Somatosensory dysfunction is masked by variable cognitive deficits across patients on the Alzheimer's disease spectrum

Abstract

Background: Alzheimer's disease (AD) is generally thought to spare primary sensory function; however, such interpretations have drawn from a literature that has rarely taken into account the variable cognitive declines seen in patients with AD. As these cognitive domains are now known to modulate cortical somatosensory processing, it remains possible that abnormalities in somatosensory function in patients with AD have been suppressed by neuropsychological variability in previous research. Methods: In this study, we combine magnetoencephalographic (MEG) brain imaging during a paired-pulse somatosensory gating task with an extensive battery of neuropsychological tests to investigate the influence of cognitive variability on estimated differences in somatosensory function between biomarker-confirmed patients on the AD spectrum and cognitively-normal older adults. Findings: We show that patients on the AD spectrum exhibit largely non-significant differences in somatosensory function when cognitive variability is not considered (p-value range: .020À.842). However, once attention and processing speed abilities are considered, robust differences in gamma-frequency somatosensory response amplitude (p < .001) and gating (p = .004) emerge, accompanied by significant statistical suppression effects. Interpretation: These findings suggest that patients with AD exhibit insults to functional somatosensory processing in primary sensory cortices, but these effects are masked by variability in cognitive decline across individuals.

A tool for mapping microglial morphology, morphOMICs, reveals brain-region and sex-dependent phenotypes

“…To address how morphological phenotypes differ between microglia across brain regions, we immunostained the adult C57BL/6J mouse brain with the allograft inflammatory factor 1 (Aif1/Iba1) 16 for both sexes with at least biological triplicates. Then, we traced 9,997 cells and generated a library of 3D microglial skeletons from seven brain regions chosen to span the rostrocaudal axis with a preference for regions that are known to be affected in Alzheimer disease [17][18][19][20][21][22][23] : the olfactory bulb (OB mg ), frontal cortex (FC mg ), dentate gyrus of the hippocampus (DG mg ), primary somatosensory cortex (S1 mg ), substantia nigra (SN mg ), cochlear nucleus (CN mg ) and cerebellum (CB mg ; Fig. 1a).…”

Signatures of somatosensory cortical dysfunction in Alzheimer’s disease and HIV-associated neurocognitive disorder

“…To identify the impact of Alzheimer’s disease and HAND pathologies on somatosensory gating and be consistent with previous studies, 13 , 14 , 40 we computed the gating ratio (i.e. response to Stimulation 2 divided by the response to Stimulation 1) and ran a 3 × 1 ANOVA.…”

“… 82 , 83 Further, one recent study showed that such gating deficits can be obscured by differences in neurocognitive function. 40 Interestingly, this latter study focused on somatosensory gating and involved patients across the Alzheimer’s disease spectrum (i.e. mild cognitive impairment (MCI) and mild Alzheimer’s disease).…”

“… 35 Sensory gating is generally understood as a bottom-up inhibitory process, and an extensive literature has shown robust gating of gamma-frequency oscillations. 13 , 15 , 36–39 While numerous studies have found aberrant auditory gating in Alzheimer’s disease, somatosensory gating has been examined only once in Alzheimer’s disease 40 and only a handful of times in HAND. 13–15 To the best of our knowledge, no study to date has compared somatosensory gating deficits in participants with HAND versus those with Alzheimer’s disease.…”

Retrospective comparison of motor and somatosensory MEG mapping—Considerations for better clinical applications

“…For somatosensory paradigms, epochs were of 0.3 s duration, with 0.0 s defined as stimulation onset and the baseline being the −0.05 to 0.0 s window. Epochs containing artifacts were excluded using a fixed threshold method (i.e., based on artifactual neural amplitude values), supplemented with visual inspection ( Christopher-Hayes et al, 2021 , Spooner et al, 2021a , Wiesman et al, 2021 ). Artifact-free epochs were time-domain averaged with respect to movement or stimulation onset.…”