Posted 07.19.2017 | by AMRA

Alzheimer’s Disease is a progressive brain disease affecting some five million older Americans. Given the profound personal, social, and economic costs of this disease, scientists are seeking ways to prevent its occurrence and progression. One avenue of investigation involves a protein called Repressor Element 1-Silencing Transcription Factor or REST. REST plays an important role in helping developing cells differentiate as neurons and protects aging brain cells from stress and toxicity.

People with Alzheimer’s have low REST levels, while older adults who retain their cognitive function well into their 90s and 100s have high REST levels. Also, older adults who show neurological changes typical of Alzheimer’s do not progress to show behavioral signs of the disease if their REST levels remain high.

Can raising REST levels reduce the risk for Alzheimer’s? Ashton et al. [Translational Psychiatry] explored this question using a new method for measuring REST in blood plasma. First they investigated whether this new REST measure in blood could discriminate between different levels of Alzheimer’s risk. Second, they studied whether Mindfulness-Based Stress Reduction (MBSR) improved REST levels in a population at risk for potentially developing Alzheimer’s.

The first study compared plasma REST levels in three groups of older (65 years or older) adults: 65 adults with Alzheimer’s, 65 adults with mild cognitive impairment, and 65 healthy adults. There was a significant difference between the Alzheimer’s group and both the healthy and mildly cognitively impaired groups. Mean REST levels were lowest for Alzheimer’s patients (112 pg mL-1) and highest for healthy controls (199 pg mL-1), with mildly cognitive impaired patients measuring in between (194 pg mL-1). Those mildly cognitive impaired who remained stable over time had higher REST levels (208 pg mL-1) than those who eventually progressed to Alzheimer’s diagnosis (180 pg mL-1).

The group with Alzheimer’s underwent magnetic resonance imaging (MRI) as well as testing for levels of 25 different plasma proteins known to be associated with cognitive decline and progression to Alzheimer’s. Higher REST levels were significantly correlated with increased hippocampal (r = .24), entorhinal cortex (r = .30), and whole brain (r = .21) volume as well as with four of the plasma markers (BDNF, NSE, PAI-1, and RANTES) associated with cognitive decline. BDNF plays a neuroprotective role and RANTES is involved in the immune response, whereas NSE is associated with neuronal injury and PAI-1 with aging, anxiety, and depression.

The second study included 81 older adults (65 years or older) who were either depressed or anxious and who reported subjective symptoms of cognitive impairment and were thus considered to be at risk for Alzheimer’s. They were randomly assigned to either an 8-week MBSR program, or an 8-week health education control group emphasizing factors such as healthy eating and medication management.

All participants were assessed at baseline and after intervention for plasma REST levels, plasma markers associated with cognitive decline, measures of short-term and delayed memory and executive function, and measures of anxiety, depression, and worry.

MBSR and control participants had significantly different REST levels at baseline, but not after the intervention. This was due to a 39 pg mL-1 REST increase in MBSR participants which was not matched by a similar rise in control participants.

Increased REST levels in MBSR and controls were significantly correlated with decreased depression and anxiety, but not with changes in cognitive functions or worry. REST levels at baseline were significantly positively correlated with three of the plasma proteins associated with cognitive decline (BDNF, RANTES, and PAI-1), but none of these markers changed significantly from baseline to post-intervention.

The study shows that plasma REST levels are associated with Alzheimer’s and mild cognitive impairment, and that REST levels can be increased through mindfulness training with concomitant improvements in depression and anxiety. Longer-term studies are needed to discover the degree to which MBSR-increased REST levels persist over time, and whether they can play a role in the prevention of Alzheimer’s.

Reference:

Ashton, N. J., Hye, A., Leckey, C. A., Jones, A. R., Gardner, A., Elliott, C., . . . Marchant, N. L. (2017). Plasma REST: A novel candidate biomarker of alzheimer’s disease is modified by psychological intervention in an at-risk population. Translational Psychiatry, 7(6), e1148.

[Link to abstract]