The association between cannabis use and neuroimaging measures in older adults: findings from the UK biobank.

BACKGROUND: Cannabis use has increased in recent years. However, the long-term implications of cannabis use on brain health remain unknown. We explored the associations of cannabis use with volumetric brain magnetic resonance imaging (MRI) measures in dementia-free older adults. METHODS: This cross-sectional and longitudinal study included dementia-free participants of the UK Biobank aged ≥60 years. Linear regression models were used to evaluate the association of cannabis use and patterns of use with volumetric brain MRI measures. The association between cannabis use and change in brain MRI measures over time was also tested. All models were adjusted for potential confounders. RESULTS: The sample included 19,932 participants (mean age 68 ± 5 years, 48% men), 3,800 (19%) reported lifetime use of cannabis. Cannabis use was associated with smaller total, white, grey and peripheral cortical grey matter volumes (B = -6,690 ± 1,157; P < 0.001, B = -4,396 ± 766; P < 0.001, B = -2,140 ± 690; P = 0.002 and B = -2,451 ± 606; P < 0.001, respectively). Among cannabis users, longer duration of use was associated with smaller total brain, grey and cortical grey matter volumes (B = -7,878 ± 2,396; P = 0.001, B = -5,411 ± 1,430; P < 0.001, B = -5,396 ± 1,254; P < 0.001, respectively), and with increased white matter hyperintensity volume (B = 0.09 ± 0.03; P = 0.008). Additionally, current vs. former users (B = -10,432 ± 4,395; P = 0.020) and frequent versus non-frequent users (B = -2,274 ± 1,125; P = 0.043) had smaller grey and cortical grey matter volumes, respectively. No significant associations were observed between cannabis use and change in brain MRI measures. DISCUSSION: Our findings suggest that cannabis use, particularly longer duration and frequent use, may be related to smaller grey and white matter volumes in older ages, but not to late-life changes in these measures over time.

Unraveling the debate: Can the skin manifestations of SARS-CoV-2 infection and vaccination be explained by the reactivation of herpes virus?

Since the COVID-19 outbreak, there have been numerous reports concerning COVID-19 skin manifestations. Debate has ensued as to whether these lesions are unique or represent a form of viral reactivation. The aim of this research was to compare the incidence of herpetic skin lesions between a COVID-19 group, a Sars-CoV-2 mRNA vaccination group, and their respective controls, taking into account their Herpesviridae carrier status. To achieve this goal, the Maccabi Healthcare Services' database was scanned and cohorts of both verified COVID-19 and mRNA vaccinated patients were extracted and matched to random control groups. Patients with a documented occurrence of any Herpesviridae infection that occurred prior to the studied 'event' (i.e., COVID-19 or mRNA vaccination) were regarded as carriers of Herpesviridae. A COVID-19-related or vaccination-related lesion was defined as a clinically diagnosed herpetic lesion appearing 1 month after the index date. In the COVID-19 cohort, there was an insignificant difference in herpetic lesion incidence between the groups. However, logistic regression demonstrated that the interaction of COVID-19 with the Herpesviridae carrier status was statistically significant. For the vaccination cohort, the data showed statistically significant differences between groups in herpetic frequencies, which manifested as an almost 2-fold odds of developing a herpetic lesion. In conclusion, following the analysis of two large cohorts, there is evidence to support the contribution of both COVID-19 and the mRNA vaccine to the reactivation of Herpesviridae. Our results diminish the idea that COVID-19 has unique, herpetic-like lesions.

The association of circulating endocannabinoids with neuroimaging and blood biomarkers of neuro-injury.

