Social isolation increases anxiety and asymmetry in brain atrophy in Alzheimer's disease

October 01, 2020

A study in mice conducted by the UAB shows that social isolation worsens the effects of Alzheimer's disease, with hyperactivity levels reaching up to twice as much as in the pathology itself

- The research also confirms an increase in the asymmetric atrophy of the hippocampus, a brain area central to memory

- The study was published in a special edition of Frontiers in Psychiatry entitled Death and Mourning Processes in the Times of the Coronavirus Pandemic (COVID-19), dedicated to assessing the effects of this pandemic

Researchers at the Department of Psychiatry and Legal Medicine and at the Institut de Neurociències (INc) of the Universitat Autònoma de Barcelona (UAB) have conducted a study which allows estimating, from the viewpoint of translational neuroscience, the effects of isolation in the current pandemic scenarios in elderly patients with dementia. The findings also may serve as a guide to the rethinking of vital conditions after the Covid-19 crisis. The study was published in Frontiers in Psychiatry, in a special edition of Frontiers in Psychiatry entitled Death and Mourning Processes in the Times of the Coronavirus Pandemic (COVID-19), dedicated to assessing the effects of this pandemic.

The researchers analysed the effects of isolation in male mice models suffering from advanced stages of Alzheimer's disease through a series of behavioural tests, which could be compared to several areas found in elderly residence homes. They compared these results with mice models of Alzheimer's that were not isolated, and with other healthy animal models undergoing a normal ageing process. The study was conducted with male mice because these are more affected by Covid-19 and are also the ones to show more deterioration of the neuro-immuno-endocrine system and worse survival conditions when suffering dementia.

The main findings demonstrate that isolation exacerbates hyperactivity up to twice as normal in mice with Alzheimer's disease, and also causes the appearance of strange behaviours. This increase was demonstrated consistently in the gross motor skills, related to the movement of arms, legs, feet or the entire body. However, it also affected fine motor skills, small movements made by hands, wrists, fingers, toes, lips and tongue. The isolated animals showed emotional patterns comparable to anxiety and changes in their stress management strategies.

"The results are concerning, given that anxiety is one of the main neuropsychiatric symptoms associated with dementia, which produces a large burden on the caregiver and, in some cases, makes clinical management a challenge", points out Aida Muntsant, first autor of the research, which is included as part of her PhD thesis.

Effects of isolation on memory

Researchers also analysed the effects of isolation on other neuropathological variables, and obtained different results. "Although the characteristic variables of the disorder, like taupathy, were not modified, some others such as asymmetric hippocampal atrophy increased with isolation. This dysfunction was recently described in human patients with dementia and modelled here for the first time with animal models of Alzheimer's disease. The finding is important, given that asymmetry has been linked to greater vulnerability to stress factors", states Lydia Giménez-Llort, Professor in Psychiatry and researcher at the INc directing the study.

The study also confirmed that the mice suffering from Alzheimer's disease lost body and renal mass, effects which also have been observed in Covid-19 patients, although the loss was greater with those in isolation. The loss in spleen mass, an important organ of the peripheral immune system, was only observed in isolated animals.

Rethinking isolation among the elderly

"Thinking of what the post-Covid-19 era will be like for the elderly implies a great deal of effort in redesigning all conditions of life, interventions in care and rehabilitation, and the management of forced solitude as part of new physical distancing measures. Therefore, it is necessary and urgent to estimate the impact these measures will have on the more vulnerable elderly population, such as those suffering from dementia", the researchers point out.

The study also highlights the need for personalised interventions adapted to the heterogeneous and complex clinical profile of people with dementia, and to consider how all of this affects the obligations of caregivers, whether they be professionals or members of the patient's family.
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The results of the study form part of Aida Muntsant's PhD thesis and are a product of the research led by Lydia Giménez-Llort, under the framework of the project ArrestAD H2020 Fet-OPEN-1-2016-2017-737390, led by Dulce Papy of the Paris-Est Créteil University, UPEC.

Universitat Autonoma de Barcelona

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