SAN FRANCISCO — Alzheimer’s disease, the most common form of dementia, is synonymous with a number of awful, debilitating symptoms such as long-term memory loss, forgetfulness, disorientation, and, eventually, the inability to function independently on a day-to-day basis. Now, new research is calling attention to an overlooked early set of dementia symptoms called posterior cortical atrophy, or PCA.
PCA is a baffling collection of visuospatial symptoms that usually appear as the first symptoms of Alzheimer’s disease. After conducting the first-ever large-scale study focusing on PCA, scientists at UC San Francisco say PCA symptoms occur in up to 10 percent of Alzheimer’s disease cases.
This study features data encompassing over 1,000 patients at 36 sites across 16 countries. Simply put, researchers say their findings indicate posterior cortical atrophy (PCA) overwhelmingly predicts Alzheimer’s. As many as 94 percent of PCA patients displayed Alzheimer’s pathology, while the other six percent had conditions like Lewy body disease and frontotemporal lobar degeneration. Conversely, other studies have found that 70 percent of people with memory loss have Alzheimer’s pathology.
Dissimilar to memory problems, patients living with PCA have issues including:
- Judging distances
- Distinguishing between moving and stationary objects
- Completing activities like writing or picking up an item that has fallen to the floor
Curiously, despite these visual issues, most people with PCA can still pass a normal eye exam, explains Marianne Chapleau, Ph.D., of the UCSF Department of Neurology, the Memory and Aging Center, and the Weill Institute for Neurosciences. The majority of PCA patients displayed normal cognition to start, but by the time they had their first diagnostic visit (an average 3.8 years after symptom onset), mild or moderate dementia was apparent, with deficits detected across memory, executive function, behavior, and speech/language.
At the time of the diagnoses, 61 percent demonstrated “constructional dyspraxia,” or an inability to copy or construct basic diagrams or figures; 49 percent had “space perception deficit,” or difficulties identifying the location of something seen, and 48 percent had “simultanagnosia,” an inability to visually perceive more than one object at a time. Another 47 percent dealt with new challenges regarding basic math calculations, and 43 percent reported reading problems.
“We need more awareness of PCA so that it can be flagged by clinicians,” says Chapleau in a university release. “Most patients see their optometrist when they start experiencing visual symptoms and may be referred to an ophthalmologist who may also fail to recognize PCA. We need better tools in clinical settings to identify these patients early on and get them treatment.”
The average age of PCA symptom onset is 59 years-old. Notably, that’s several years younger than the average age of a typical Alzheimer’s diagnosis. This is yet another factor that contributes to PCA patients’ lower chances of diagnosis.
Study co-first author Renaud La Joie, Ph.D., also of the UCSF Department of Neurology and the Memory and Aging Center stresses that early identification of PCA may have important implications for Alzheimer’s treatment. During this project, amyloid and tau levels, found in cerebrospinal fluid and via imaging, in addition to autopsy data, ended up matching up with those found in usual Alzheimer’s cases. Consequently, patients with PCA may be candidates for anti-amyloid therapies, such as lecanemab (Leqembi), approved by the U.S. Food and Drug Administration in January 2023, as well as anti-tau therapies, which are currently in clinical trials. Both approaches should offer greater effectiveness during the earliest phases of the disease.
“Patients with PCA have more tau pathology in the posterior parts of the brain, involved in the processing of visuospatial information, compared to those with other presentations of Alzheimer’s. This might make them better suited to anti-tau therapies,” La Joie says.
Patients have largely been excluded from trials since they are “usually aimed at patients with amnestic Alzheimer’s with low scores on memory tests,” La Joie adds. “However, at UCSF we are considering treatments for patients with PCA and other non-amnestic variants.”
A more comprehensive understanding of PCA is “crucial for advancing both patient care and for understanding the processes that drive Alzheimer’s disease,” concludes senior author Gil Rabinovici, M.D., director of the UCSF Alzheimer’s Disease Research Center. “It’s critical that doctors learn to recognize the syndrome so patients can receive the correct diagnosis, counseling and care.”
“From a scientific point of view, we really need to understand why Alzheimer’s is specifically targeting visual rather than memory areas of the brain. Our study found that 60% of patients with PCA were women – better understanding of why they appear to be more susceptible is one important area of future research.”
The study is published in The Lancet Neurology.
