Association Between Types of Loneliness and Risks of Functional Disability in Older Men and Women: A Prospective Analysis

ObjectiveTo examine the association between types of loneliness (transient, incident, and chronic) and the risk of functional disability.MethodsData were from the Health and Retirement Study 2006/2008-2016/2018. A total of 7,148 adults aged ≥50 was included. Functional status was measured by activities of daily living (ADL) and instrumental activities of daily living (IADL). Loneliness was assessed using the 3-item UCLA Loneliness Scale. We defined loneliness as no/transient/incident/chronic loneliness based on the pattern and duration of loneliness across 2006/2008 and 2010/2012. We applied multivariate Cox proportional hazard models with the new-onset ADL/IADL disability as outcome.ResultsOverall, 69.3% respondents showed no loneliness; while 10.3%, 8.9%, and 11.5% showed transient, incident, and chronic loneliness, respectively. A total of 1,298 (18.16%) and 1,260 (17.63%) functionally normal respondents developed ADL and IADL disability during 36,294 person-years of follow-up, respectively. After adjusting for socio-demographic, behavioral, and health factors, chronic loneliness was associated with higher risks of ADL (hazard ratio [HR] = 1.37, 95% confidence interval [CI] = 1.16–1.63, p <0.001, χ² = 3.60, degree of freedom [df] = 1) and IADL disability (HR = 1.25, 95% CI = 1.09–1.44, p = 0.002, χ² = 3.17, df = 1) compared to no loneliness. By contrast, no significant associations between transient loneliness and ADL (HR = 1.17, 95% CI = 0.88–1.57, p = 0.273, χ² = 1.10, df = 1) or IADL disability (HR = 1.16, 95% CI = 0.97–1.39, p = 0.112, χ² = 1.59, df = 1) were found. Chronic loneliness was not associated with the risk of IADL disability in men (HR = 1.13, 95% CI = 0.91–1.40, p = 0.263, χ² = 1.12, df = 1).ConclusionChronic loneliness, rather than transient loneliness, is an independent risk factor for functional disability in middle-aged and older adults, especially for women.     

Accounting for functional loss in Alzheimer's disease and dementia with Lewy bodies: Beyond cognition

BackgroundThe relative contributions of cognitive, motor, and behavioral deficits to the impairment of physical or instrumental activities of daily living (ADLs) may differ in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).MethodsMultiple linear regression analyses were used to identify the amount of variability in physical self-maintenance and instrumental ADL ratings predicted by cognitive, motor, and behavioral indices separately for patients with autopsy-diagnosed DLB (n = 39) or AD (n = 39).ResultsMotor dysfunction accounted for significant variance in physical ADLs in DLB (R² change = 0.17), whereas behavioral (R² change = 0.23) and motor dysfunction (R² change = 0.13) accounted for significant variance in AD. Motor (R² change = 0.32) and cognitive (R² change = 0.10) dysfunction accounted for significant variance in instrumental ADLs in DLB, whereas cognitive (R² change = 0.36) and behavioral (R² change = 0.12) dysfunction accounted for significant variance in AD.ConclusionsCognitive, motor, and behavioral deficits contribute differently to ADL changes in DLB and AD. Thus, treatments designed to ameliorate a certain aspect of AD or DLB (e.g., cognitive dysfunction) may have a larger impact on everyday functioning in one disorder than the other.     

Diffusion imaging in dementia with Lewy bodies: Associations with amyloid burden,atrophy, vascular factors and clinical features

