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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.