Posterior Cortical Atrophy Predicts Alzheimer’s Disease

Conscious Perception Of Vision

A group of international researchers, led by UC San Francisco, has conducted the first large-scale study of posterior cortical atrophy, a perplexing constellation of visuospatial symptoms that appear as the early signs of Alzheimer’s disease. These symptoms appear in up to 10% of Alzheimer’s patients.

More than 1,000 patients’ records from 36 locations across 16 countries are included in the study.

Researchers discovered that posterior cortical atrophy (PCA) is a strong predictor of Alzheimer’s disease. 94% of PCA patients had Alzheimer’s pathology, whereas the remaining 6% had Lewy body disease or frontotemporal lobar degeneration. Other studies, however, indicate that 70% of people with memory loss have Alzheimer’s pathology.

PCA Visual and Cognitive Challenges

Patients with PCA, unlike those with memory problems, have difficulty judging distances, distinguishing between moving and stationary objects, and completing tasks such as writing and retrieving a dropped item, according to co-first author Marianne Chapleau, Ph.D., of the UCSF Department of Neurology, the Memory and Aging Center, and the Weill Institute for Neurosciences.

According to the researchers’ findings, most patients with posterior cortical atrophy have normal cognition early on, but by the time of their first diagnostic visit, which occurs an average of 3.8 years after symptom onset, mild or moderate dementia has developed, with deficits identified in memory, executive function, behavior, and speech and language.

At the time of diagnosis, 61% demonstrated “constructional dyspraxia,” an inability to copy or construct basic diagrams or figures; 49% had “space perception deficit,” difficulties identifying the location of something they saw; and 48% had “simultanagnosia,” an inability to visually perceive more than one object at a time. Additionally, 47% faced new challenges with basic math calculations and 43% with reading.

“We need more awareness of PCA so that it can be flagged by clinicians. 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,” she said. “We need better tools in clinical settings to identify these patients early on and get them treatment,”

said Chapleau.

Early Onset Identification

PCA has an average age of symptom start of 59, which is several years younger than conventional Alzheimer’s. This is yet another reason why PCA sufferers are underdiagnosed, according to Chapleau.

Early detection of PCA could have significant consequences for Alzheimer’s treatment, according to co-first author Renaud La Joie, Ph.D., also of the UCSF Department of Neurology and the Memory and Aging Center. The study discovered that levels of amyloid and tau in cerebrospinal fluid, imaging, and autopsy data were consistent with those found in normal Alzheimer’s cases.

As a result, patients with PCA may be candidates for anti-amyloid therapies, like lecanemab (Leqembi), approved by the U.S Food and Drug Administration in January 2023, and anti-tau therapies, currently in clinical trials, both of which are believed to be more effective in the earliest phases of the disease, he said.

“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 said.

Better Understanding Needed

Since most clinical trials are designed for patients with amnestic Alzheimer’s disease who score poorly on memory tests, most PCA patients have been excluded from them.

“However, at UCSF we are considering treatments for patients with PCA and other non-amnestic variants,”

La Joie said.

Better understanding of PCA is crucial for advancing both patient care and understanding the processes that drive Alzheimer’s disease, according to senior author Gil Rabinovici, M.D., head of the UCSF Alzheimer’s Disease Research Center. Doctors must learn to detect the syndrome so that patients can receive the proper 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,”

said Rabinovici.

  1. Marianne Chapleau, PhD, Renaud La Joie, PhD, Keir Yong, PhD, Federica Agosta, MD, Isabel Elaine Allen, PhD, Prof Liana Apostolova, MD, et al. Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis. Lancet Neurology Volume 23, Issue 2, P168-177, doi: DOI: 10.1016/S1474-4422(23)00414-3