IntroductionWhite matter disruption in dementia has been linked to a variety of factors including vascular disease and cortical pathology. We aimed to examine the relationship between white matter changes on diffusion tensor imaging (DTI) in DLB and factors including vascular disease, structural atrophy and amyloid burden.MethodsParticipants with DLB (n = 29), Alzheimer's disease (AD, n = 17) and healthy controls (n = 20) had clinical and neuropsychological assessments followed by structural and diffusion tensor 3T MRI and ¹⁸F-Florbetapir PET-CT imaging. Voxelwise statistical analysis of white matter fractional anisotropy (FA) and mean diffusivity (MD) was carried out using Tract-Based Spatial Statistics with family-wise error correction (p < 0.05).ResultsDLB and AD groups demonstrated widespread increased MD and decreased FA when compared with controls. There were no differences between the DLB and AD groups. In DLB, increased MD and decreased FA correlated with decreased grey matter and hippocampal volumes as well as vascular disease. There was no correlation with cortical florbetapir SUVR. The relationship between DTI changes and grey matter/hippocampal volumes remained after including Cumulative Illness Rating Scale-Geriatric vascular score as a covariate.ConclusionsWidespread disruption of white matter tracts is present in DLB and is associated with vascular disease, reduced hippocampal volume and reduced grey matter volume, but not with cortical amyloid deposition. The mechanism behind the correlation observed between hippocampal volume and white matter tract disruption should be investigated in future cohorts using tau imaging, as hippocampal atrophy has been shown to correlate with tau deposition in DLB.     

Abnormalities of resting-state EEG in patients with prodromal and overt dementia with Lewy bodies: Relation to clinical symptoms

ObjectiveHere we tested if cortical sources of resting state electroencephalographic (rsEEG) rhythms may differ in sub-groups of patients with prodromal and overt dementia with Lewy bodies (DLB) as a function of relevant clinical symptoms.MethodsWe extracted clinical, demographic and rsEEG datasets in matched DLB patients (N = 60) and control Alzheimer’s disease (AD, N = 60) and healthy elderly (Nold, N = 60) seniors from our international database. The eLORETA freeware was used to estimate cortical rsEEG sources.ResultsAs compared to the Nold group, the DLB and AD groups generally exhibited greater spatially distributed delta source activities (DLB > AD) and lower alpha source activities posteriorly (AD > DLB). As compared to the DLB “controls”, the DLB patients with (1) rapid eye movement (REM) sleep behavior disorders showed lower central alpha source activities (p < 0.005); (2) greater cognitive deficits exhibited higher parietal and central theta source activities as well as higher central, parietal, and occipital alpha source activities (p < 0.01); (3) visual hallucinations pointed to greater parietal delta source activities (p < 0.005).ConclusionsRelevant clinical features were associated with abnormalities in spatial and frequency features of rsEEG source activities in DLB patients.SignificanceThose features may be used as neurophysiological surrogate endpoints of clinical symptoms in DLB patients in future cross-validation prospective studies.     

Medial temporal lobe atrophy on MRI in dementia with Lewy bodies

OBJECTIVE: To investigate whether medial temporal lobe atrophy (MTA) on MRI is less frequent in dementia with Lewy bodies (DLB) compared with AD and vascular dementia (VaD), and to determine the diagnostic utility of MTA in the differential diagnosis of dementia. METHOD: Coronal T1-weighted 1.0-T MR images were acquired in patients with DLB (consensus criteria; n = 26; mean age, 75.9 years), AD (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association; n = 28; mean age, 77.4 years), VaD (National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences; n = 24; mean age, 76.9 years), and normal control subjects (n = 26; mean age, 76.2 years). Cognitive function was assessed using the Cambridge Cognitive Examination (CAMCOG), and MTA was rated visually using a standardized scale. RESULTS: MTA was more frequent and severe in all dementia groups compared with control subjects (AD, 100%; VaD, 88%; DLB, 62%; control subjects, 4%; p < 0.001). Comparing dementia groups, MTA scores were significantly lower in DLB than AD (p = 0.002), with a trend toward less atrophy in DLB compared with VaD (p = 0.07). The absence of MTA had a specificity of 100% and 88% for separating DLB from AD and VaD respectively, and a sensitivity of 38%. In patients with DLB, MTA increased with age (r = 0.58, p = 0.002), and in all dementia patients MTA correlated with memory impairment (combined memory score, r = -0.34, p = 0.003) but not total CAMCOG score or other subscales. CONCLUSION: Patients with DLB have significantly greater MTA than control subjects but significantly less than those with AD. The authors confirmed that the presence of MTA is useful in detecting AD but less useful in differentiating between dementias. However, in the differentiation of DLB from AD and VaD, the absence of MTA is highly suggestive of a diagnosis of DLB.     