BACKGROUND: Preclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs and eCB-like molecules with early markers of neurodegeneration and neuro-injury and tested for effect modification by sex. METHODS: This exploratory cross-sectional study included a random sample of 237 dementia-free older participants from the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011-2014), were 65 years or older, and cognitively healthy. Forty-four eCB compounds were quantified in serum, via liquid chromatography high-resolution mass spectrometry. Linear regression models were used to examine the associations of eCB levels with brain MRI measures (i.e., total cerebral brain volume, gray matter volume, hippocampal volume, and white matter hyperintensities volume) and blood biomarkers of Alzheimer's disease and neuro-injury (i.e., total tau, neurofilament light, glial fibrillary acidic protein and Ubiquitin C-terminal hydrolase L1). All models were adjusted for potential confounders and effect modification by sex was examined. RESULTS: Participants mean age was 73.3 ± 6.2 years, and 40% were men. After adjustment for potential confounders and correction for multiple comparisons, no statistically significant associations were observed between eCB levels and the study outcomes. However, we identified multiple sex-specific associations between eCB levels and the various study outcomes. For example, high linoleoyl ethanolamide (LEA) levels were related to decreased hippocampal volume among men and to increased hippocampal volume among women (ß ± SE = - 0.12 ± 0.06, p = 0.034 and ß ± SE = 0.08 ± 0.04, p = 0.026, respectively). CONCLUSIONS: Circulating eCBs may play a role in neuro-injury and may explain sex differences in susceptibility to accelerated brain aging. Particularly, our results highlight the possible involvement of eCBs from the N-acyl amino acids and fatty acid ethanolamide classes and suggest specific novel fatty acid compounds that may be implicated in brain aging. Furthermore, investigation of the eCBs contribution to neurodegenerative disease such as Alzheimer's disease in humans is warranted, especially with prospective study designs and among diverse populations, including premenopausal women.

Hospitalizations in older-adults newly diagnosed with dementia: A population-based longitudinal study in Israel.

OBJECTIVES: To compare inpatient burden (i.e. likelihood of hospitalization, number of admissions and length of stay) in persons with newly diagnosed dementia to the general population without dementia. Additionally, to evaluate whether inpatient burden is increased during the years prior to and post dementia diagnosis, and to identify factors associated with increased inpatient burden. METHOD: The Israeli National Dementia Dataset (2016) was cross-linked with the National Hospital Discharge Database of the Israeli Ministry of Health (2014-2018). Dementia definition was based on documented dementia diagnoses and/or the purchase of medications during 2016. Mixed-effects models were applied to identify demographic and health characteristics associated with inpatient burden in the one and 2 years prior to and after dementia diagnosis. RESULTS: The dataset included 11,625 individuals aged ≥65 years, identified as incident dementia cases. Compared to the general population of older-adults without dementia, those with newly diagnosed dementia had a higher age-standardized proportion of hospitalizations (26.4% vs. 40%). The odds for hospitalization were highest during the year preceding dementia diagnosis (OR = 3.19, 95% CI 2.51-4.06) compared to 2 years prior to diagnosis, and remained high (although slightly decreased) after dementia diagnosis. Older age was associated with inpatient burden after, but not prior to dementia diagnosis. CONCLUSIONS: Older persons with dementia are a vulnerable population group with increased utilization of inpatient burden compared to those without dementia, particularly in the years surrounding dementia diagnosis. Sociodemographic risk factors may differ with respect to the time surrounding dementia diagnosis.

Consumption of Ultra-Processed Food and Cognitive Decline among Older Adults With Type-2 Diabetes.

