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

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 somato-sensory 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 somato-sensory function when cognitive variability is not considered (p-value range: .020-.842). However, once attention and processing speed abilities are considered, robust differences in gamma-frequency somatosensory response amplitude (p \u3c .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

Piecing it together: atrophy profiles of hippocampal subfields relate to cognitive impairment along the Alzheimer’s disease spectrum

IntroductionPeople with Alzheimer’s disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls.MethodsParticipants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes.ResultsOur results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory.DiscussionThese findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum

A multicenter assessment of interreader reliability of LI-RADS version 2018 for MRI and CT

Background: Various limitations have impacted research evaluating reader agreement for Liver Imaging-Reporting and Data System (LI-RADS). Purpose: To assess reader agreement of LI-RADS in an international multi-center, multireader setting using scrollable images. Materials and Methods: This retrospective study used de-identified clinical multiphase CT and MRI examinations and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 – August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS v2018 category was computed as a re-scored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1/2, LR-3, LR-4, LR-5/M/tumor in vein) was computed using intra-class correlation coefficients (ICC). Agreement was also computed for dichotomized malignancy (LR-4/LR5/LR-M/LR-tumor in vein), LR-5, and LR-M. Agreement was compared between researchversus-research reads and research-versus-clinical reads. Results: 484 patients (mean age, 62 years ±10 [SD]; 156 women; 93 CT, 391 MRI) were included. ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.62, 0.74), 0.63 (95% CI: 0.56, 0.71), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs. 0.62, P = .03) and for dichotomized malignancy (ICC, 0.63 vs. 0.53, P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion: There was moderate agreement for Liver Imaging-Reporting and Data System v2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study

Rapid Effects of Hearing Song on Catecholaminergic Activity in the Songbird Auditory Pathway

Catecholaminergic (CA) neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH), a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses

Movement-related beta and gamma oscillations indicate parallels and disparities between Alzheimer's disease and HIV-associated neurocognitive disorder

People with HIV (PWH) often develop HIV-related neurological impairments known as HIV-associated neurocognitive disorder (HAND), but cognitive dysfunction in older PWH may also be due to age-related disorders such as Alzheimer's disease (AD). Discerning these two conditions is challenging since the specific neural characteristics are not well understood and limited studies have probed HAND and AD spectrum (ADS) directly. We examined the neural dynamics underlying motor processing during cognitive interference using magnetoencephalography (MEG) in 22 biomarker-confirmed patients on the ADS, 22 older participants diagnosed with HAND, and 30 healthy aging controls. MEG data were transformed into the time-frequency domain to examine movement-related oscillatory activity and the impact of cognitive interference on distinct stages of motor programming. Both cognitively impaired groups (ADS/HAND) performed significantly worse on the task (e.g., less accurate and slower reaction time) and exhibited reductions in frontal and cerebellar beta and parietal gamma activity relative to controls. Disease-specific aberrations were also detected such that those with HAND exhibited weaker gamma interference effects than those on the ADS in frontoparietal and motor areas. Additionally, temporally distinct beta interference effects were identified, with ADS participants exhibiting stronger beta interference activity in the temporal cortex during motor planning, along with weaker beta interference oscillations dispersed across frontoparietal and cerebellar cortices during movement execution relative to those with HAND. These results indicate both overlapping and distinct neurophysiological aberrations in those with ADS disorders or HAND in key motor and top-down cognitive processing regions during cognitive interference and provide new evidence for distinct neuropathology

Sleep quality differentially modulates neural oscillations and proteinopathy in Alzheimer's diseaseResearch in context

Summary: Background: Alterations in resting-state neural activity have been reported in people with sleep disruptions and in patients with Alzheimer's disease, but the direct impact of sleep quality on Alzheimer's disease-related neurophysiological aberrations is unclear. Methods: We collected cross-sectional resting-state magnetoencephalography and extensive neuropsychological and clinical data from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal older control participants. Sleep efficiency was quantified using the Pittsburgh Sleep Quality Index. Findings: Neural activity in the delta frequency range was differentially affected by poor sleep in patients on the Alzheimer's disease spectrum. Such neural changes were related to processing speed abilities and regional amyloid accumulation, and these associations were mediated and moderated, respectively, by sleep quality. Interpretation: Together, our results point to a mechanistic role for sleep disturbances in the widely reported neurophysiological aberrations seen in patients on the Alzheimer's disease spectrum, with implications for basic research and clinical intervention. Funding: National Institutes of Health, USA