Lobe‐specific changes in white matter volume and myelination following 6‐month 40 Hz gamma sensory stimulation in patients on the Alzheimer’s disease spectrum

Abstract

AbstractBackgroundAlthough morphometric changes in Alzheimer’s Disease (AD) occur both in gray and white matter, gray matter changes had been the primary focus of previous work. Recent studies have highlighted the importance of pathological changes in white matter and myelination in AD patients, including early changes to oligodendrocytes and transcription of myelin protein genes in the white matter prior to symptoms of cognitive decline, even in subjects with AD but without other neurological comorbidities (Ferrer et al., 2020). Since neuronal activities, particularly network oscillations have been shown to promote myelination, the present study examined how 40Hz gamma stimulation affected white matter volume and myelination in different cortical lobes in patients with AD.MethodData were obtained from the Overture trial (NCT03555281) in which treatment participants received daily, at‐home, 40Hz gamma sensory stimulation for six months, while placebo participants received sham stimulation (treatment‐to‐placebo ratio 2:1). Magnetic resonance imaging (MRI) data were collected at 1.5 Tesla at baseline, month 3, and month 6. MRI T1 images and T1w/T2w ratios were used to estimate volume (N = 38) and myelination (N = 36), respectively. Using Bayesian linear mixed effects modeling, we estimated white matter volume and myelination percent changes with respect to baseline. Treatment group results were reported in relation to the placebo group.ResultWith respect to the placebo group: In the left hemisphere, the treatment group exhibited reduced white matter atrophy in the frontal lobe (‐3.27±1.4, p = 0.0225), in the temporal lobe (‐3.9±1.76, p = 0.0306), in the parietal lobe (‐3.32±1.43, p = 0.0236), in the occipital lobe (‐4.1±1.72, p = 0.0195) and reduced demyelination in the frontal lobe (‐5.13±2.12, p = 0.0186), in the temporal lobe (‐5.33±2.42, p = 0.0321), in the parietal lobe (‐5.7±2.07 (p = 0.0079), in the occipital lobe (‐5.65±2.52, p = 0.0296). In the right hemisphere, the treatment group trended towards reduced white matter volume loss and demyelination in all lobes, however, demyelination was significantly reduced in the parietal lobe (‐4.48±2.09, p = 0.037), and in the occipital lobe (‐5.5±2.22, p = 0.0165).ConclusionWhite matter atrophy and demyelination were statistically significantly reduced in all lobes of the left hemisphere and trended towards reduction in the right hemisphere, demonstrating that 40Hz sensory stimulation can reduce the neurodegeneration associated with AD.