Posterior Cortical Atrophy (PCA)

What Causes Posterior Cortical Atrophy (PCA)?

Scientists don’t know what causes PCA. Because PCA is associated with Alzheimer’s disease in 80% of cases, some researchers believe that PCA is a sub-type of Alzheimer’s. However, PCA is sometimes associated with other disorders, such as Lewy body dementia or Creutzfeldt-Jakob disease.

In many cases, brain tissue affected by PCA shows an accumulation of abnormal protein tangles, the same kind of tangles that cause Alzheimer’s. Over time, these proteins interfere with the function of brain cells, and eventually, the cells die. As more cells die, the affected part of the brain shrinks, and the functions controlled by that part of the brain are impaired.

Despite the strong association with Alzheimer’s, PCA differs in some significant ways. PCA often emerges at an earlier age (between the ages of 50 and 65) than is typical for Alzheimer’s. PCA also affects a part of the brain that is not commonly affected by Alzheimer’s.

Is Posterior Cortical Atrophy (PCA) Hereditary?

Scientists have not identified any genes or genetic mutations consistently associated with PCA, so there is no evidence that the disorder is inherited.

How Is Posterior Cortical Atrophy (PCA) Detected?

There is no cure for PCA, and there is no treatment that will stop the progression of its symptoms. However, early detection of the disorder can help sufferers seek interventions to improve their conditions

Because early symptoms of PCA are typically related to vision, the disorder is often misdiagnosed as a vision problem.

Early signs of PCA often include:

• Blurred or double vision
• Difficulty following a line of text while reading
• Difficulty reaching for objects or other problems with depth perception
• Increased sensitivity to bright light sources or shiny objects

How Is Posterior Cortical Atrophy (PCA) Diagnosed?

There is currently no test or exam that will definitively detect PCA. As a result, the disorder is often misdiagnosed because its early symptoms look similar to those of visual or eye-related disorders.

As part of the diagnostic process, doctors will typically administer physical and neurological exams and laboratory tests to rule out conditions other than PCA that could be causing the symptoms.

• Blood and lab tests can be used to rule out other potential causes
• Doctors will usually administer an ophthalmologic examination to rule out eye-related causes
• Brain imaging scans such as magnetic resonance imaging (MRI) and positron emission tracer (PET) scans may be used to look for evidence of PCA or other brain disorders.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Posterior Cortical Atrophy (PCA) Treated?

No treatment will slow, stop, or reverse the effects of PCA. Medications that show promise in treating Alzheimer’s and other forms of dementia may be used, but research has not yet shown that these treatments are effective for PCA. Other PCA treatment options focus on directly treating symptoms and managing their effects.

Medications

• Cholinesterase inhibitors are sometimes prescribed for mild to moderate Alzheimer’s disease and may also be prescribed for PCA. These drugs include galantamine, rivastigmine, and donepezil. While scientists do not fully understand how cholinesterase inhibitors work, research shows that they prevent the breakdown of a brain chemical called acetylcholine, which is vital to memory and thinking. However, these medications have not yet been proven effective in treating PCA.
• Antidepressants such as may citalopram, paroxetine, or sertraline may be used to treat symptoms such as depression or mood changes.

How Does Posterior Cortical Atrophy (PCA) Progress?

PCA symptoms become progressively worse over time, and in some cases, symptoms become so severe that sufferers require full-time care. In cases where PCA is associated with Alzheimer’s, symptoms will eventually progress to the debilitating effects of that disease. Survival in these cases is usually 10-20 years after the initial onset of symptoms. However, some people with PCA survive longer.

Potential long-term complications of PCA include:

• Memory deficits
• Dementia
• Seizures
• Infections or illnesses such as pneumonia
• Accidents or falls
• Risky behavior that can endanger the sufferer or others
• Total loss of the ability to communicate

How Is Posterior Cortical Atrophy (PCA) Prevented?

There is no known way to prevent PCA. In addition, the cause of PCA remains unknown, so there are no avoidable risk factors associated with the disorder.

