Remedy with the selective serotonin reuptake inhibitor (SSRI) escitalopram lowers amyloid-beta-42 (Aβ42) ranges in the cerebrospinal fluid (CSF) of cognitively in style older adults, suggesting a doable role for these capsules in the prevention of Alzheimer’s disease (AD), researchers speak.
On the opposite hand, it remains to be viewed whether the “somewhat modest” reduction in CSF Aβ42 will translate into medical merit, they acknowledge.
Dr Yvette Sheline
“We stare two doable ideas to arrangement this plight,” Yvette Sheline, MD, University of Pennsylvania, Philadelphia, Pennsylvania, suggested Medscape Medical Recordsdata. “One is to occupy greater the drug make by finding a molecule that more namely binds to the receptors that induce the amyloid-beta reduction,” she acknowledged.
“The loads of avenue would be to combine it with one more effective drug and thereby carry out additive reductions in amyloid. For instance, it’s a ways that you would possibly per chance per chance well be mediate of that combining it with an antiamyloid drug just like an antibody would possibly per chance per chance well occupy greater the potency,” she added.
The mediate about used to be published on-line September 10 in Neurology.
In retrospective learn, in contributors who had a history of remedy with SSRIs, there used to be a major reduction in amyloid plaque binding, as evidenced on positron-emission tomography.
To boot to, learn in mice occupy shown that SSRIs occupy greater alpha-secretase, which causes the cleavage of the amyloid precursor protein, ensuing in much less amyloid.
Within the most contemporary mediate about, Sheline and colleagues examined the implications of escitalopram in 114 cognitively in style adults frail 50 years and older.
They used lumbar puncture to pick out CSF Aβ42 ranges before and after the patients obtained escitalopram 20 mg/day for 2 or 8 weeks or 30 mg/day for 8 weeks. Elevate a watch on contributors got placebo.
When the 2 dose regimens were evaluated collectively, there used to be a major total 9.4% share level better reduction in CSF Aβ42 in escitalopram-handled patients when in contrast with placebo-handled patients (P < .001; 95% CI, 4.9% to 14.2%; Cohen’s d = 0.81).
Positive baseline amyloid-beta convey (CSF Aβ42 ranges <250 pg/mL) correlated with smaller Aβ42 reduction (P = .006; 95% CI, -16.7% to -0.5%; d = -0.52) compared with negative baseline amyloid status (CSF Aβ42 levels >250 pg/mL).
“Construction of safe and effective therapeutic approaches that can lower Aβ ranges even modestly would possibly per chance per chance well stop pathological amyloid accumulation and the next cascade of neuronal ruin which would possibly per chance per chance well stop or leisurely progression to symptomatic AD,” the investigators attain.
Clinical Affect Collected Unclear
Reached for instruct, Vijay K. Ramanan, MD, PhD, Division of Neurology, Mayo Hospital, Rochester, Minnesota, smartly-known that some literature from model system and human learn, including the most contemporary mediate about, level to that SSRIs would possibly per chance per chance well have an effect on amyloid pathophysiology and occupy the doable to handbook underlying disease mechanisms.
On the opposite hand, he added, “It is level-headed unclear what any modest reducing of amyloid in the CSF in this atmosphere would possibly per chance per chance well imply for longer-timeframe amyloid ranges in the brain parenchyma or, for that matter, for diverse AD biomarkers and associated medical outcomes.”
Ramanan identified that few medicines designed to lower brain parenchymal amyloid were very effective at doing so, and whether such reducing would possibly per chance per chance well cease up in mountainous, clinically meaningful merit to patients “is level-headed an awesome negate.”
Furthermore commenting for Medscape Medical Recordsdata, Constantine G. Lyketsos, MD, professor of psychiatry and behavioral sciences, Johns Hopkins Medication, Baltimore, Maryland, described the mediate about as “crucial.”
“Within the broader context, we and loads others occupy shown reasonably conclusively that many of us that spin on to get dementia develop peculiar moodlike symptoms, just like irritability and persona changes, years before they develop reminiscence symptoms,” he acknowledged.
“The hunt for is that these moodlike symptoms are a reflection of the underlying Alzheimer’s that starts with mood symptoms then progresses to reminiscence symptoms. And there’s increasingly proof that escitalopram and loads of medicines from this class alleviate these mood symptoms, that are no longer conventional for despair,” Lyketsos added.
This recent learn “strengthens the look for that no longer handiest would possibly per chance per chance well we be ready to get the mood symptoms better, but that these medicines would possibly per chance per chance well alleviate the underlying amyloid biology, therefore being a real diagram of stopping reminiscence loss and dementia. That is no longer any longer been shown till this paper, which is so crucial.”
The mediate about obtained no funding. Sheline, Ramanan and Lyketsos make no longer occupy any disclosed no associated financial relationships.
Neurology. Printed on-line September 10, 2020. Summary