Familial Alzheimer’s Patients May Show Atypical Symptoms, Study Reports

Patients with inherited forms of Alzheimer’s disease have neurological symptoms other than memory loss, suggesting that physicians need watch for less typical symptoms when suspecting familial Alzheimer’s in a patient. While the study also found atypical symptoms can differ among patient groups, a comment suggested that such differences partly reflect the large variability in how this disease affects people.

A better understanding of the reasons for these differences would benefit patients with familial Alzheimer’s, and likely those with sporadic forms of the disease too.

The study, “Neurological manifestations of autosomal dominant familial Alzheimer’s disease: a comparison of the published literature with the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS)” appeared in the journal The Lancet Neurology.

Researchers at Washington University School of Medicine first explored published data on neurological symptoms other than memory loss in patients with dominantly inherited familial Alzheimer’s disease, and noted relatively frequent reports of atypical symptoms.

Many the published studies were small, however, and included patients with widely varying disease severity. To get a better picture of how common such problems are, the research team turned to the Dominantly Inherited Alzheimer Network observational study (DIAN-OBS).

They selected 107 patients, from the U.S., Europe, and Australia, who were followed in this study between Feb. 29, 2008, and July 1, 2014. They also compiled previously published data on 753 individuals with familial Alzheimer’s to serve as a comparison group.

Researchers soon noted that the rates at which certain symptoms appeared in the two groups differed considerably.

In the DIAN-OBS study, the most common cognitive symptoms other than memory loss were visual agnosia (an inability to understand visual information), present in 55.1%; aphasia, or difficulties in understanding or producing language, 57.9%; and behavioral problems, seen in 61.7%.

The published data group, however, showed much lower rates for each of these three symptoms: 5.6%, 23%, and 31.7%, respectively.

Looking at neurological symptoms not related to cognition, the reverse was seen. In the DIAN-OBS group, such symptoms were rare. Researchers found muscle spasms in 9.3%, seizures in 2.8%, and parkinsonism in 11.2%.

In the published patient sample, 15% had spasms, 20.3% seizures, and 12.5% had parkinsonism.

These large differences could be explained, in part, by differences in the composition of the groups. In the DIAN-OBS study, patients had less advanced disease than those in the published studies.  DIAN-OBS patients were also observed for a shorter time than the average patient in the published study group.

Various forms of bias could also have affected results, and the researchers noted that movement symptoms, including spasms and seizures, were more common among patients diagnosed at younger ages. Stroke was more common in those diagnosed at older ages.

Researchers did not find any links between particular symptoms and type of Alzheimer’s mutations.

In a linked comment, published in the same journal, Wiesje M Van der Flier with the VU University Medical Center in Amsterdam agreed that various forms of research bias likely made up much of the differences.

She also brought up another study, published in Lancet Neurology, “Clinical phenotype and genetic associations in autosomal dominant familial Alzheimer’s disease: a case series.” While the study had a somewhat different approach, it also looked at particular neurological symptoms in patients with dominant familial Alzheimer’s disease.

This study reported that myoclonus, a type of muscle spasm, was observed in 33% of people with APP mutations and 47% with PSEN1 mutations — by all means, higher than both patient groups in the other study.

According to Van der Flier, such differences come down to familial Alzheimer’s disease being a rather variable condition, and demands awareness of its less typical Alzheimer features to ensure correct diagnosis.

Although the second study did find associations between symptoms and mutation types, a large part of the differences could not be explained, indicating that environmental or metabolic factors contribute to symptom differences — or as-yet unaccounted genetic changes.

“The notion that we will find one treatment that cures all patients with Alzheimer’s disease is quickly losing ground,” Van der Flier wrote, calling for more studies into the processes causing such differences, as this could lead to more precise treatments.