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Exploring a rare form of Alzheimer’s disease affecting younger individuals

Published June 12th, 2024

Alzheimer’s disease, the most common form of dementia in the United States, affects millions of Americans, predominately striking after the age of 60. However, there is a lesser-known rare variant of Alzheimer’s called Posterior Cortical Atrophy (PCA) that makes up about 5% of cases. PCA stands out due to its unique symptoms, particularly related to vision, and its tendency to affect younger individuals. At Private Health Management (PHM), our team of researchers and clinicians stays up to date on the latest developments related to dementia and monitors the treatment landscape for clinical trials and emerging therapies. In this article, we offer insights into PCA, covering symptoms, diagnosis, and disease management options.

PCA: The Visual Dementia
Posterior Cortical Atrophy means ‘back of the brain shrinkage’ as it involves the progressive loss of brain cells in regions located toward the back of the brain, including the occipital and parietal lobes. This is different from other forms of Alzheimer’s, which are characterized by loss of brain cells in the frontal lobe, parietal lobe, and hippocampus. PCA is commonly called “the visual dementia” because it affects regions of the brain that are involved in processing visual and sensory information.

Regions of the brain affected by Alzheimer’s.*
Regions of the brain affected by PCA.*

People living with PCA often experience a progressive decline in vision and/or literacy skills including spelling, writing and arithmetic. Many people go to see an eye doctor first, thinking that their difficulties are due to a problem with their eyes and that they may need new glasses. However, their visual issues are not related to their eyes, but rather to the fact that the shrinking brain can no longer interpret and process the information received from the person’s healthy eyes. PCA is also unique from other types of Alzheimer’s in that the age of onset tends to be younger, with symptoms often starting between the ages of 50 and 65 years.

While PCA is often considered to be a rare form of Alzheimer’s, it can also be caused by damage that occurs due to other neurodegenerative diseases. In about 80% of cases, PCA is caused by changes to brain cells that are similar to changes that occur in Alzheimer’s. Scientists are not sure what causes cell death and tissue loss in the Alzheimer’s brain, but amyloid-beta (Aβ) plaques and Tau protein tangles are prime suspects. Abnormal clusters of Aβ protein fragments build up as plaques between nerve cells in the brain, while twisted strands of Tau protein are found in neurofibrillary tangles present in dead and dying nerve cells.1

Symptoms
Common symptoms of PCA include difficulties or impairments with the following:

  • Reading and writing
  • Interpreting images or words
  • Judging distances and depth
  • Orientation
  • Recognition of objects and faces
  • Doing math or spelling words
  • Using tools and appliances
  • Blurry vision
  • Sensitivity to light
  • Finding words

Diagnosis of PCA
The accurate diagnosis of PCA may be delayed because the initial symptoms often include visual impairment that may be confused for common, age-related vision changes. PCA symptoms vary from person to person and change as the condition progresses, which can also make diagnosis challenging.

There is not a definitive test for PCA, and diagnosis often involves ruling out other potential causes for the symptoms, like infection, inflammation, stroke, or a brain tumor. Diagnosis includes evaluation by a neuropsychiatrist, blood tests, and brain imaging tests, including advanced imaging like FDG Amyloid PET CT scans.2

Disease Progression
PCA often begins with mild cognitive decline, including subtle difficulties managing complex visual tasks, finding the right words when speaking, odd visual sensations, and other visual difficulties. More moderate cognitive impairment causes problems with writing, speaking, and dealing with numbers and increasing visual difficulties may result in a need to stop driving. As the disease progresses, word finding, day-to-day memory, and general cognitive functions may become affected, and people develop the symptoms of typical Alzheimer’s. In the final stage of PCA, people lose the ability to respond to their environment, to carry on a conversation and, eventually, to control movement.3,4 Some people with PCA live approximately the same length of time as individuals with typical Alzheimer’s (on average 10–12 years following the onset of symptoms) while others live with the condition for longer.

Management of PCA
There are currently no treatments that can prevent or reverse the underlying causes of PCA. However, there are both non-medication management strategies and pharmacologic treatments that can improve quality of life and potentially slow progression of the disease.

