ECS Does Not Aggravate Alzheimer's Disease Pathology: New Study from Sweden

Out on PubMed, from researchers in Lund, Sweden, is this animal study:

The effect of electroconvulsive therapy on neuroinflammation, behavior and amyloid plaques in the 5xFAD mouse model of Alzheimer's disease.

Svensson M, Olsson G, Yang Y, Bachiller S, Ekemohn M, Ekstrand J, Deierborg T.Sci Rep. 2021 Mar 1;11(1):4910. doi: 10.1038/s41598-021-83998-0.PMID: 33649346 

The abstract is copied below:

Microglial cells are affected in Alzheimer's disease (AD) and interact with amyloid-beta (Aβ) plaques. Apart from memory loss, depression is common in patients with AD. Electroconvulsive therapy (ECT) is an anti-depressive treatment that may stimulate microglia, induce neuroinflammation and alter the levels of soluble Aβ, but the effects of ECT on microglia and Aβ aggregation in AD are not known. We investigated the short- and long-term effects of ECT on neuroinflammation and Aβ accumulation. 5xFAD mice received either electroconvulsive stimulation (ECS n = 26) or sham treatment (n = 25) for 3 weeks. Microglia and Aβ were analyzed in samples collected 24 h, 5 weeks, or 9 weeks after the last treatment. Aβ plaques and microglia were quantified using immunohistochemistry. The concentration of soluble Aβ and cytokines was quantified using ELISA and levels of Aβ aggregates were measured with Western Blot. Microglial phagocytosis of Aβ in the hippocampus was evaluated by flow cytometry in Methoxy-X04 injected mice 24 h following the last ECS treatment. Y-maze and Elevated plus maze were performed to study behavior after 5 weeks. We could not detect any significant short- or long-term effects of ECS on Aβ pathology or neuroinflammation, but ECS reduced abnormal behavior in the Elevated Plus maze.

The pdf is here.

...and from the text:

The 5xFAD strain is a mouse model with a fast development of AD pathology, showing accumulation of Aβ plaques and signs of neuroinflammation as early as 2–3 month of age and cognitive dysfunctions already at 5 months of age29–33. Tis makes the 5xFAD a suitable mouse model to study the effects of ECT on the development of amyloid plaque load, microglial neuroinflammation and cognitive dysfunctions seen in AD patients. Te aim of this study was to investigate the effects of ECT on neuroinflammation, cognition and Aβ pathology using 4–5.5 months-old 5xFAD mice.

...Discussion: Our study investigated the short- and long-term effects of ECS treatment on development of behavioral deficits, amyloid pathology and neuroinflammation in the 5xFAD mouse model of AD. We found no effects of ECS on Aβ pathology, microglial activity or cognitive function. ECS treatment did however reduce exploratory behavior, potentially suggesting a normalization of aberrant behavior in the 5xFAD mouse model of AD.

..Taken together, we could not detect any significant effects of ECS treatment on cognition, neuroinflammation, Aβ pathology nor microglial phagocytosis of Aβ in our 5xFAD mouse model of AD. This lack of detrimental effects is a promising indication for patients in need of this antidepressant treatment. Due to large variations within our experimental groups we cannot exclude any effects and more research will be needed to fully investigate the effects of ECT on AD pathology in this group of patients.

This is a remarkably clearly written and well- presented basic science paper. When I first read the abstract quickly, I was disappointed in the negative findings, expecting the authors to conclude that ECS (and, by translation, ECT) was not helpful for Alzheimer's disease (AD). But that was not the point, and the findings are actually encouraging, interpreted by the authors as evidence that ECS does not contribute to AD pathology, does lead to short-term neurogenesis, was helpful in one behavioral paradigm (interpreted as showing less "disinhibition") and did not lead to long-term memory impairment. (It is also good to be reminded of this mouse model of AD.)

Colleagues Brent Forester and George Petrides are leading a multi-center study investigating ECT for the treatment of agitation in AD; the current Swedish study is relevant and helpful basic science background for their clinical study.

I actually recommend a full read of this paper to all interested in ECT research, ~30 minutes.

(Yes, it is that good that even the methodological details are worth reading.)