Polymorphisms in PDLIM5 gene are associated with alcohol dependence,type 2 diabetes,and hypertension

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in alcohol dependence (AD), bipolar disorder, and major depressive disorder; however, no study has identified shared genetic variants within PDLIM5 gene among AD, type 2 diabetes (T2D), and hypertension. This study investigated the association of 72 single nucleotide polymorphism (SNPs) with AD (1066 AD cases and 1278 controls) in the Study of Addiction - Genetics and Environment (SAGE) sample and 47 SNPs with T2D (878 cases and 2686 non-diabetic) and hypertension (825 cases and 2739 non-hypertensive) in the Marshfield sample. Multiple logistic regression models in PLINK software were used to examine the associations of genetic variants with AD, T2D, and hypertension and SNP x alcohol consumption interactions for T2D and hypertension. Twenty-five SNPs were associated with AD in the SAGE sample (p < 0.05); rs1048627 showed the strongest association with AD (p = 5.53 × 10⁻⁴). Of the 25 SNPs, 5 SNPs showed associations with both AD in the SAGE sample and T2D in the Marshfield sample (top SNP rs11097432 with p = 0.00107 for T2D and p = 0.0483 for AD) while 6 SNPs showed associations with both AD in the SAGE sample and hypertension in the Marshfield sample (top SNP rs12500426 with p = 0.0119 for hypertension and p = 1.51 × 10⁻³ for AD). SNP (rs6532496) showed significant interaction with alcohol consumption for hypertension. Our results showed that several genetic variants in PDLIM5 gene influence AD, T2D and hypertension. These findings offer the potential for new insights into the pathogenesis of AD, T2D, and hypertension.     

Low soluble amyloid-β 42 is associated with smaller brain volume in Parkinson's disease

IntroductionWe sought to examine whether levels of soluble alpha-synuclein (α‐syn), amyloid-beta (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau), as measured in cerebrospinal fluid (CSF), are associated with changes in brain volume in Parkinson's disease.MethodsWe assessed the 4-year change in total brain volume (n = 99) and baseline CSF α‐syn, Aβ42, p-tau, and t-tau of Parkinson Progression Markers Initiative participants. We used linear mixed models to assess the longitudinal effect of baseline CSF biomarkers on total and regional brain volume and thickness as well as linear regression for cross-sectional analyses at baseline and year 2. All models were adjusted for age and gender; brain volume models also adjusted for baseline intracranial volume. Bonferroni correction was applied.ResultsThe 4-year change in total brain volume was −21.2 mm³ (95% confidence interval, −26.1, −16.3). There were no significant associations between the 4-year change in total brain volume and baseline levels of any CSF biomarker (all p-values > 0.05). On cross-sectional analyses, CSF Aβ42 was linearly associated with total brain volume at baseline (R² = 0.60, p = 0.0004) and at year 2 (R² = 0.66, p < 0.0001), with CSF Aβ42 < 1100 pg/ml, the threshold for brain amyloid pathology, associated with smaller total brain volume at baseline (p = 0.0010) and at year 2 (p = 0.0002). CSF α‐syn was linearly associated with total brain volume at baseline (R² = 0.58, p = 0.0044) but not at year 2 (R² = 0.58, p = 0.1342).ConclusionReduction in soluble Aβ42 is associated with lower total brain volume in Parkinson's disease.     

Multivariate spatial covariance analysis of 99mTc-exametazime SPECT images in dementia with Lewy bodies and Alzheimer's disease: utility in differential diagnosis

We examined ^99mTc-exametazime brain blood flow single-photon emission computed tomography (SPECT) images using a spatial covariance analysis (SCA) approach to assess its diagnostic value in distinguishing dementia with Lewy bodies (DLB) from Alzheimer''s disease (AD). Voxel SCA was simultaneously applied to a set of preprocessed images (AD, n=40; DLB, n=26), generating a series of eigenimages representing common intercorrelated voxels in AD and DLB. Linear regression derived a spatial covariance pattern (SCP) that discriminated DLB from AD. To investigate the diagnostic value of the model SCP, the SCP was validated by applying it to a second, independent, AD and DLB cohort (AD, n=34; DLB, n=29). Mean SCP expressions differed between AD and DLB (F_1,64=36.2, P<0.001) with good diagnostic accuracy (receiver operating characteristic (ROC) curve area 0.87, sensitivity 81%, specificity 88%). Forward application of the model SCP to the independent cohort revealed similar differences between groups (F_1,61=38.4, P<0.001), also with good diagnostic accuracy (ROC 0.86, sensitivity 80%, specificity 80%). Multivariate analysis of blood flow SPECT data appears to be robust and shows good diagnostic accuracy in two independent cohorts for distinguishing DLB from AD.     

