According to a new study from Northwestern Medicine, five different diseases attack language areas in the left hemisphere of the brain and slowly cause progressive language disorders known as primary progressive aphasia (PPA).
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, in others the area responsible for understanding words. Each disease progresses at a different rate and has different implications for intervention.. »
Dr. M. Marsel Mesulam, lead study author and director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease, Northwestern University.
This study is based on the largest body of PPA autopsies –; 118 cases –; never collected.
It will be published on April 20 in the journal Brain.
“Patients have been followed for more than 25 years, so this is the most comprehensive study to date on life expectancy, type of language impairment and the relationship between disease and details of the language disorder,” said Mesulam, also chief of behavioral neurology at Northwestern University Feinberg School of Medicine.
Patients with APP were prospectively enrolled in a longitudinal study that included language testing and imaging of brain structure and function. The study included consent to brain donation at the time of death.
It is estimated that one in 100,000 people have ASF, Mesulam said.
Early symptoms of PPA can be subtle and sometimes attributed to anxiety or throat issues. Even specialists can fail to make a timely diagnosis. In 40% of ASF cases, the underlying disease is a very unusual form of Alzheimer’s disease. It is unusual because it impairs language rather than memory, and because it can start much earlier, when the person is under 65.
In 60% of cases, the diseases that cause APP belong to an entirely different group of conditions called frontotemporal lobar degeneration (FTLD). Although most people have not heard of it, frontotemporal lobar degeneration is responsible for about 50% of all dementias that occur before the age of 65. Accurate diagnosis can now be made using new imaging and biochemical methods.
Once the underlying disease is diagnosed, there are many different approaches at the disease (medication) and symptom level.
“The trick is to address PPA at these two levels simultaneously,” Mesulam said.
If Alzheimer’s disease is involved, a patient can be treated with drugs and referred to clinical trials. At the symptom level, a person who has difficulty with grammar and word search can receive targeted speech therapy. People who have word comprehension problems will receive another type of speech therapy or, perhaps, transcranial magnetic stimulation, which appears to be most effective for this particular deficit. Word-finding anxiety can be treated with anti-anxiety medications and behavioral therapy.
The next step in research is to improve diagnostic accuracy with new biomarkers to identify whether a patient’s APP is caused by Alzheimer’s disease or FTD. Northwestern scientists also want to find suitable pharmacological treatments for each disease underlying APP and to individualize interventions. Another goal is to design non-pharmacological symptomatic interventions according to the nature of language disorders.
Mesulam, MM. et al. (2022) Neuropathological imprints of survival, atrophy and language in primary progressive aphasia. Brain. doi.org/10.1093/brain/awab410.