Dementia Risk in Posttraumatic Stress Disorder: the Relevance of Sleep-Related Abnormalities in Brain Structure, Amyloid, and Inflammation.

PURPOSE OF REVIEW: Posttraumatic stress disorder (PTSD) is associated with increased risk for dementia, yet mechanisms are poorly understood. RECENT FINDINGS: Recent literature suggests several potential mechanisms by which sleep impairments might contribute to the increased risk of dementia observed in PTSD. First, molecular, animal, and imaging studies indicate that sleep problems lead to cellular damage in brain structures crucial to learning and memory. Second, recent studies have shown that lack of sleep might precipitate the accumulation of harmful amyloid proteins. Finally, sleep and PTSD are associated with elevated inflammation, which, in turn, is associated with dementia, possibly via cytokine-mediated neural toxicity and reduced neurogenesis. A better understanding of these mechanisms may yield novel treatment approaches to reduce neurodegeneration in PTSD. The authors emphasize the importance of including sleep data in studies of PTSD and cognition and identify next steps.

Are hippocampal size differences in posttraumatic stress disorder mediated by sleep pathology?

Posttraumatic stress disorder (PTSD) is associated with smaller volumes of the hippocampus, as has been demonstrated by meta-analyses. Proposed mechanistic relationships are reviewed briefly, including the hypothesis that sleep disturbances mediate the effects of PTSD on hippocampal volume. Evidence for this includes findings that insomnia and restricted sleep are associated with changes in hippocampal cell regulation and impairments in cognition. We present results of a new study of 187 subjects in whom neither PTSD nor poor sleep was associated with lower hippocampal volume. We outline a broad research agenda centered on the hypothesis that sleep changes mediate the relationship between PTSD and hippocampal volume.

Pretreatment stabilization increases completion of trauma-focused evidence-based psychotherapies.

OBJECTIVE: Veterans with posttraumatic stress disorder (PTSD) initiate and complete cognitive processing therapy (CPT) and prolonged exposure (PE) at low rates within Veterans Health Administration (VHA) despite substantial dissemination and training. This study investigated how trauma-informed, skills-based treatment ("stabilization") administered before CPT and PE was related to initiation and completion of trauma-focused evidence-based psychotherapies (TF-EBPs). METHOD: Data were extracted from the VHA electronic medical record to identify veterans who initiated outpatient treatment in the PTSD Clinical Team (PCT) at a Veterans Affairs Health Care System. Treatment initiation was defined as three or more PCT visits with no prior PCT care for at least 18 months (N = 341). Before initiation of TF-EBP, veterans received either no stabilization or received individual and/or group stabilization. RESULTS: Twenty-eight percent of veterans without stabilization (n = 115) initiated TF-EBP, compared with 34% of veterans who completed individual-only stabilization (n = 82), and 10% of veterans who completed group-only stabilization (n = 29, p = .050). Compared with those with no stabilization, individual stabilization was associated with significantly higher TF-EBP completion (93% vs. 50%, p < .001). CPT completion was also significantly higher for veterans who received individual-only stabilization (90% vs. 43%, p = .001). Results for PE followed the same relationship, but did not reach significance (100% vs. 67%, p = .090). CONCLUSIONS: Findings suggest that individual stabilization may improve delivery of TF-EBPs in VHA settings by increasing TF-EBP completion without reducing initiation, while pretreatment with group-only stabilization may reduce initiation of TF-EBPs. Results inform how models of care can improve TF-EBP retention and completion among veterans with PTSD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association of Sleep and ß-Amyloid Pathology Among Older Cognitively Unimpaired Adults.