BACKGROUND: Ultra-processed food (UPF) consumption is related to increased morbidity and mortality. However, knowledge on its association with cognitive function is lacking. In this longitudinal study, we examined the associations between UPF intake and cognitive decline in older adults with type-2 diabetes (T2D). METHODS: The sample included initially nondemented T2D older adults (≥65 years), from the Israel Diabetes and Cognitive Decline study, who had complete information on nutrition at baseline and at least 3 cognitive assessments (mean follow-up 5.3 ± 1.5 years). Nutritional intake was evaluated by a validated Food-Frequency Questionnaire, and foods were categorized as UPF based on NOVA classification. Percent of calories from UPF were calculated from total caloric consumption in total and specific food groups. Mixed effect models were used to examine the link between UPF intake (top vs bottom quartiles) and change in cognitive function overall and in specific domains, adjusting for potential confounders. RESULTS: Of the total sample (N = 568; mean age 71.3 ± 4.5 years, 60% men), 141 consumed >31% kcal from UPF (top quartile). Greater intake of ultra-processed meat was associated with a faster decline in executive functions and global cognition (ß = -0.041 ± 0.013; p = .002 and ß = -0.026 ± 0.010; p = .011, respectively). Additionally, consumption of ultra-processed oils/spreads was associated with faster decline in executive functions and global cognition (ß = -0.037 ± 0.014; p = .006 and ß = -0.028 ± 0.010; p = .009, respectively). Total UPF consumption and UPF-derived from dairy products and bread/pastries/starch were not associated with cognitive change. CONCLUSION: This study suggests that a high intake of ultra-processed meat and oils/spreads may be associated with accelerated cognitive decline in older individuals with T2D.

Ophthalmic Assessment in Patients With Darier Disease.

PURPOSE: To assess the prevalence of ophthalmic findings in patients with Darier disease, an autosomal dominant genetic skin disorder, in an effort to evaluate the need for eye examinations in the management of the disease. DESIGN: Prospective observational case series. METHODS: Thirty-six individuals with Darier disease were evaluated by both ocular assessment questionnaire and a comprehensive ophthalmic examination (visual acuity, refraction, external examination, and slit-lamp examination) with emphasis on the eyelids, conjunctiva, and cornea. In addition, questionnaire-based medical interview and skin examination were conducted. RESULTS: According to the medical questionnaire, 39% of patients reported eye problems, 36% dry eye, and 42% eye fatigue after prolonged reading. Ocular examination revealed Darier disease lesions on the eyelids in 55% of the patients, blepharitis in 44%, conjunctival hyperemia in 28%, and short tear film break-up time in 83%. There was no significant relationship between any of these ophthalmic findings and systemic retinoid therapy, sex, or age. CONCLUSIONS: The high prevalence of blepharitis and dry eye highlights the importance of ophthalmologic evaluation of patients with Darier disease.

An Update on the Cutaneous Manifestations of Darier Disease.

BACKGROUND: Knowledge about the clinical features of Darier disease, an orphan autosomal-dominant genetic disorder, is sparse and has been evaluated only in few studies. OBJECTIVES: To investigate the clinical features of a large group of patients with Darier disease, and to explore for associations between disease characteristics and severity of the disease. METHODS: Seventy-six individuals with Darier disease were evaluated utilizing a structured questionnaire-based interview, a physical examination, and a retrospective assessment of their medical records. RESULTS: The most frequent locations of lesions were hands (99%) and fingernails (93%). Wart-like lesions on the hands were more visible after soaking them in water for 5 minutes, we therefore named this phenomenon the "wet hand sign". Oral involvement was found in 43% of patients, while 48% of women and 16% of men showed genital lesions. Patients with severe Darier disease had a tenfold greater risk of developing genital lesions than those with mild disease (P = .01). Most patients (88%) in our study exhibited a combination of the four types of the disease patterns of distribution (flexural, seborrheic, nevoid, and acral). CONCLUSIONS: Documentation of disease on the hands and fingernails provides a highly sensitive means to aid in the diagnosis of Darier disease. It is important to evaluate mucosal lesions including genital and oral mucosa.

A study of ethnic, gender and educational differences in attitudes toward COVID-19 vaccines in Israel - implications for vaccination implementation policies.