Psychological pathway to suicidal ideation among men who have sex with men in Shanghai,China: A structural equation model

We aimed to explore the relationships and develop an inter-theoretical model among psychological variables in the progression to suicidal ideation among men who have sex with men (MSM). A cross-sectional study was conducted among 547 MSM in four districts in Shanghai from March to May in 2014. Socio-demographic, psychological, and behavioral information of the participants was collected. A structural equation model (SEM)-Path Analysis was constructed to interpret the intricate relationships among various psychological variables. Suicidal ideation among MSM during the past year was 10.6%. The developed model agreed well with existing suicide models and had a good fit to the data (χ²/df = 2.497, comparative fit index = 0.983, root mean squared error of approximation = 0.052). Suicidal ideation was predicted by perceived defeat and entrapment (β = 0.21, p < 0.001), which was in turn predicted by temperament (β = 0.60, p < 0.001) and perceived social support (β = 0.34, p < 0.001). Perceived social support fully mediated the relationships among mood states, perceived social status, and perceived defeat and entrapment. MSM with certain types of temperament might be predisposed to a higher perception of defeat and entrapment. Perceived social support can effectively alleviate the negative appraisals and emotions and lower the risk for suicidal ideation among MSM.     

The diagnostic utility of cerebrospinal fluid alpha-synuclein analysis in dementia with Lewy bodies – A systematic review and meta-analysis

BackgroundDementia with Lewy Bodies (DLB) can be difficult to distinguish clinically from other dementias.ObjectiveTo investigate the diagnostic utility of CSF alpha-synuclein in differentiating between DLB and other dementias.MethodsElectronic databases were systematically searched for studies investigating reproducible alpha synuclein quantification methods. Random effects model was used to calculate weighted mean difference (WMD) and 95% confidence intervals between DLB and other groups.ResultsA total of 13 studies, comprising 2728 patients were included. Mean CSF alpha-synuclein concentration was significantly lower in DLB patients compared to those with Alzheimers disease (AD) [WMD ?0.24; 95% CI, ?0.45, ?0.03; p = 0.02]. No significant difference was found between patients with DLB compared to Parkinsons disease [WMD 0.05; 95% CI, ?0.17, 0.28; p = 0.65] or other neurodegenerative conditions.ConclusionCSF alpha synuclein may be of diagnostic use in differentiating between DLB and AD. We propose several recommendations to guide better design of future studies.     

Cerebrospinal fluid orexin in Alzheimer's disease: a systematic review and meta-analysis

Objective/backgroundA growing body of evidence suggests that sleep and Alzheimer's disease (AD) have a bi-directional relationship. Emerging research also suggests that orexin, a key neurotransmitter involved in sleep-wake regulation, may be altered in persons with AD, however results have not been consistent across prior studies. This investigation was conducted to both evaluate the aggregate literature to minimize the risk of bias and identify potential factors associated with heterogeneity across studies.MethodsSystematic review identified relevant investigations that compared cerebrospinal fluid orexin in persons with AD and controls. Meta-analysis (random effects model) compared effect size (Hedge's g) for orexin between AD and controls. Meta-regression was additionally performed for key variables of interest to evaluate potential causes of heterogeneity among studies.Results17 studies were identified that met inclusion/exclusion criteria. Evidence of publication bias was not identified. Non-significant increases in orexin were observed in AD relative to controls, with moderate to large heterogeneity among studies (Hedge's g = 0.20, p = 0.136, I² = 72.6%). Meta-regression demonstrated both year of publication (β = 0.055, p = 0.020) and effect size for phosphorylated tau in AD versus controls (β = 0.417, p = 0.031) were associated with differences in orexin.ConclusionsResults do not support broad differences in orexin in AD compared to controls, however, evolving diagnostic criteria may have affected findings across studies. Future research that examines orexin in AD over the longitudinal course of the disorder and explores potential links between phosphorylated tau and orexin are indicated.     