If you have a family history of PCA or degenerative neurological disorders, a genetic counselor can help you decide if you should undergo genetic testing.

Posterior Cortical Atrophy (PCA) Caregiver Tips

Taking care of a loved one with PCA can be extremely taxing, both physically and emotionally. To help yourself and your loved one cope with the effects of the disease, keep these tips in mind:

• Learn all you can about PCA. Some PCA symptoms can be shocking, and you’ll be better equipped to deal with them if you understand their cause. For example, your loved one may exhibit agitation, aggression, or socially unacceptable behavior. It’s crucial that you not take this behavior personally and understand that it is part of the disease.
• Take care of yourself. Caregivers for people with PCA are at particular risk of physical and mental health issues themselves. So don’t hesitate to take time for yourself away from your loved one when you can, and seek help from a support group, either locally or online.

Many people with PCA also suffer from other brain and mental health-related issues, a condition called co-morbidity. Here are a few of the disorders commonly associated with PCA:

• People with PCA are at increased risk for depression or an anxiety disorder.
• PCA can occur at the same time as Alzheimer’s disease and other types of dementia.

Posterior Cortical Atrophy (PCA) Brain Science

In most cases, PCA shows the same development of protein plaques in the brain that are characteristic of Alzheimer’s. Although most people with Alzheimer’s don’t experience PCA, many scientists believe that the underlying causes of Alzheimer’s may also be at play in PCA.

Years before Alzheimer’s symptoms start to appear, subtle changes occur in the brain:

• Toxic fragments of beta-amyloid protein trigger neurological damage in the brain. Clumps of protein form “amyloid plaques” that build up between neurons.
• Tau is a necessary protein for healthy brain cells. However, in Alzheimer’s disease, the protein becomes deformed and tangled, preventing tau from doing its job.
• Amyloid plaques and tau tangles create a toxic environment in the brain, causing neurons to wither and lose their connections to neighboring neurons. PCA results when this happens in the rear (posterior) part of the brain.

Researchers have tried targeting beta-amyloid and tau in an attempt to treat Alzheimer’s disease. So far, these experimental therapies have been unsuccessful.

Clinical trials are also underway to find preventative ways to block the formation of amyloid plaques in the brain. In addition, researchers are studying whether medications approved for other diseases may help treat Alzheimer’s.

Posterior Cortical Atrophy (PCA) Research

Title: Early-onset Alzheimer’s Disease Phenotypes: Neuropsychology and Neural Networks (EOAD-Subtype)

Stage: Recruiting

Principal investigator: Mario F. Mendez, MD, PhD

UCLA Department of Neurology

Los Angeles, CA

Unlike the usual late-onset Alzheimer’s disease (LOAD), early-onset AD (EOAD), with onset before age 65, includes a high percentage of phenotypic variants. These non-familial variants (vEOAD) present not with progressive memory loss but with language, visuospatial, or other cognitive difficulties. AD is now understood as a disorder that manifests with disturbed cognition reflecting disturbed neural networks. A multivariate analysis of neuropsychological tests, the “gold standard” for objectively defining neurocognitive impairments, coupled with structural and functional neuroimaging analysis of connectomes, can identify the neurocognitive-neural network profiles of vEOAD patients, compared to those with typical AD. This knowledge can increase our understanding of the heterogeneity of AD and how it causes disease.

This study hopes to show that vEOAD constitutes a “Type 2 AD” by (1) defining the neuropsychological components of Type 2 AD and (2) understanding the anatomy and atrophy of the brains of vEOAD patients. Together, these components can outline the neurocognitive-neural network profile of Type 2 AD.

In addition to information that can help diagnose and manage EOAD, this study can stimulate novel research into the reasons for this neurobiological heterogeneity in AD and could potentially lead to interventions based on alternate neurocognitive-neural network profiles.