Importance: Disrupted sleep commonly occurs with progressing neurodegenerative disease. Large, well-characterized neuroimaging studies of cognitively unimpaired adults are warranted to clarify the magnitude and onset of the association between sleep and emerging ß-amyloid (Aß) pathology. Objective: To evaluate the associations between daytime and nighttime sleep duration with regional Aß pathology in older cognitively unimpaired adults. Design, Setting, and Participants: In this cross-sectional study, screening data were collected between April 1, 2014, and December 31, 2017, from healthy, cognitively unimpaired adults 65 to 85 years of age who underwent florbetapir F 18 positron emission tomography (PET), had APOE genotype information, scored between 25 and 30 on the Mini-Mental State Examination, and had a Clinical Dementia Rating of 0 for the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study. Data analysis was performed from December 1, 2019, to May 10, 2021. Exposures: Self-reported daytime and nighttime sleep duration. Main Outcomes and Measures: Regional Aß pathology, measured by florbetapir PET standardized uptake value ratio. Results: Amyloid PET and sleep duration information was acquired on 4425 cognitively unimpaired participants (mean [SD] age, 71.3 [4.7] years; 2628 [59.4%] female; 1509 [34.1%] tested Aß positive). Each additional hour of nighttime sleep was associated with a 0.005 reduction of global Aß standardized uptake value ratio (F1, 4419 = 5.0; P = .03), a 0.009 reduction of medial orbitofrontal Aß (F1, 4419 = 17.4; P < .001), and a 0.011 reduction of anterior cingulate Aß (F1, 4419 = 15.9; P < .001). When restricting analyses to participants who tested Aß negative, nighttime sleep was associated with a 0.006 reduction of medial orbitofrontal Aß (F1,2910 = 16.9; P < .001) and a 0.005 reduction of anterior cingulate Aß (F1,2910 = 7.6; P = .03). Daytime sleep was associated with a 0.013 increase of precuneus Aß (F1,2910 = 7.3; P = .03) and a 0.024 increase of posterior cingulate Aß (F1,2910 = 14.2; P = .001) in participants who tested Aß negative. Conclusions and Relevance: In this cross-sectional study, the increased risk of Aß deposition with reduced nighttime sleep duration occurred early, before cognitive impairment or significant Aß deposition. Daytime sleep may be associated with an increase in risk for early Aß accumulation and did not appear to be corrective for loss of nighttime sleep, demonstrating a circadian rhythm dependence of sleep in preventing Aß accumulation. Treatments that improve sleep may reduce early Aß accumulation and aid in delaying the onset of cognitive dysfunction associated with early Alzheimer disease.

Laws and Ethics Related to Emotional Support Animals.

The use of animals for therapeutic benefit is well-established. For example, for individuals with a disability such as blindness, trained service dogs can enhance the ability to live independently and participate fully in society. An emotional support animal (ESA) is an untrained animal that is used to support a person disabled by an emotional or mental disorder. For an animal to qualify as an ESA, a mental health or medical professional needs to write a letter saying that the animal is needed for the mental health of the person with the disability. This article describes the legal framework for service animals and ESAs, as well as the differences between them. We summarize information about the Americans with Disabilities Act, the Fair Housing Act, the Air Carrier Access Act, and other laws governing an individual's right to be accompanied by a support animal. We also summarize the clinical research on ESAs and argue that, although there are few studies on the clinical effectiveness of ESAs, a broader body of research indicates that animals may have positive clinical effects on medical and mental illness. Finally, we suggest there is a need for further research and provider education on ESAs.

Total Sleep Time Interacts With Age to Predict Cognitive Performance Among Adults.

STUDY OBJECTIVES: To investigate interactions between high and low amounts of sleep and other predictors of cognitive performance. METHODS: We used four cognitive tests to determine whether sleep time interacted with age, personal history of a memory problem, parental history of a memory problem, or personal concerns about memory and were associated with cognitive performance. Data were collected from an internet-based cohort study. We used an ordinary least squares regression with restricted cubic splines, controlling for demographic variables and comorbidities. RESULTS: We found significant nonlinear interactions between (1) total sleep time and age and (2) total sleep time and personal history of a memory problem and cognitive performance. Short and long sleep durations and self-reported memory complaints were associated with poorer performance on a test of attention and this was true to a greater degree in younger and older adults. A repeat analysis excluding subjects reporting dementia was significant only for the test of attention. CONCLUSIONS: These results extend existing data on sleep duration and cognition across the lifespan by combining in a single study the results from four specific cognitive tests, both younger and older adults, and four self-reported risk factors for cognitive impairment. Longitudinal studies with biomarkers should be undertaken to determine whether causal mechanisms, such as inflammation or amyloid buildup, account for these associations.

Infrared micro-spectroscopic studies of epithelial cells.

We report results from a study of human and canine mucosal cells, investigated by infrared micro-spectroscopy, and analyzed by methods of multivariate statistics. We demonstrate that the infrared spectra of individual cells are sensitive to the stage of maturation, and that a distinction between healthy and diseased cells will be possible. Since this report is written for an audience not familiar with infrared micro-spectroscopy, a short introduction into this field is presented along with a summary of principal component analysis.

Sleep and Cognitive Performance From Teens To Old Age: More Is Not Better.

Objectives: To determine the interaction of age and habitual sleep duration in predicting cognitive performance in a large sample of participants aged 15 to 89 years. Methods: This study is a cross-sectional analysis of performance data gathered between January 2012 and September 2013. First-time players (N = 512823) of three internet cognitive training games measuring processing speed, working memory, visuospatial memory, and arithmetic participated in the study. Results: Performance was based on a measure of speed and accuracy for each game. The relationship between performance and self-reported habitual sleep duration was examined in the sample as a whole and across 10-year age groups starting at age 15 and ending at 75 and older. Performance peaked at 7 h of sleep duration for all three games in the sample as a whole, and the decrements in performance for sleep durations greater than 7 h were either comparable or greater in the youngest as compared to the oldest age groups. Conclusions: These findings challenge the hypothesis that deteriorating cognitive performance with long sleep duration is driven by medical comorbidities associated with aging. Further, these data are consistent with an optimal dose model of sleep and suggest that the model for the homeostatic recovery of cognitive function as a function of sleep duration should incorporate a curvilinear decline with longer duration sleep, indicating that there may be a cost to increased sleep. Replication and further research is essential for clarifying the sleep duration-cognition relationship in youth and adults of all ages.