Genetic variants in the CPNE5 gene are associated with alcohol dependence and obesity in Caucasian populations

Alcohol addiction may increase the risk of obesity due to shared genetic components. The Copine V (CPNE5) gene is involved in Ca²⁺ binding and may play an important role in the development of the central nervous system. This study tested the genetic associations of 77 single-nucleotide polymorphisms (SNPs) within the CPNE5 gene with alcohol dependence (AD) and obesity using a Caucasian sample – The Study of Addiction – Genetics and Environment (SAGE) sample (1066 AD cases and 1278 non-AD controls, 422 obese cases and 1395 non-obese controls). The Marshfield sample (1442 obese cases and 2122 non-obese controls) was used for replication of obesity. Multiple logistic regression analysis was performed using the PLINK software. In the SAGE sample, we identified 10 SNPs associated with AD and 17 SNPs associated with obesity (p < 0.05). Interestingly, 6 SNPs (rs9986517, rs9470387, rs3213534, rs10456444, rs3752482, and rs9470386) were associated with both AD (OR = 0.77, 0.77, 0.83, 0.84, 0.79 and 1.14, respectively; p = 9.72 × 10⁻⁵, 1.1 × 10⁻⁴, 4.09 × 10⁻³, 5.26 × 10⁻³, 1.59 × 10⁻², and 3.81 × 10⁻², respectively) and obesity (OR = 0.77, 0.77, 0.78, 0.77, 0.68 and 1.18, respectively; p = 2.74 × 10⁻³, 2.69 × 10⁻³, 2.45 × 10⁻³, 1.01 × 10⁻³, 5.18 × 10⁻³ and 3.85 × 10⁻², respectively). In the Marshfield sample, rs3752480 was associated with obesity (p = 0.0379). In addition, four SNPs (rs9986517, rs10456444, rs7763347 and rs4714010) showed associations with obesity in the meta-analysis using both samples (p = 0.00493, 0.0274, 0.00346, and 0.0141, respectively). These findings provide the first evidence of common genetic variants in the CPNE5 gene influencing both the AD and obesity; and will serve as a resource for replication in other populations.     

Concomitant pathologies among a spectrum of parkinsonian disorders

IntroductionMany clinicopathological studies do not specify the presence of other pathologies located within the brain, so disease heterogeneity may be under appreciated.ObjectiveThe purpose of this study was to determine the frequencies of concomitant pathologies among parkinsonian disorders.MethodsData from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), an ongoing longitudinal clinical-neuropathological study, was used to analyze concomitant pathologies, including Alzheimer's disease (AD), argyrophilic grains (Arg), cerebral amyloid angiopathy (CAA), cerebral white matter rarefaction (CWMR) and overlap of each parkinsonian disorder in clinico-pathologically defined Parkinson's disease (PD; N = 140), dementia with Lewy bodies (DLB; N = 90), progressive supranuclear palsy (PSP; N = 64), multiple system atrophy (MSA; N = 6), corticobasal degeneration (CBD; N = 7); and normal elderly (controls; N = 166).ResultsOf the neuropathologically-confirmed PD cases, 38% had a concomitant diagnosis of AD, 9% PSP, 25% Arg, 44% CWMR, and 24% CAA. For DLB, 89% had AD, 1% PSP, 21% Arg, 51% CWMR, and 50% CAA. For PSP cases, 36% had AD, 20% PD, 1% DLB, 44% Arg, 52% CWMR and 25% CAA. Similar heterogeneity was seen for MSA and CBD cases. Many cases had more than one of the above additional diagnoses.ConclusionsThese data demonstrate a great deal of concomitant pathologies among different types of parkinsonian disorders; this may help explain the heterogeneity of clinical findings.     

