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Polysomnography (PSG) studies of sleep changes in Alzheimer’s disease (AD) have reported but not fully established the relationship between sleep disturbances and AD. To better detail this relationship, we conducted a systematic review and meta-analysis of reported PSG differences between AD patients and healthy controls. An electronic literature search was conducted in EMBASE, MEDLINE, All EBM databases, CINAHL, and PsycINFO inception to Mar 2021. Twenty-eight studies were identified for systematic review, 24 of which were used for meta-analysis. Meta-analyses revealed significant reductions in total sleep time, sleep efficiency, and percentage of slow-wave sleep (SWS) and rapid eye movement (REM) sleep, and increases in sleep latency, wake time after sleep onset, number of awakenings, and REM latency in AD compared to controls. Importantly, both decreased SWS and REM were significantly associated with the severity of cognitive impairment in AD patients. Alterations in electroencephalogram (EEG) frequency components and sleep spindles were also observed in AD, although the supporting evidence for these changes was limited. Sleep in AD is compromised with increased measures of wake and decreased TST, SWS, and REM sleep relative to controls. AD-related reductions in SWS and REM sleep correlate with the degree of cognitive impairment. Alterations in sleep EEG frequency components such as sleep spindles may be possible biomarkers with relevance for diagnosing AD although their sensitivity and specificity remain to be clearly delineated. AD-related sleep changes are potential targets for early therapeutic intervention aimed at improving sleep and slowing cognitive decline.

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We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid cell populations. The number of CD206+ brain perivascular macrophages (PVMs) was significantly greater in uninfected infants than in uninfected adults and was markedly lower in SIV-infected infants while microglia numbers were unchanged across groups. CD206+ PVMs, which proliferate after infection in SIVinfected adults, did not undergo proliferation in infants. While virtually all CD206+ cells in adults are also CD163+, infants have a distinct CD206 single-positive population in addition to the double-positive population commonly seen in adults. Notably, we found that more than 60% of these unique CD206+CD163− PVMs in SIV-infected infants were positive for cleaved caspase-3, an indicator of apoptosis, and that nearly 100% of this subset were concomitantly positive for the necroptosis marker receptorinteracting protein kinase-3 (RIP3). These findings show that distinct subpopulations of PVMs found in infants undergo programmed cell death instead of proliferation following SIV infection, which may lead to the absence of PVM-dependent SIVE and the limited size of the virus reservoir in the infant brain.

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Objective Common methodologies for treating depressive symptoms have demonstrated decreased efficacy among individuals with impaired cognitive functioning. While transcranial magnetic stimulation (TMS) has been approved to treat major depressive disorder, few studies have analyzed the ability of TMS to treat depressive symptoms among individuals with cognitive impairments. The present study had two objectives: to determine whether low-frequency TMS (LF-TMS) might demonstrate efficacy in treating depressive symptoms among individuals with impaired cognitive functioning; and to determine whether LF-TMS might improve neurocognitive functioning above and beyond depressive symptom improvements. Methods Data were derived from a pre-existing database at Eastern Virginia Medical School. Fifty-three (N=53) participants completed LF-TMS treatment. The Beck Depression Inventory II (BDI-II) and CNS Vital Signs (CNS-VS) neurocognitive assessment were administered at multiple time points throughout treatment. Participants were classified as impaired cognitive functioning or average cognitive functioning based on baseline CNS-VS scores. Data were analyzed using restricted maximum likelihood (REML) measures-within-persons longitudinal hierarchical linear modeling (HLM) with time-varying covariates. Results LF-TMS produced significant reductions in depressive symptoms for individuals in both cognitive functioning groups; however, a significant group-by-time interaction indicates differential effects between these two groups. Low-frequency TMS produced significant improvements in three neurocognitive domains above and beyond improvements in depressive symptoms; however, the reliability of these changes may be questionable. Conclusions This study adds to the growing body of empirical findings for LF-TMS treatment in improving neurocognitive functioning above and beyond other treatment-related effects.

Creutzfeldt–Jakob disease (CJD) is a rare form of rapidly progressive, neurodegenerative disease that results from the misfolding and accumulation of an aberrant, disease-associated prion protein (PrPD). CJD affects 1–1.5 cases per million per year with the sporadic-type accounting for an estimated 85% of these cases. Sporadic CJD (sCJD) is further subdivided into five subtypes based on genetic polymorphisms; the rarest subtype, sCJDVV1, occurs at a rate of 1 case per one-hundredth million population per year. Clinical characteristics of the sCJDVV1 subtype have been reported to show, early age of onset (44 years), average disease duration of 21 months, absent PSWCs on electroencephalography (EEG), and MRI hyperintensities in the cerebral cortex with usual negative signal in the basal ganglia or thalamus. We present a case of the sCJDVV1 subtype with uncommon features. Contrary to current data on sCJDVV1, our patient presented with an unusual age at onset (61 years) and longer disease duration (32 months). The highly sensitive and specific real-time quaking-induced conversion (RT-QuIC) assay was negative. Presenting clinical symptoms included paranoid thoughts and agitation, rapidly progressive memory decline, prosopagnosia, and late development of myoclonus and mutism. Other findings showed positive antithyroid peroxidase antibodies (anti-TPO), and absent PSWCs on EEG. High-dose steroid therapy treatment was administered based on positive anti-TPO findings, which failed to elicit any improvement and the patient continued to decline. To our knowledge, only four cases with the sCJDVV1 subtype, including our patient, have been reported to have a negative result on RT-QuIC. This may suggest varied sensitivity across sCJD subtypes. However, given the rarity of our patient's subtype, and the relatively novel RT-QuIC, current data are based on a small number of cases and larger cohorts of confirmed VV1 cases with RT-QuIC testing need to be reported.