Infrared micro-spectroscopy of human cells: Causes for the spectral variance of oral mucosa (buccal) cells.

We discuss the causes contributing to the variance of the spectra of individual human epithelial cells. This aspect has largely been ignored in previous studies, but needs to be understood for diagnostic applications of infrared micro-spectroscopy. We attribute the spectral variance to Mie scattering, and to variations of nuclear contributions to the overall spectra caused by different nuclear size.

Cerebrospinal fluid α-synuclein and Lewy body-like symptoms in normal controls, mild cognitive impairment, and Alzheimer's disease.

BACKGROUND: Reduced cerebrospinal fluid (CSF) α-synuclein has been described in synucleinopathies, including dementia with Lewy bodies (DLB). Common symptoms of DLB include visual hallucinations and visuospatial and executive deficits. Co-occurrence of Lewy body pathology is common in Alzheimer's disease (AD) patients, but it is unknown if reduced CSF α-synuclein is associated with Lewy body-like symptomatology in AD. OBJECTIVE: Determine associations between CSF α-synuclein and Lewy body-like symptomatology. METHODS: We included 73 controls (NC), 121 mild cognitive impairment (MCI) patients, and 61 AD patients (median follow-up 3.5 years, range 0.6-7.8). We tested associations between baseline CSF α-synuclein and visual hallucinations and (longitudinal) cognition. Models were tested with and without co-varying for CSF total tau (T-tau), which is elevated in AD patients, and believed to reflect neurodegeneration. RESULTS: Hallucinations were reported in 20% of AD patients, 13% of MCI patients, and 8% of NC. In AD, low CSF α-synuclein was associated with hallucinations. When adjusting for CSF T-tau, low CSF α-synuclein was associated with accelerated decline of executive function (NC, MCI, and AD), memory (MCI and AD), and language (MCI). CONCLUSION: The associations of low CSF α-synuclein with hallucinations and poor executive function, which are hallmarks of DLB, indirectly suggest that this biomarker may reflect underlying synuclein pathology. The associations with memory and language in MCI and AD suggests either that reduced CSF α-synuclein also partly reflects global impaired neuronal/synaptic function, or that non-specific overall cognitive deterioration is accelerated in the presence of synuclein related pathology. The findings will require autopsy verification.

Associations between subjective sleep quality and brain volume in Gulf War veterans.

STUDY OBJECTIVES: To investigate whether subjective sleep quality is associated with brain volume independent of comorbid psychiatric conditions. DESIGN: Cross-sectional. SETTING: Department of Veterans Affairs (VA) Medical Center. PARTICIPANTS: One hundred forty-four Gulf War Veterans (mean age 45 years; range: 31-70 years; 14% female). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Total cortical, lobar gray matter, and hippocampal volumes were quantified from 1.5 Tesla magnetic resonance images using Freesurfer version 4.5. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regressions were used to determine the association of sleep quality with total and regional brain volumes. The global PSQI score was positively correlated with lifetime and current posttraumatic stress disorder (PTSD) and current depressive symptoms (P < 0.001) and was higher in veterans with Gulf War Illness, trauma exposure, and those using psychotropic medication (P ≤ 0.03). After adjusting for these comorbid variables, age, intracranial volume, and multiple comparisons, global PSQI was inversely associated with total cortical and frontal gray matter volume (adjusted P ≤ 0.03). Within the frontal lobe, total PSQI was inversely associated with the superior and middle frontal, orbitofrontal, anterior cingulate, and frontal pole volumes (adjusted P ≤ 0.02). Examination of the 3-factor structure of the PSQI revealed that the associations were driven by perceived sleep quality. CONCLUSIONS: Poorer subjective sleep quality was associated with reduced total cortical and regional frontal lobe volumes independent of comorbid psychiatric conditions. Future work will be needed to examine if effective treatment of disturbed sleep leads to improved structural and functional integrity of the frontal lobes.

Mie-type scattering and non-Beer-Lambert absorption behavior of human cells in infrared microspectroscopy.

We report infrared microspectral features of nuclei in a completely inactive and contracted (pyknotic) state, and of nuclei of actively dividing cells. For pyknotic nuclei, the very high local concentration of DNA leads to opaqueness of the chromatin and, consequently, the absence of DNA signals in the IR spectra of very small nuclei. However, these nuclei can be detected by their scattering properties, which can be described by the Mie theory of scattering from dielectric spheres. This scattering depends on the size of the nucleus; consequently, quite different scattering cross-sections are calculated and observed for pyknotic and mitotic nuclei.