DNA methylation changes at TREM2 intron 1 and TREM2 mRNA expression in patients with Alzheimer's disease

ObjectivesRecent genome-wide association studies revealed that Triggering receptor expressed on myeloid cells 2 (TREM2) was associated with Alzheimer's disease (AD) and other neurodegenerative diseases. We previously reported that TREM2 mRNA is highly expressed in leukocytes of AD patients compared to those in healthy controls. However, the mechanism of TREM2 expression change is still not known. In this study, we examined the involvement of the DNA methylation status of TREM2 in its high gene expression.Materials and methodsFifty AD subjects and age- and sex-matched control subjects were recruited (25 males, 25 females; 79.9 ± 5.27 and 79.4 ± 3.92 years old, respectively). TREM2 mRNA expression and the percentage of DNA methylation at four CpG sites in intron 1 of TREM2 were studied using their peripheral leukocytes.ResultsWe confirmed that TREM2 mRNA expression in leukocytes was significantly higher in AD patients than in controls (p = 0.007). The percentage methylation at three CpG sites in TREM2 intron 1 was significantly lower in AD subjects than in control: CpG1, 9.4 ± 3.2 vs 11.9 ± 4.0 (p = 0.001); CpG2, 15.4 ± 4.9 vs 19.1 ± 4.8 (p = 0.001); CpG3, 20.8 ± 5.5 vs 25.5 ± 5.4 (p < 0.001); and the average percentage methylation of all CpG sites: 13.5 ± 3.7 vs 16.1 ± 3.8 (p = 0.002), respectively. In addition, there were significant negative correlations between TREM2 mRNA expression and the percentage DNA methylation of each of CpG sites (CpG1, r = −0.416, p < 0.001; CpG2, r = −0.510, p < 0.001; CpG3, r = −0.504, p < 0.001; CpG4, r = −0.356, p < 0.001).ConclusionsLower DNA methylation at TREM2 intron 1 caused higher TREM2 mRNA expression in the leukocytes of AD subjects versus controls and may be a biomarker for AD.     

Development and validation of the hypersomnia-specific beliefs scale

Objective/BackgroundPatients with Central hypersomnia, especially Narcolepsy type 1 and Idiopathic Hypersomnia (NT1 and IHS) often have psychological frustration in their daily lives. We aimed to develop the first scale of hypersomnia-specific beliefs (HSB).Patients/methodsWe developed the HSB scale consisting of three factors (“aversion toward doze”, “hypersensitivity toward others” reactions about my doze”, and “sense of defeat caused by doze”) with 12 items through interviews to 11 patients with NT1 and IHS. Validity and reliability of the HSB were evaluated cross-sectionally with 166 patients with NT1 and IHS and 375 controls. Simultaneously, scores of patient health questionnaire −2(PHQ-2), mini-Social Phobia Inventory (mini-SPIN), and Epworth Sleepiness Scale (ESS) were obtained.ResultsThis 3-factor model had enough fitness (χ2 = 60.25, df = 51, p = 0.18, TLI = 0.99, CFI = 0.99, RMSEA = 0.03), Cronbach's α coefficient being 0.90. The intraclass correlation coefficient was 0.76. Also, the area under the receiver operating characteristic curve (AUC = 0.88) confirmed good discrimination ability. A cut-off score of 38 resulted in a sensitivity of 90% and a specificity of 75%. Multiple linear regression analyses showed that these scales were independently associated with the HSB score; the PHQ-2 (β = 0.24, p = 0.002), mini-SPIN (β = 0.29, p < 0.001) and ESS (β = 0.15, p = 0.048).ConclusionsOur data suggest that the HSB scale measured beliefs in NT1 and IHS patients with good validity, reliability, and discrimination ability. The HSB scale assesses the negative beliefs specific to patents with NT1 and IHS. This scale could be applied to the development of novel psychotherapeutic approach to patients with NT1 and IHS.     

