Could bizarre visual symptoms be a telltale sign of Alzheimer’s disease?

A team of international researchers, led by UC San Francisco, has completed the first large-scale study of posterior cortical atrophy, a puzzling constellation of visuospatial symptoms that presents as early symptoms of Alzheimer’s disease. These symptoms occur in up to 10% of cases of Alzheimer’s disease.

The study includes data from more than 1,000 patients across 36 sites in 16 countries. It is published in Neurology from the Lancet.

Posterior cortical atrophy (PCA) overwhelmingly predicts Alzheimer’s disease, researchers have found. Some 94% of PCa patients suffered from Alzheimer’s disease and the remaining 6% suffered from diseases such as Lewy body disease and frontotemporal lobar degeneration. On the other hand, other studies show that 70% of patients suffering from memory loss suffer from Alzheimer’s disease.

Unlike memory problems, PCA patients have difficulty judging distances, distinguishing between moving and stationary objects, and performing tasks like writing and retrieving a dropped object despite examination of the normal vision, said co-first author Marianne Chapleau, Ph.D., of UCSF. Department of Neurology, Center for Memory and Aging and Weill Institute for Neuroscience.

Most patients with PCA have normal cognition early on, but by the time of their first diagnostic visit, an average of 3.8 years after symptom onset, mild or moderate dementia was apparent with deficits identified in memory, executive function, behavior, speech and language. according to the researchers’ conclusions.

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

We need better tools and training to identify patients

“We need to raise awareness of PCA so that it can be reported by clinicians,” Chapleau said. “Most patients see their optometrist when they start experiencing visual symptoms and may be referred to an ophthalmologist who may also not recognize PCA,” she said. “We need better tools in the clinical setting to identify these patients early and offer them treatment.”

The average age of onset of PCA symptoms is 59 years, several years younger than that of typical Alzheimer’s disease. This is another reason why PCa patients are less likely to be diagnosed, Chapleau added.

Early identification of PCA could have important implications for the treatment of Alzheimer’s disease, said co-first author Renaud La Joie, Ph.D., also of the UCSF Department of Neurology and the memory and aging center. In the study, levels of amyloid and tau, identified in spinal fluid and imaging, as well as autopsy data, matched those found in typical Alzheimer’s cases.

As a result, patients with PCa may be candidates for anti-amyloid therapies, such as lecanemab (Leqembi), approved by the US Food and Drug Administration in January 2023, and anti-tau therapies, currently in currently undergoing clinical trials, both of which are considered to be more effective in the early stages of the disease, he said.

“Patients with PCA have more tau pathologies in the posterior parts of the brain, involved in processing visuospatial information, compared to those with other presentations of Alzheimer’s disease. This could make them better suited to anti-tau therapies,” he said.

Patients have mostly been excluded from the trials because they “are generally intended for amnestic Alzheimer’s patients with low scores on memory tests,” La Joie added. “However, at UCSF we are considering treatments for patients with PCA and other non-amnestic variants.”

A better understanding of PCA is “crucial to advancing patient care and understanding the processes that cause Alzheimer’s disease,” said lead author Gil Rabinovici, MD, director of the research center. on Alzheimer’s Disease from UCSF. “It is essential that doctors learn to recognize the syndrome so that patients can receive the appropriate diagnosis, advice and care.

“From a scientific perspective, we really need to understand why Alzheimer’s disease specifically targets visual areas rather than memory areas of the brain. Our study found that 60% of PCA patients were women – a Better understanding of why they appear to be more susceptible is an important area of ​​future research.