There are five different diseases that attack language areas in the left hemisphere of the brain that slowly cause progressive impairment of language known as primary progressive aphasia (PPA), according to a new study in Northwestern Medicine.
We discovered that each of these diseases affects a different part of the language network. In some cases, the disease affects the area responsible for grammar, and in others, the area responsible for understanding words. Each disease develops at a different rate and has different implications for intervention. “
Marcel Mesulam, lead author of the study and director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University
This study is based on the largest set of PPA autopsies -; 118 cases -; ever compiled.
It will be published April 20 in Brain magazine.
“Patients were followed for more than 25 years, so this is the most comprehensive study to date on life expectancy, type of language impairment, and relationship of disease to details of language impairment,” said Mesulam, chair of Northwestern’s Division of Behavioral Neuroscience. Feinberg University School of Medicine.
Patients with PPA were prospectively enrolled in a longitudinal study that included language testing and imaging of brain structure and function. The study involved consent to donate brain upon death.
An estimated 1 in 100,000 people have PPA, Mesulam said.
The initial symptoms of PPA can be subtle and are sometimes attributed to anxiety or throat problems. Even specialists may fail to make a timely diagnosis. In 40% of cases of PPA, the underlying disease is an unusual form of Alzheimer’s disease. It is unusual because it impairs language rather than memory, and because it can start much earlier when a person is under 65.
In 60% of cases, the diseases causing PPA belong to a completely different group of conditions called frontotemporal lobe degeneration (FTLD). Although most people have not heard of this, cases of frontotemporal lobe degeneration are responsible for about 50% of all types of dementia that begin before the age of 65. An accurate diagnosis can now be reached using new imaging and biochemical methods.
Once the underlying disease has been diagnosed, there are many different approaches to the disease (medication) and symptom level.
“The trick is to approach the PPA on both levels simultaneously,” Mesulam said.
If Alzheimer’s disease is the cause, the patient can be treated with medication and directed to clinical trials. At the symptomatic level, an individual who has difficulty with grammar and finding words can receive targeted speech therapy. People with an understanding of words will receive a different type of speech therapy or possibly transcranial magnetic stimulation, which appears to work best for this specific deficiency. Anxiety about finding words can be treated with anti-anxiety medications and behavioral therapy.
The next step in research is to improve diagnostic accuracy with new biomarkers in order to determine whether the cause of a patient’s PPA is Alzheimer’s disease or FTLD. Northwestern University scientists also want to find appropriate drug treatments for each of the underlying diseases and individualized interventions for PPA. Another goal is to design episodic non-pharmacological interventions based on the nature of language impairment.
Mesolam, mm. , and others. (2022) Pathological neural signatures of survival, atrophy, and language in primary progressive aphasia. brain. doi.org/10.1093/brain/awab410.