BACKGROUND: Vaccines for COVID-19 are currently available for the public in Israel. The compliance with vaccination has differed between sectors in Israel and the uptake has been substantially lower in the Arab compared with the Jewish population. AIM: To assess ethnic and socio-demographic factors in Israel associated with attitudes towards COVID-19 vaccines prior to their introduction. METHODS: A national cross-sectional survey was carried out In Israel during October 2020 using an internet panel of around 100,000 people, supplemented by snowball sampling. A sample of 957 adults aged 30 and over were recruited of whom 606 were Jews (49% males) and 351 were Arabs (38% males). RESULTS: The sample of Arabs was younger than for the Jewish respondents. Among the men, 27.3% of the Jewish and 23.1% of the Arab respondents wanted to be vaccinated immediately, compared with only 13.6% of Jewish women and 12.0% of Arab women. An affirmative answer to the question as to whether they would refuse the vaccine at any stage was given by 7.7% of Jewish men and 29.9% of Arab men, and 17.2% of Jewish women and 41.0% of Arab women. Higher education was associated with less vaccine hesitancy. In multiple logistic regression analysis, the ethnic and gender differences persisted after controlling for age and education. Other factors associated with vaccine hesitancy were the belief that the government restrictions were too lenient and the frequency of socializing prior to the pandemic. CONCLUSIONS: The study revealed a relatively high percentage reported would be reluctant to get vaccinated, prior to the introduction of the vaccine. This was more marked so for Arabs then Jews, and more so for women within the ethnic groups. While this was not a true random sample, the findings are consistent with the large ethnic differences in compliance with the vaccine, currently encountered and reinforce the policy implications for developing effective communication to increase vaccine adherence. Government policies directed at controlling the pandemic should include sector-specific information campaigns, which are tailored to ensure community engagement, using targeted messages to the suspected vaccine hesitant groups. Government ministries, health service providers and local authorities should join hands with civil society organizations to promote vaccine promotion campaigns.

High ambient temperature in summer and risk of stroke or transient ischemic attack: A national study in Israel.

OBJECTIVE: To examine whether high ambient temperature and diurnal temperature range during the summer are associated with risk of stroke/transient ischemic attack (TIA). METHODS: A time-stratified case-crossover study design was conducted. The study sample comprised all individuals aged ≥50 years who had a stroke/TIA reported to the Israeli National Stroke Registry between 2014 and 2016 during the summer season. Daily temperature data were retrieved from the Israel Meteorological Service. Conditional logistic regression models were used with relative humidity and air pollution as covariates. RESULTS: The sample included 15,123 individuals who had a stroke/TIA during the summer season (mean age 73 ± 12 years; 54% males). High ambient temperature was associated with stroke/TIA risk starting from the day before the stroke event, and increasing in strength over a six-day lag (OR = 1.10 95%CI 1.09-1.12). Moreover, a larger diurnal temperature range prior to stroke/TIA occurrence was associated with decreased stroke/TIA risk (OR = 0.96 95%CI 0.95-0.97 for a six-day lag). CONCLUSIONS: High ambient temperature may be linked to increased risk of cerebrovascular events in subsequent days. However, relief from the heat during the night may attenuate this risk.

Serum corin is reduced and predicts adverse outcome in non-ST-elevation acute coronary syndrome.

BACKGROUND AND OBJECTIVES: The aim of the current study was to describe the role of corin, an enzyme that cleaves pro-atrial natriuretic peptide and pro-brain natriuretic peptide into their active peptides, in patients with acute coronary syndrome (ACS). METHODS: Serum corin level was studied in patients with non-ST-elevation ACS who underwent percutaneous coronary intervention (n=152) and in control volunteers (n=103). RESULTS: The corin level was lower in acute coronary syndrome patients (798±288 pg/ml) than in the controls (1165±613 pg/ml, p<0.0001). Those acute coronary syndrome patients who developed major adverse cardiovascular events (MACE; 60.9%) within 3 years of discharge had lower corin levels than the patients who did not experience major adverse cardiovascular events (698.16±233.67 vs. 952.1±297.81 pg/ml, p<0.0001). Using a multiple logistic regression model, corin level was a significant predictor of post-ACS MACE: p=0.0004 for 50 pg/ml steps, AUC 0.791, while p<0.0001, and AUC 0.804 using corin and brain natriuretic peptide as predictors. CONCLUSIONS: Patients with non-ST-elevation ACS have lower serum corin levels than controls. Corin levels are lower in ACS patients who later experience MACE and thus might be predictor for MACE. This new putative biomarker may be useful, either alone or in combination with other biomarkers, for cardiovascular risk stratification assessment and outcome prediction in ACS patients.

