In a recent study, Understanding how MS does this may drive new treatment strategies, said the authors of the study, which was published online in Annals of Neurology. Regarding current treatments, they added, the availability of new disease-modifying Alzheimer’s disease therapies increases the importance of early diagnosis in cognitively impaired people including those with MS.
Confirmatory Studies Needed
“Replication and confirmation of these findings, including in studies representative of the real-world Alzheimer’s population in race/ethnicity and sex/gender, are needed before any clinical implications can be drawn,” said Claire Sexton, DPhil, Alzheimer’s Association senior director of scientific programs and outreach. She was not involved with the study but was asked to comment.
The study’s most important immediate implication, said Dr. Sexton, is that it “opens the door to questions about why MS may be associated with Alzheimer’s risk.”
Alzheimer's Association
Dr. Claire Sexton
Anecdotal Observation
Although life expectancy for people with MS is increasing, the authors, led by Matthew R. Brier, MD, PhD, an assistant professor at Washington University in St. Louis, Missouri, said they have seen no concomitant rise in Alzheimer’s disease dementia among their patients with MS. This anecdotal observation fueled their hypothesis that Alzheimer’s disease pathology occurs less frequently in this population.
To test their hypothesis, the investigators sequentially enrolled 100 patients with MS (age 60 years or older), along with 300 non-MS controls matched for age, sex, apolipoprotein E (apoE) proteotype, and cognitive status. All participants underwent the Mini-Mental State Examination (MMSE) and PrecivityAD2 (C2N Diagnostics) blood testing.
Washngton University
Dr. Matthew R. Brier
Overall, patients with MS had lower p-tau217 (t = 3.76, P = .00019) and amyloid probability score 2 (APS2; t = 3.83, P = .00015) ratios than did those without MS. APS2 combines p-tau217 ratio with Abeta42/40 ratio. In addition, APS2 and p-tau217 ratios were lower in patients with MS and ApoE3/apoE3 or apoE3/apoE4 proteotype. MMSE scores were also slightly lower in the MS cohort: 27.6 versus 28.44 for controls. Of 11 patients with MS who underwent Pittsburgh Compound B (PiB) positron emission tomography (PET), nine had congruent PiB PET and plasma results.
When the investigators applied clinical cutoffs, 7.1% of patients with MS were APS2-positive, versus 15.3% of controls (P = .0043). The corresponding figures for p-tau217 ratio positivity were 9% and 18.3%, respectively (P = .0024). Mean Abeta42/40 scores showed no difference between groups.
Patients with MS and positive amyloid biomarkers often had atypical MS features at diagnosis. Compared with biomarker-negative patients with MS, odds ratios for having at least two atypical MS features at diagnosis among APS2-positive and p-tau217 ratio-positive patients with MS were 23.3 and 11.38, respectively.
Data regarding the actual incidence of Alzheimer’s disease among people with MS are scarce and conflicting. An autopsy study published in Annals of Neurology in 2008 revealed the expected rate of amyloid pathology in MS brain tissue, along with extensive microglia activation. In a PET study published in Annals of Neurology in 2020, however, researchers found less amyloid pathology among patients with MS than those without, but little difference in tau pathology.
Because MS and Alzheimer’s disease can each cause cognitive impairment, the rate of co-occurrence of MS and Alzheimer’s disease has been difficult to ascertain without accurate biomarkers. But, the authors said, the advent of disease-modifying therapies makes identifying early Alzheimer’s dementia in MS patients relevant.