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Memory was preserved over time in people who had primary progressive aphasia (PPA) with Alzheimer's disease, a small study showed.

Episodic memory was preserved at initial testing and did not decline 2.35 years later, at which time PPA symptoms had been present for 6.26 years, though language skills fell significantly, reported M. Marsel Mesulam, MD, of Northwestern University Feinberg School of Medicine in Chicago, and co-authors in .

"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," Mesulam said in a statement. "This has been difficult to determine because most memory tests rely on verbal skills that these people have lost or are losing."

PPA is a neurodegenerative condition characterized by prominent language problems that worsen over time. About 40% of patients with PPA have atypical manifestations of Alzheimer's disease, often with a logopenic variant of PPA.

The study included 17 PPA patients with Alzheimer's disease who were compared with 14 people who had typical Alzheimer's disease. Participants with PPA came from the Northwestern and had autopsy or biomarker evidence of Alzheimer's disease and at least two consecutive visits with language and memory assessments. Alzheimer's pathology was based on autopsy in eight participants, cerebrospinal fluid biomarkers in three, and amyloid PET in six. Ten participants were men, and 11 had logopenic PPA. Age at symptom onset ranged from 47 to 74, with an average of 59.

The group with typical Alzheimer's included eight men and six women from the Northwestern who had Alzheimer's disease as their principal neuropathologic diagnosis at autopsy. Mean age of symptom onset was 66. In this group, both verbal memory and language function declined over time with equal severity.

Imaging, done only on the PPA group, showed asymmetric left-sided mediotemporal atrophy. On autopsy, both groups had bilateral hippocampo-entorhinal neurofibrillary degeneration. Compared with the typical Alzheimer's group, the PPA group had lower incidence of mediotemporal TDP-43 pathology and a lower frequency of APOE4 genotype.

"Perhaps the most intriguing finding is that the preservation of memory in the PPA-Alzheimer's disease group is seen despite similarly widespread pathology in medial temporal lobe structures in both groups," noted Seyed Ahmad Sajjadi, MD, PhD, of the University of California Irvine, and co-authors in an . "Therefore, the medial temporal lobe structures in the PPA-Alzheimer's disease patients could be considered resilient, and not resistant, to Alzheimer's pathology."

Lack of right-sided medial temporal lobe atrophy in the PPA group corroborates this idea: "It implies an uncoupling of neurodegeneration and pathology in those with PPA-Alzheimer's disease," the editorialists wrote.

"Combined with the more widespread cortical atrophy of the left hemisphere in the PPA group, it seems reasonable to conclude that neurodegeneration, and not mere presence of pathology, is what correlates with clinical presentation in these patients," they added. "This is an important notion in an era of development of targeted therapies that are increasingly aimed at those with no or minimal cognitive impairment."

Limitations of the study include its relatively small sample size. Autopsies were not available for all PPA cases. In addition, episodic memory was evaluated with different tests in the two groups.

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