Correlation between stillbirth vital statistics and medical records.

OBJECTIVE: Most data regarding conditions associated with or contributing to stillbirth are derived from fetal death certificates. Our purposes were to compare stillbirth data recorded in vital statistics with those in the medical record and to investigate whether diagnostic evaluations differed in tertiary care and community hospitals. METHODS: In this cross-sectional study, fetal death certificate data identified individuals with stillbirths delivering in eight Salt Lake City hospitals from 1998 to 2002. Medical records were reviewed to assess demographics, diagnostic evaluation, and potential causes of stillbirth. Data were compared between death certificates and the medical record by calculation of the κ coefficient for categorical variables or Kendall's τ-b coefficients based on the number of concordant and discordant pairs of observations for continuous variables. Diagnostic tests completed were compared between community and tertiary care hospitals with χ or Fisher exact test. RESULTS: Five-hundred fifty-six individuals were identified, and 461 (83%) charts were available for review. Correlation between death certificates and the medical record was nearly perfect for demographic variables (correlation 0.8-0.9) but slight to moderate (correlation 0.2-0.5) for contributing or etiologic factors. Important diagnostic tests performed significantly more often in tertiary care than community hospitals included autopsy (35% compared with 13%, P<.01), karyotype (17% compared with 4%, P<.01), Kleihauer-Betke (22% compared with 13%, P=.01), toxicology screen (13% compared with 2%, P<.01), and complete blood count (95% compared with 90%, P=.03). CONCLUSION: There are important discrepancies between fetal death certificates and medical records. Complete work-up, review of the medical record, and efforts to increase accurate reporting may improve the accuracy of stillbirth vital statistics. Diagnostic evaluation was more extensive in tertiary care hospitals.

Reduced glomerular filtration rate in asymptomatic diabetic patients: predictor of increased risk for cardiac events independent of albuminuria.

OBJECTIVES: This study aimed to investigate the prevalence of a reduced glomerular filtration rate (GFR) with and without albuminuria and its ability to predict cardiac events in asymptomatic diabetic patients undergoing stress-rest thallium-201 myocardial perfusion single-photon emission computed tomography. BACKGROUND: Diabetic patients have a higher prevalence of asymptomatic coronary heart disease. Therefore, identifying predictors of cardiac events in asymptomatic diabetic patients is needed. METHODS: In 269 asymptomatic patients, baseline evaluation included diabetes-related complications, including creatinine clearance (CrCl) and albuminuria. During follow-up (mean 2.3 +/- 1.0 years), all cardiac events were recorded. RESULTS: Seventy-seven patients (29%) had a reduced GFR defined by CrCl <60 ml/min/1.73 m(2). Compared with the 177 patients with CrCl >/=60 ml/min/1.73 m(2), the reduced GFR group was older (p < 0.0001), had a longer duration of diabetes (p = 0.002), and had a higher prevalence of albuminuria (p = 0.04). Nevertheless, 35% of the reduced GFR group had normoalbuminuria. Patients with reduced GFR had a significant two-fold increase in total cardiac events (unstable angina, nonfatal myocardial infarction, and cardiac procedures) (25% vs. 13%, p = 0.019), and multivariate analysis found that reduced GFR was an independent predictor of cardiac events (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1 to 4.46). Other independent predictors of cardiac events included stress-induced abnormal myocardial perfusion imaging (OR 3.1, 95% CI 1.3 to 7.5), an electrocardiographic ischemic response (OR 2.7, 95% CI 1.01 to 7.14), and peripheral artery disease (OR 2.1, 95% CI 1.05 to 4.23); however, albuminuria was not. CONCLUSIONS: A reduced GFR was common in our group of asymptomatic diabetic patients and was associated with a two-fold increase in cardiac events. Multivariate analysis found that reduced GFR independent of albuminuria was a significant predictor of cardiac events.