Title: Longitudinal Imaging of Microglial Activation in Different Clinical Variants of Alzheimer’s Disease (ADVISe)

Stage: Recruiting

Contact: Aubrey S Johnson

Columbia University Irving Medical Center

New York, NY 

The purpose of this study is to determine how inflammation is related to other changes in the brain that occur during the progression of Alzheimer’s disease. In addition, the investigators are also studying how inflammation is related to the symptoms that first occur in patients with Alzheimer’s disease (AD). For this reason, the investigators are asking people with different versions of Alzheimer’s disease to participate. This includes patients with either:

• Posterior cortical atrophy – a version of Alzheimer’s disease with vision difficulties
• Logopenic variant primary progressive aphasia – a version of Alzheimer’s disease with language difficulties
• Amnestic Alzheimer’s disease – a “typical” version of Alzheimer’s disease with memory difficulties

The investigators are also enrolling older adults with normal visual, language, and memory functions.

This study is being conducted to learn about inflammation in Alzheimer’s disease so that the investigators can find out new ways to treat patients with this disease. Because Alzheimer’s disease usually causes slow changes to the brain over time, in this study, the investigators will perform different tests and then repeat some of them two years later.

Inflammation can be measured using a type of brain scan called a positron emission tomography (PET) scan. A PET scan uses very small amounts of a radioactive drug injected into a vein to create a unique picture of the brain. The inflammation PET scan uses a drug called ER176. ER176 is an experimental drug but has been used in several human studies before. Once in the body, ER176 sticks to areas with lots of inflammation, and the PET scan allows us to see these areas.

Inflammation can also be measured by looking at specific proteins in the spinal fluid. The investigators need to perform a lumbar puncture (spinal tap) to measure these proteins in the spinal fluid. Specific genes inherited from parents influence the amount of inflammation in the body. The investigators can study how genes affect inflammation in Alzheimer’s disease by doing genetic tests on blood collected from the vein.

The investigators can study how genes affect inflammation in Alzheimer’s disease by doing genetic tests on blood. The investigators will also be testing blood for severe acute respiratory syndrome (SARS)- CoV-2 (the virus that causes COVID-19) antibodies. The investigators want to see if exposure to the virus that causes COVID-19 changes the amount of inflammation in the brain or not.

Along with inflammation, Alzheimer’s disease is also associated with the build-up of the proteins amyloid and tau in the brain. The investigators can measure these proteins using PET scans. The amyloid PET scan uses a drug called florbetaben that the FDA has approved to help diagnose Alzheimer’s disease. The tau PET scan uses a drug called MK-6240. Like ER176, MK-6240 is experimental but has been used in several human studies before.

A brain MRI creates a high-resolution picture of the brain. The brain MRI helps the investigators get more information from the PET scans and shows the investigators the size and appearance of different brain structures. When someone has Alzheimer’s disease, some of these brain structures get smaller or have altered appearance on MRI.

Title: UPenn Observational Research Repository on Neurodegenerative Disease (UNICORN)

Stage: Recruiting

Principal investigator:  Murray Grossman, MD  

University of Pennsylvania

Philadelphia, PA

The Principal Investigator (PI) at the University of Pennsylvania seeks to understand neurodegenerative diseases better and is continually expanding research efforts and collaborations regarding the factors that may contribute to these illnesses. Investigators aim to better understand the basis of neurodegenerative conditions by creating a multimodal repository, including clinical data such as demographic characteristics, vital signs, and motor scales; cognitive and speech data; neuroimaging data; and biological specimens with associated biofluid biomarkers and genetic data. Investigators pursue acquiring these data from neurodegenerative disease patients, people at risk for neurodegenerative disease due to family history, and unaffected adults. Targeted conditions include frontotemporal degeneration (FTD), primary progressive aphasia PPA), amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), familial frontotemporal lobar degeneration (fFTLD), non-amnestic variants of Alzheimer’s disease, including logopenic progressive aphasia and posterior cortical atrophy, and Lewy body disease. This study aims to collect clinical and cognitive data, imaging data, and biospecimen samples from people whose background can inform research and treatment of neurodegenerative illnesses and make these samples and data available to qualified researchers at the University of Pennsylvania and collaborating academic centers and industry partners.