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By Meghan McCarthy 

Editor’s Note: This article is part of the Disability and Dementia Series, an ongoing project highlighting the experiences of individuals with intellectual disabilities who are affected by Alzheimer’s disease and related dementias (ADRDs). 

Why do some individuals develop Alzheimer’s disease and related dementias (ADRDs) while others do not?  

Cognitive resilience and resistance offer promising lens for understanding this complexity. This dual phenomenon is at the heart of ongoing research led by Rory Boyle, PhD, a postdoctoral research fellow at the Penn Frontotemporal Degeneration Center (FTD) Center. Along with an international team of colleagues, Dr. Boyle is working to develop a framework for understanding resilience and resistance in Alzheimer’s disease associated with Down syndrome (DSAD).  

Currently 1 in 9 people aged 65 and older in the general population is diagnosed with Alzheimer’s disease (AD). In comparison, it is estimated that over 50% of adults with Down syndrome (DS) are affected.  

This disparity is believed to be largely due to genetics. Individuals with DS have a third copy of the amyloid precursor protein (APP) gene, which increases their risk of amyloid buildup in the brain—a hallmark of Alzheimer’s disease (AD). 

However, some individuals with DS who show changes in their brain consistent with ADRDs—such as amyloid and tau accumulation—do not exhibit symptoms of dementia during their lifetime. Analyzing data from the brain bank at the University of California Irvine (UCI) Alzheimer’s Disease Research Center, Dr. Boyle and his team found that about 13% of cases examined did not present with dementia symptoms, despite neuropathological findings indicative of an AD diagnosis. 

This week, Dr. Boyle’s team published a manuscript providing a framework for future research on this discrepancy.  

A newly released book by investigative journalist Charles Piller has sparked concern across the Alzheimer’s research community — and not because of its critique of scientific misconduct. Rather, it’s the sweeping, unfounded suggestion that such misconduct permeates the field and undermines decades of rigorous progress in understanding and treating Alzheimer’s disease.

At the Penn Memory Center and beyond, researchers and clinicians are pushing back.

In a recent article for MedPage Today, Jason Karlawish, MD, co-director of the Penn Memory Center, cautions that Piller’s message in Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s, is sensational.

“The problem is that the facts don’t support Piller’s message,” Dr. Karlawish wrote. “It’s sensational, and in my experience, it’s causing harm.” He details how patients and research participants are becoming increasingly hesitant to engage in promising clinical trials or consider approved anti-amyloid therapies such as lecanemab (Leqembi) and donanemab (Kisunla).

The risks of such hesitation are real. “All of this undermines the successes we’ve made and the research we still have to do,” Dr. Karlawish wrote. While he acknowledged legitimate critiques of early decisions, such as the controversial approval of Aduhelm, he argues that the system, including peer review, government investigations, and public scientific discourse, worked to correct missteps and safeguard trust.

By Meghan McCarthy 

Malawi, a country approximately 7,826 miles from the Penn Memory Center (PMC), is celebrated for its vibrant culture, striking landscapes, and resilient people. Its diverse terrain is framed by majestic mountains with lively villages echoing with the sounds of children and rivers teeming with wildlife.  

Images from 2024 MLSFH Malawi

Despite its beauty, Malawi faces significant challenges. Ranked as one of the poorest countries in the world, over 50% of its population lives below the national poverty line. A prolonged drought in 2024 has further destabilized its agriculture-dependent economy, profoundly affecting the health and opportunities available to Malawians.  

For the past 25 years, the Malawi Longitudinal Study of Families and Health (MLSFH) has worked in partnership with local communities to understand the demographic, socioeconomic, and health conditions of this population. Initially focused on social networks and fertility, the study has since expanded to explore the social and contextual factors influencing health across the lifespan. 

Now, a team of Penn MLSFH researchers will test the validity of dried plasma spot (DPS) technology amongst Malawi communities to measure the prevalence of Alzheimer’s disease and related dementia (ADRDs) in this aging population.  

Author’s Note: This article is part of our coverage of the 2024 Alzheimer’s Association International Conference (AAIC). To view all highlights, please click here.   

At the 2024 Alzheimer’s Association’s International Conference (AAIC), hundreds of Alzheimer’s disease and related dementias (ADRDs) experts presented on innovative and diverse topics in the field. When reviewing poster presentations, the Penn Memory Center (PMC) Communication’s team noted that several researchers used speech analysis to measure cognitive decline. 

An everyday function, speech can be a critical marker for cognition. For instance, the pace at which someone speaks, complexity of words used, and pauses within speech are all qualities that can be analyzed.  

Among the many presentations, the work of Sanjana Skellikeri, PhD, and Galit Agmon, PhD, stood out for their innovative use of speech analysis to measure cognitive decline.   

Both women described their work in short summaries for PMC community members.  

By Meghan McCarthy 

I vividly remember the day Olivia (Liv) Hall became my best friend. We sat together on the bus ride home from a high school field trip, chatting about everything and nothing. Up until then, our friendship had grown through shared struggles in AP European History, staying after school for clubs, and taking photos at the annual Fall Ball. While I cherish those memories, they weren’t what truly bonded us. What brought us closer was something much deeper: our shared experiences as caregivers for our grandparents with dementia. 

Since that moment, Liv and I have been inseparable. We graduated high school together, attended Villanova University as roommates, and volunteered side by side. In our postgraduate era, we plan seasonal trips and connect daily over FaceTime.  

Looking back, Olivia went from being a dear friend to a best friend when she shared her caregiving story.  

Nearly ten years later, it’s a privilege to share it with the Penn Memory Center (PMC) community.  

By Meghan McCarthy 

What is one quality that makes you great?

For many, this question can be a difficult to answer. Traditional societal values often discourage openly complimenting oneself in public. Yet, Jean Haskell, facilitator of the Penn Memory Center’s Cognitive Comedy class, often begins sessions by posing this very question.

As I observed a fall class, I was struck by the ease and comfort with which participants responded.

“I try to be kind,” one participant said.
“I work out every other day,” another shared.
“I am great because of my wife,” a third added.

This seemingly simple question revealed a profound impact. It’s a question we might all benefit from asking more often. 

It has been yet another groundbreaking year for research in Alzheimer’s disease and related dementias (ADRDs). At the Penn Memory Center (PMC), we asked team members to reflect on the most impactful initiatives and publications from 2024.  

By Meghan McCarthy 

Author’s Note: This article is part of ongoing coverage of the 2024 Alzheimer’s Association International Conference (AAIC). To view all highlights, please click here. 

Recent research through the Departments of Bioengineering, Neurology, and Radiology at the University of Pennsylvania is exploring the biologic causes for atypical Alzheimer’s disease (AD). Led by Lasya Sreepada, MS, BS, a doctoral candidate at Penn’s School of Engineering and Applied Sciences, the team presented their work at the 2024 AAIC.

Atypical AD affects approximately 15 percent of AD patients. The term encompasses individuals who experience cognitive outcomes that differ from typical AD symptoms. For example, individuals with atypical AD may experience greater change in their behavior, personality, and language compared to symptoms predominantly based around memory. Usually, atypical AD patients also develop their symptoms at a younger age.

Atypical AD highlights the heterogeneity in Alzheimer’s disease and related dementias (ADRD), or the variance in disease symptoms and presentation.  

Sreepada’s work aims to understand ADRD heterogeneity. 

Lasya Sreepada