Five years after the height of the SARS-CoV-2 (COVID-19) pandemic, scientists are beginning to unveil the infection’s potential long-term effects on the brain. We now know that following an acute COVID-19 infection, between 10% and 35% of people suffer from lingering effects called long COVID. For some people, these effects can be mild and short-lived, but for others, there may be lasting issues that may trigger a chain reaction of cognitive impairment.Long COVID is a condition following an acute infection of COVID-19 with symptoms lasting a few weeks to several months. Its effects vary from person to person and there are more than 200 reported symptoms. Common symptoms include extreme fatigue, memory problems or “brain fog,” lightheadedness and smell or taste impairment. Along with these symptoms, scientists conjectured that other long COVID effects might impact older people differently.
To better understand the connection between long COVID, potential cognitive impairment and aging-related neurodegenerative diseases, the Alzheimer’s Association gathered top scientists around the globe to study the effects of long COVID on the brain. Successive studies from the network show 1) long COVID has long-term effects on the brain and 2) cognitive impairment following long COVID may be more severe in older adults.
In their most recent study, published January 2025 in Frontiers in Aging Neuroscience, the global team led by Gabriel A. de Erausquin, MD, PhD, MSc, Zachry Foundation Distinguished Professor of Neurology, Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases, The University of Texas Health Science Center at San Antonio (UT Health San Antonio), explored the effects of long COVID on cognitive impairment among more than 3,500 adults from eight countries.
“This study highlights the profound and lasting impact that COVID-19 can have on the brain, particularly in older adults. We found that age, severity of infection and loss of smell are key factors linked to cognitive impairment after acute infection. Understanding these connections helps us uncover how the virus may contribute to brain changes and guide efforts to address its long-term effects on global brain health,” said de Erausquin.
Earlier studies by de Erausquin found that following COVID-19 infection, neurodegenerative biomarkers and inflammation in the brain were elevated, even among people without a history of neurodegenerative disease. This suggests COVID-19 infection may damage the central nervous system directly or in conjunction with a dysregulated immune system. Brains of people that had COVID-19 show a decrease in volume in both the limbic and olfactory systems, showing a possible connection to cognitive impairment and loss of the sense of smell (anosmia).
The scientists found that older adults who experienced more severe acute COVID-19 infection and lost their sense of smell had more symptoms of cognitive impairment following the infection. A battery of assessments showed younger and middle-aged adults had mild problems with attention and focus, but older participants had a noticeable decline in memory, language and executive functioning. Individuals who had more severe COVID-19 infection, were over 60 years old at the time of infection and experienced severe loss of smell had more pronounced cognitive impairment. Overall, older adults in the study had double the risk of moderate to severe dementia-like impairment following COVID-19 infection compared to younger adults.
Early in the COVID-19 pandemic, loss of smell and taste was a distinctive symptom of the infection. Likewise, an early dementia symptom is loss or change in smell and taste. It is well-established that memory and smell are connected and the pathway connection the two functions could be damaged during COVID-19 infection. Previous studies suggest that COVID-19 enters the brain through the olfactory system and causes inflammation and other symptoms that could lead to damage and possibly trigger neurodegenerative progression.
“Our findings emphasize the need to prioritize brain health in the aftermath of the COVID-19 pandemic,” said de Erausquin. “Understanding how the virus affects the brain will not only help us care for those with long COVID but also pave the way for advancements in prevention and treatment of neurodegenerative conditions.”
Related studies from de Erasquin and the International SARS-CoV-2 Network
Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer’s Association Global Consortium, (2022)Alzheimer’s & Dementia—Translational Research and Clinical Interventions.
The chronic neuropsychiatric sequelae of COVID‐19: The need for a prospective study of viral impact on brain functioning (2021) Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.