Summary: While 40% of people with primary progressive aphasia have underlying Alzheimer’s disease, a new study suggests they may not develop the memory problems associated with Alzheimer’s.
Primary progressive aphasia is a rare neurodegenerative condition characterized by prominent language problems that worsen over time. About 40% of people with the condition have underlying Alzheimer’s disease. But a new study has found that people with the condition may not develop the memory problems associated with Alzheimer’s disease. The study is published in the January 13, 2021, online issue of Neurology.
“While we knew that the memories of people with primary progressive aphasia were not affected at first, we did not know if they maintained their memory functioning over years,” said study author M. Marsel Mesulam, M.D., of Northwestern University Feinberg School of Medicine in Chicago and a Fellow of the American Academy of Neurology. “This has been difficult to determine because most memory tests rely on verbal skills that these people have lost or are losing.”
The study included 17 people with primary progressive aphasia associated with Alzheimer’s disease. They were compared to 14 people who had typical Alzheimer’s disease with memory loss.
Researchers tested memory skills of the people with primary progressive aphasia by showing them pictures of common objects. After waiting 10 minutes, they were shown the same pictures along with others and had to indicate whether they had seen the picture before. This test was given once and then again an average of 2.4 years later. The people with typical Alzheimer’s disease listened to a list of common words and were later given the same words along with others and asked to choose the ones they had heard before. They were tested once and then again an average of 1.7 years later.
Both groups also had tests of their language skills. Brain scans were taken of the people with primary progressive aphasia to look at how the disease was affecting their brains, especially in the areas related to memory.
The people with primary progressive aphasia had no decline in their memory skills when they took the tests a second time. At that point, they had been showing symptoms of the disorder for an average of six years. In contrast, their language skills declined significantly during the same period. For the people with typical Alzheimer’s disease, their verbal memory and language skills declined with equal severity during the study.
Researchers had brain autopsies from eight of the people with primary progressive aphasia and all of the people with typical Alzheimer’s disease. The people with primary progressive aphasia had similar amounts of the plaques and tangles that are signs of Alzheimer’s disease as the people with typical Alzheimer’s, Mesulam said. Left sided asymmetry of brain shrinkage and a lower incidence of brain proteins known as ApoE4 and TDP-43 were identified as potential contributors to the preservation of memory in this rare type of Alzheimer’s disease.
“More research is needed to help us determine what factors allow these people to show this resilience of memory skills even in the face of considerable Alzheimer’s disease pathology in the brain,” Mesulam said.
Limitations of the study are the relatively small sample size and that autopsies were not available for all of the primary progressive aphasia cases.
Funding: The study was supported by the National Institute on Deafness and Other Communication Disorders, National Institute of Neurological Disorders and Stroke, The Davee Foundation and The Jeanine Jones Fund.
About this memory research news
Contact: Renee Tessman – AAN
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Original Research: Closed access.
“Memory resilience in Alzheimer’s disease with primary progressive aphasia” by M.-Marsel Mesulam, Christina Coventry, Alan Kuang, et al. Neurology
Memory resilience in Alzheimer’s disease with primary progressive aphasia
To determine whether memory is preserved longitudinally in primary progressive aphasia (PPA) associated with Alzheimer’s disease (AD), and to identify potential factors that maintain memory despite underlying neurofibrillary degeneration of mediotemporal memory areas.
Longitudinal memory assessment in 17 PPA patients with autopsy or biomarker evidence of AD (PPA-AD) and 14 patients with amnestic dementia of the Alzheimer type with AD at autopsy (DAT-AD).
In PPA-AD, episodic memory, tested with nonverbal items, was preserved at initial testing and showed no decline at retesting 2.35 ± 0.78 years later, at which time symptoms had been present for 6.26 ± 2.21 years. In contrast, language functions declined significantly during the same period. In DAT-AD, both verbal memory and language declined with equal severity. Although imaging showed asymmetric left sided mediotemporal atrophy in PPA-AD, autopsy revealed bilateral hippocampo-entorhinal neurofibrillary degeneration at Braak stages V and VI. In comparison to DAT-AD, however, the PPA-AD group had lower incidence of Apolipoprotein E4 and of mediotemporal TDP-43 pathology.
Memory preservation in PPA is not just an incidental finding at onset but a core feature that persists for years despite the hippocampo-entorhinal AD neuropathology that is as severe as that of DAT-AD. Asymmetry of mediotemporal atrophy and a lesser impact of Apolipoprotein E4 and of TDP-43 on the integrity of memory circuitry may constitute some of the factors underlying this resilience. Our results also suggest that current controversies on memory in PPA-AD reflect inconsistencies in the diagnosis of logopenic PPA, the clinical variant most frequently associated with AD.