods we eat are broken down into nutrients, taken up into the bloodstream and carried to the brain to replenish depleted storage, activate cellular reactions, and finally, to be incorporated into our very brain tissue.

After rigorous study, it turns out that eating the wrong foods affects far more than our waistlines. When we eat a fatty, sugary meal and experience symptoms like sluggishness, brain fog, drowsiness -- what many of us don’t realize is that these symptoms originate not in the stomach but in the brain. The latest research, including my own work, indicates that a poor diet causes the loss of key structural and functional elements in the brain, with an aggressively higher vulnerability to brain aging and dementia. Our published studies are here.

This work is funded by National Institute of Health/ National Institute on Aging grants AG035137 and AG022374; funding from the Dept. of Neurology at Weill Cornell Medical College; and philanthropic support of the Alzheimer’s Prevention Clinic, Weill Cornell Memory Disorders Program.

Comparing brains on different diets: Mediterranean vs. Western Diet. To the left, you can see the MRI scan of a 52-year-old woman who’s been on a Mediterranean-style diet most of her life. Her brain takes up most of the space inside the skull (eg. t…

Comparing brains on different diets: Mediterranean vs. Western Diet. To the left, you can see the MRI scan of a 52-year-old woman who’s been on a Mediterranean-style diet most of her life. Her brain takes up most of the space inside the skull (eg. the white ribbon that surrounds the brain). The ventricles, those little butterfly-shaped fissures in the middle of the brain, are small and compact. The hippocampus (the memory center of the brain) is well-rounded and in close contact with the surrounding tissues. In comparison, the scan to the right shows the brain of a slightly younger, 50-year-old woman who’s been eating a Western-type diet for many years (e.g., fast foods, processed meat, dairy, refined sweets and sodas). The red arrows point to brain atrophy, or shrinkage, indicating neuronal loss. As the brain loses neurons, the space is replaced by fluids instead, which show up as black on an MRI. As the arrows indicate, there are more black areas present in the brain that has been fed a typical Western diet than in the brain that consumed a Mediterranean diet. These are all signs of accelerated aging and increased risk of dementia. Our published study is here [Mosconi et al JPAD 2015].

 
 

Weill Cornell Alzheimer's Prevention Clinic: the First of its Kind

Few discussions acknowledge that less than 1% of the population develops Alzheimer’s disease because of a rare genetic mutation in their DNA. For the remaining 99% of of the population, the real risk is not determined by our genes, but rather by the complex interplay of a multitude of factors including how we live our lives.

Recent groundbreaking population-based estimates showed that over one third of all Alzheimer’s cases might be preventable by leading a healthy lifestyle. At least 1 in every 3 Alzheimer's cases might be prevented by improving lifestyle choices in terms of diet, exercise, intellectual stimulation, and vascular risk reduction. Further, these interventions should be even more effective at achieving optimal cognitive fitness in every part of our lives.

The Alzheimer's Prevention Clinic (APC) at Weill Cornell Medical Center is the first Alzheimer's-prevention clinic in the United States. This specialized clinic focuses on cutting-edge prevention strategies and comprehensive education for the whole family. People interested in lowering their Alzheimer's risk are followed over time and receive a personalized plan based on many elements, such as risk factors, genes, medical conditions, and the latest scientific research. Patients are cared for using a sophisticated and interactive state-of-the-art research tool and database. This approach allows for ongoing monitoring and development of personalized therapeutic options aimed at reducing risk and providing optimal care. Our published studies are here.

This work is funded by National Institute of Health/ National Institute on Aging 2P01AG026572; funding from the Dept. of Neurology at Weill Cornell Medical College; and philanthropic support of the Alzheimer’s Prevention Clinic, Weill Cornell Memory Disorders Program.

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Family History of Alzheimer's disease: It's All About Your Mother

A family history of Alzheimer's disease significantly increases the risk for developing this disorder. We showed that which of your parents has the disease is very important. In fact, as further proof that female sex really matters, people whose mothers have (or had) Alzheimer's show increased risk of developing Alzheimer's themselves.

Alzheimer's is the most common form of dementia in late-life, affecting over 5 million elderly in the United States alone. In order to develop preventative treatments, it is necessary to identify those individuals who are at highest risk for developing Alzheimer's. People with a parent affected by Alzheimer's are at increased risk for developing the disease, but the biological and genetic mechanisms accounting for this increased risk are not known.

In a series of studies using biological markers of Alzheimer's, from brain imaging to cerebrospinal fluid proteins, we compared people with a maternal or paternal history of Alzheimer's, as well as those with both parents with Alzheimer's, to those with no family history. No matter which technique we used, only people whose mothers had Alzheimer's showed altered levels of Alzheimer's biomarkers, including reduced brain activity, increased brain atrophy, and increased accumulation of beta-amyloid protein (a major hallmark of Alzheimer's pathology), as well as proteins involved with oxidative stress (i.e., free radicals, which are harmful to the brain as well as the rest of the body). In contrast, individuals whose fathers had Alzheimer's and those with no family history had levels within normal range.

These data indicate that adult children of mothers with Alzheimer's may be at increased risk for developing the disease. It is therefore extremely important to understand the genetic mechanisms involved in maternal transmission of Alzheimer's disease, which are currently unknown. Identifying maternally-inherited susceptibility genes might lead to preventive treatments years before the onset of clinical symptoms. 

These studies led to several press releases and media interest world-wide. Our published studies are here.

These studies were supported by National Institute of Health/ National Institute on Aging grants R01 AG035137, AG022374, and grants from the Alzheimer’s Association.

Statistical parametric maps showing brain regions with progressive reductions in brain glucose metabolism in cognitively normal adults with a maternal history of Alzheimer's as compared to those with a paternal history (purple) and to those with no …

Statistical parametric maps showing brain regions with progressive reductions in brain glucose metabolism in cognitively normal adults with a maternal history of Alzheimer's as compared to those with a paternal history (purple) and to those with no family history (red). Progressively reduced metabolic activity in these same brain regions is indicative of increased risk of Alzheimer's. Our published studies are here.