Shortened telomere length in patients with depression: A meta-analytic study

BackgroundAccelerated telomere shortening is associated with stress-related cell damage and aging. Patients with depression have been shown to have shortened life expectancy and to be associated with multiple age-related systemic diseases. Previous studies have examined leukocyte telomere length (LTL) in patients with depression, but have shown inconsistent results.MethodsWe conducted meta-analyses by pooling relevant results strictly from all eligible case–control studies for cross-sectional comparison of LTL between depressive patients and control subjects (16 studies involving 7207 subjects). The effect sizes (shown as Hedges' g) of each individual study were synthesized by using a random effects model.ResultsOur analysis revealed telomere length is significantly shorter in subjects with depression in comparison to healthy controls (Hedges' g = −0.42, p = 1 × 10⁻⁵, corresponding to r = −0.21). Significant heterogeneity among studies examining LTL in subjects with depression was found (Q = 116.07, df = 16, I² = 86.21%, p < 1 × 10⁻⁸), which can possibly be explained by methods used in measuring telomere length (Q = 18.42, df = 2, p = 1 × 10⁻⁴). There was no significant publication bias, nor moderating effect of age, female percentage, or illness duration of depression on synthesized results.ConclusionsOur results support the hypothesis that depression is associated with accelerated cell aging. Future studies are required to clarify whether the association is mediated through environmental stress, and whether effective treatment can halt cell aging.     

Sex differences within symptom subtypes of mild obstructive sleep apnea

ObjectivesPrior studies have identified symptom subtypes of moderate to severe (AHI >15) obstructive sleep apnea (OSA). They have not yet been consistently examined in those with mild OSA (AHI 5–15 events/hour). This is important as women are more likely than men to present with mild OSA and may present with different OSA symptoms. The objectives of this study were to determine 1) symptom subtypes in mild OSA and 2) if there are sex differences in the distribution of subtypes.MethodsThe sample included men (n = 921) and women (n = 797) with mild OSA, aged 39–90 years, evaluated with a single night of in–home polysomnography as part of the Sleep Heart Health Study. Latent class analysis determined symptom subtypes. Testing for sex differences relative to OSA severity and symptom subtype used chi-squared test for independence. Bonferroni corrected z-tests compared column proportions.ResultsSymptom subtypes of mild OSA were not significantly different than those identified in prior studies of moderate-severe OSA (p > 0.05): minimally symptomatic (36.4%), disturbed sleep (11.6%), moderately sleepy (37%), and excessively sleepy (15%), p > 0.05. Sex differences within the symptom subtypes were significant [χ²(df = 3) = 30.04, p < 0.001, Cramer's V = 0.132]. Relative to men, women were more likely to be in the disturbed sleep subtype (p < 0.05), and the excessively sleepy subtype (p < 0.05) while less likely to be in the moderately sleep (<0.05) subtype. Women and men were equally represented in the minimal symptoms subtype (p > 0.05).ConclusionsResults suggest symptom reporting among individuals with mild OSA differs as a function of sex. These data have important clinical implications for screening men and women for OSA.     

Resting EEG theta connectivity and alpha power to predict repetitive transcranial magnetic stimulation response in depression: A non-replication from the ICON-DB consortium

ObjectiveOur previous research showed high predictive accuracy at differentiating responders from non-responders to repetitive transcranial magnetic stimulation (rTMS) for depression using resting electroencephalography (EEG) and clinical data from baseline and one-week following treatment onset using a machine learning algorithm. In particular, theta (4–8 Hz) connectivity and alpha power (8–13 Hz) significantly differed between responders and non-responders. Independent replication is a necessary step before the application of potential predictors in clinical practice. This study attempted to replicate the results in an independent dataset.MethodsWe submitted baseline resting EEG data from an independent sample of participants who underwent rTMS treatment for depression (N = 193, 128 responders) (Krepel et al., 2018) to the same between group comparisons as our previous research (Bailey et al., 2019).ResultsOur previous results were not replicated, with no difference between responders and non-responders in theta connectivity (p = 0.250, Cohen’s d = 0.1786) nor alpha power (p = 0.357, η_p² = 0.005).ConclusionsThese results suggest that baseline resting EEG theta connectivity or alpha power are unlikely to be generalisable predictors of response to rTMS treatment for depression.SignificanceThese results highlight the importance of independent replication, data sharing and using large datasets in the prediction of response research.