Antidepressants for Dementia Prevention?

Medication with the selective serotonin reuptake inhibitor (SSRI) escitalopram lowers amyloid-beta-42 (Aβ42) phases in the cerebrospinal fluid (CSF) of cognitively typical older adults, suggesting a potential unbiased for these tablets in the prevention of Alzheimer’s illness (AD), researchers dispute.

However, it stays to be seen whether or now not the “pretty modest” cleave value in CSF Aβ42 will translate into clinical succor, they acknowledge.

“We seek for 2 potential ways to advance this dwelling,” Yvette Sheline, MD, College of Pennsylvania, Philadelphia, Pennsylvania, knowledgeable Medscape Clinical Files. “One is to amplify the drug cease by discovering a molecule that extra particularly binds to the receptors that induce the amyloid-beta cleave value,” she acknowledged.

“The different avenue would be to combine it with every other efficient drug and thereby manufacture additive reductions in amyloid. For instance, it is that you would possibly per chance well well presumably possess of that combining it with an antiamyloid drug reminiscent of an antibody would possibly per chance well well amplify the potency,” she added.

The quest for became as soon as published online September 10 in Neurology.

In retrospective compare, in folks who had a history of medication with SSRIs, there became as soon as a important cleave value in amyloid plaque binding, as evidenced on positron-emission tomography.

Besides, compare in mice possess confirmed that SSRIs amplify alpha-secretase, which causes the cleavage of the amyloid precursor protein, resulting in much less amyloid.

In the present seek for, Sheline and colleagues examined the effects of escitalopram in 114 cognitively typical adults archaic 50 years and older.

They historic lumbar puncture to acquire out CSF Aβ42 phases earlier than and after the patients got escitalopram 20 mg/day for 2 or 8 weeks or 30 mg/day for 8 weeks. Administration participants got placebo.

When the two dose regimens had been evaluated collectively, there became as soon as a important total 9.4% share level higher cleave value in CSF Aβ42 in escitalopram-handled patients when put next with placebo-handled patients (P < .001; 95% CI, 4.9% to 14.2%; Cohen’s d = 0.81).

Certain baseline amyloid-beta space (CSF Aβ42 phases <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).

“Pattern of protected and efficient therapeutic approaches that can well well lower Aβ phases even modestly would possibly per chance well well simply prevent pathological amyloid accumulation and the next cascade of neuronal hurt which can prevent or leisurely progression to symptomatic AD,” the investigators cease.

Clinical Impact Unruffled Unclear

Reached for comment, Vijay Good ample. Ramanan, MD, PhD, Department of Neurology, Mayo Sanatorium, Rochester, Minnesota, illustrious that some literature from mannequin system and human compare, including the present seek for, gift that SSRIs would possibly per chance well well simply affect amyloid pathophysiology and possess the skill to lead underlying illness mechanisms.

However, he added, “It’s miles mild unclear what any modest reducing of amyloid in the CSF in this setting would possibly per chance well well simply indicate for longer-time-frame amyloid phases in the mind parenchyma or, for that topic, for other AD biomarkers and linked clinical outcomes.”

Ramanan identified that few medicines designed to lower mind parenchymal amyloid had been very efficient at doing so, and whether or now not such reducing would possibly per chance well well simply consequence in gigantic, clinically important succor to patients “is mild a tricky project.”

Also commenting for Medscape Clinical Files, Constantine G. Lyketsos, MD, professor of psychiatry and behavioral sciences, Johns Hopkins Medication, Baltimore, Maryland, described the hunt for as “important.”

“In the broader context, we and heaps others possess confirmed barely conclusively that many folks that scurry on to acquire dementia obtain weird and wonderful moodlike signs, reminiscent of irritability and persona changes, years earlier than they obtain memory signs,” he acknowledged.

“The factor in is that these moodlike signs are a mirrored image of the underlying Alzheimer’s that begins with mood signs then progresses to memory signs. And there would possibly be extra and extra proof that escitalopram and other medicines from this class alleviate these mood signs, which will now not be typical for despair,” Lyketsos added.

This contemporary compare “strengthens the factor in that now not simplest would possibly per chance well well we be in a build to acquire the mood signs better, but that these medicines would possibly per chance well well alleviate the underlying amyloid biology, due to this truth being a upright scheme of battling memory loss and dementia. That is now not been confirmed except this paper, which is so important.”

The quest for got no funding. Sheline, Ramanan and Lyketsos don’t possess any disclosed no linked financial relationships.

Neurology. Printed online September 10, 2020. Summary

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