Non-Medication Therapies

Non-medication options involve a variety of approaches to help manage the progressive symptoms of the disease.3,5 Occupational and physical therapy can provide coping skills and strategies for people who have developed trouble with movement. Personalized cognitive rehabilitation can help with mental stimulation and engaging in a rich learning environment, which is particularly useful during early to middle stages of the disease. Optimizing nutrition to maintain a balanced diet, getting adequate sleep, and exercising can enhance brain health, mood, and general fitness.

Medications

Several drugs called cholinesterase inhibitors are approved for treating Alzheimer’s and can be used for PCA, including donepezil (Aricept®), rivastigmine (Exelon®), and galantamine (Reminyl®). These drugs work by helping brain cells communicate with each other. They may help to improve symptoms for a time, but they do not stop the disease from getting worse. Some people find that their symptoms improve while taking these drugs, but others may not notice an effect.6

Recently, a monoclonal antibody therapy called lecanemab (Leqembi®) was approved for Alzheimer’s treatment. It is designed to target the build-up of Aβ protein, with the goal of slowing disease progression and potentially allowing patients to live independently for longer. Studies have shown that lecanemab slowed the rate of decline in people’s memory and thinking over 18 months and slowed down the rate of decline in people’s ability to carry out day-to-day activities. However, there are unfortunate and common side effects that occur with lecanemab called Amyloid-related imaging abnormalities (ARIAs). These include small brain bleeds (ARIA-H) and swelling (ARIA-E) that can be observed as changes to the brain on MRI scans. Roughly 1 in 8 people who received lecanemab developed ARIA-E. These reactions were most common in people who carried two copies of the APOE4 gene, a genetic variant linked to Alzheimer’s risk, so genetic sequencing can be used to help determine if a person may be at higher risk for these side effects.7

Other monoclonal antibodies targeting the Aβ protein are in development, including donanemab, which was recommended for approval by a panel of advisors in June of 2024, but has not yet been FDA-approved.

PHM helps manage the diagnosis and treatment of PCA and other forms of dementia
Private Health Management provides comprehensive guidance for people who have signs of cognitive decline and dementia. Our team coordinates testing, arranges for consultations with experts to obtain accurate diagnoses and to develop treatment strategies, and helps to monitor disease progression. In addition, we provide valuable support to people who have been diagnosed with PCA, Alzheimer’s, and other forms of dementia, including disease education, emotional support, and connections with specialized physical and occupational therapists.

*Images created with BioRender.com

References

  1. Soria Lopez, J. A., González, H. M. & Léger, G. C. Alzheimer’s disease. Handb Clin Neurol 167, 231–255 (2019).
  2. Wong, B. et al. Diagnostic evaluation and monitoring of patients with posterior cortical atrophy. Neurodegenerative Disease Management 9, 217–239 (2019).
  3. Rajaram Manoharan, S. V. R. & Munakomi, S. Posterior Cortical Atrophy. in StatPearls (StatPearls Publishing, Treasure Island (FL), 2024).
  4. Sebastian Crutch, Jill Walton, Amelia Carton, Tim Shakespeare. The Stages of Posterior Cortical Atrophy. https://www.raredementiasupport.org/wp-content/uploads/2020/03/The-Stages-of-Posterior-Cortical-Atrophy.pdf.
  5. Yong, K. X. X. et al. Diagnosis and Management of Posterior Cortical Atrophy. Curr Treat Options Neurol 25, 23–43 (2023).
  6. Deardorff, W. J., Feen, E. & Grossberg, G. T. The Use of Cholinesterase Inhibitors Across All Stages of Alzheimer’s Disease. Drugs Aging 32, 537–547 (2015).
  7. van Dyck, C. H. et al. Lecanemab in Early Alzheimer’s Disease. N Engl J Med 388, 9–21 (2023).

About the Author

Jimmy Ou, PhD

Senior Research Director

Dr. Ou, a Senior Research Director at PHM with over 20 years of academic and biopharma research experience, specializes in targeted therapeutics and neurological disorders. Jimmy holds a PhD in Molecular and Medical Pharmacology and a BS in Neuroscience from UCLA.