Age related weight loss in female 5xFAD mice from 3 to 12 months of age.

In addition to cognitive decline, patients with Alzheimer's disease (AD) exhibit sensory, motor, and neuropsychiatric deficits. Many AD patients also show weight loss, suggesting that AD may involve a metabolic syndrome. The 5xFAD mouse model shows age-related weight loss compared to wildtype controls, and thus may exhibit metabolic dysfunction. This longitudinal study measured age-related weight loss in female 5xFAD and B6SJL/JF2 wild-type mice from 3 to 12 months of age, and examines some of the behavioural and physiological phenotypes in these mice that have been proposed to contribute to this weight loss. Because some mice had to be singly housed during the study, we also examined genotype by housing interactions. The 5xFAD mice weighed less and ate less than WT littermates starting at 6 months of age, exhibited less home cage activity, had higher frailty scores, less white adipose tissue, and lower leptin expression. At 9 and 12 months of age, heavier 5xFAD mice performed better on the rotarod, suggesting that metabolic deficits which begin between 6 and 9 months of age may exacerbate the behavioural deficits in 5xFAD mice. These results indicate that the 5xFAD mouse is a useful model to study the behavioural and metabolic changes in AD.

Sugar intake and craving during alcohol withdrawal in alcohol use disorder inpatients.

To assess whether changes in sugar intake and craving occur during alcohol withdrawal in humans, we conducted a prospective, observational study in a university hospital addictions treatment center. Recruited patients had severe alcohol use disorder and were hospitalized for 7 days in the short-stay unit for alcohol withdrawal and then for 6 weeks in the rehabilitation unit. During the hospital stay, they had no access to alcohol but had full access to sweet products and beverages in a shop and vending machines located inside the hospital. Alcohol craving was assessed using a visual analogue scale on Days 1, 15, and 45. Sugar craving, sweet products stored by patients in their rooms, and weight were assessed on the same days. Thirty-five patients were included. Sugar craving increased in 14 patients during the hospital stay, whereas no change was observed in the remaining 21. Significant increases in both the amounts of sweet products stored in the patients' rooms (p < 0.02) and weight (p < 0.05) were observed only in the sugar craving group. During the same period, alcohol craving decreased significantly in all patients. Changes in tobacco smoking were not different according to the sugar craving status and therefore cannot explain the observed differences. In conclusion, increased intake and craving for sugar after alcohol withdrawal were observed in 40% of the patients included in our prospective study, and these results were similar to those of a study conducted in the alcohol post-dependent state model in rats.

Adiposity-related insulin resistance and thickness of the cerebral cortex in middle-aged adults.

The thickness of the cerebral cortex decreases with ageing. Recent research suggests that obesity and type 2 diabetes mellitus may accelerate this cortical thinning, and that obesity-related insulin resistance may be a shared mechanistic pathway. Ageing of the cerebral cortex demonstrates sex-specific trajectories, with a gradual shift towards accelerated thinning beginning in midlife. Here, we investigated whether adiposity-related insulin resistance is associated with lower thickness of the human cerebral cortex in a community-based sample of middle-aged adults. We studied 533 adult participants (36-65 years) from the Saguenay Youth Study. Adiposity was assessed with bioimpedance, and insulin resistance was evaluated from a fasting blood sample with the homeostatic model assessment of insulin resistance (HOMA-IR). Associations between adiposity-related insulin resistance (adiposity/IR) and cortical thickness were assessed with linear models, separately in males and females younger or older than 50 years. Potential biological underpinnings were investigated with virtual histology. Adiposity/IR was associated with lower cortical thickness in females older than 50 years but not in males or younger females. The strength of the association varied across the cerebral cortex, with regions of the lateral frontal and parietal cortices and the superior temporal cortex demonstrating most pronounced thinning. Based on virtual histology, adiposity/IR-related cortical thinning may involve neurones, astrocytes, oligodendrocytes and ependymal cells acting so that they lower the cortical potential for synaptogenesis, formation of dendritic spines, production of extracellular matrix and myelination. Adiposity-related insulin resistance is associated with lower cortical thickness in middle-aged women older than 50 years. This aspect of thinning may involve neuronal and glial cells in a way that lowers the capacity of the cerebral cortex for neuronal plasticity and maintenance of myelination.

Role of Patient Sex in Early Recovery from Alcohol-Related Cognitive Impairment: Women Penalized.

BACKGROUND: The objective was to explore the role of patient sex in cognitive recovery and to identify predictive factors for non-recovery in alcohol use disorder (AUD). METHODS: All patients with AUD admitted to a residential addictions treatment center were systematically assessed at admission and after 6 weeks of abstinence in a controlled environment. The inclusion criteria were that patients were admitted for AUD with baseline alcohol-related cognitive impairment (baseline total Montreal Cognitive Assessment (MoCA) score < 26) and reassessed at 6 weeks (n = 395). A logistic regression model was built to determine the influence of sex on recovery status (MoCA < or ≥ 26) taking into account the interaction effect of sex with alcohol consumption on cognitive function. RESULTS: The mean age was 50.10 years (SD = 9.79), and 27.41% were women. At baseline, the mean MoCA scores were 21.36 (SD = 3.04). Participants who did not achieve recovery (59.3% of women vs 53.8% of men) had lower total MoCA scores at baseline. The 2 factors that was significantly and independently associated with non-recovery and with a non-zero coefficient was being a woman and initial MoCA score (respective adjusted odds ratios (AOR) = 1.5 and 0.96, p-values < 0.05). CONCLUSIONS: These results could influence the time required in a controlled environment to maintain abstinence and the duration of in-care for women.

Visceral fat-related systemic inflammation and the adolescent brain: a mediating role of circulating glycerophosphocholines.

OBJECTIVE: Life-long maintenance of brain health is important for the prevention of cognitive impairment in older age. Low-grade peripheral inflammation associated with excess visceral fat (VF) may influence brain structure and function. Here we examined (i) if this type of inflammation is associated with altered white-matter (WM) microstructure and lower cognitive functioning in adolescents, and (ii) if recently identified circulating glycerophosphocholines (GPCs) can index this type of inflammation and associated variations in WM microstructure and cognitive functioning. SUBJECTS: We studied a community-based sample of 872 adolescents (12-18 years, 48% males) in whom we assessed VF and WM microstructure with magnetic resonance imaging, processing speed with cognitive testing, serum C-reactive protein (CRP, a common marker of peripheral inflammation) with a high-sensitivity assay, and serum levels of a panel of 64 GPCs with advanced mass spectrometry. RESULTS: VF was associated with CRP, and CRP in turn was associated with "altered" WM microstructure and lower processing speed (all p < 0.003). Further, "altered" WM microstructure was associated with lower processing speed (p < 0.0001). Of all 64 tested GPCs, 4 were associated with both VF and CRP (at Bonferroni corrected p < 0.0004). One of them, PC16:0/2:0, was also associated with WM microstructure (p < 0.0001) and processing speed (p = 0.0003), and mediated the directed associations between VF and both WM microstructure (p < 0.0001) and processing speed (p = 0.02). As a mediator, PC16:0/2:0 explained 21% of shared variance between VF and WM microstructure, and 22% of shared variance between VF and processing speed. Similar associations were observed in an auxiliary study of 80 middle-aged adults. CONCLUSIONS: Our results show that VF-related peripheral inflammation is associated with "altered" WM microstructure and lower cognitive functioning already in adolescents, and a specific circulating GPC may be a new molecule indexing this VF-related peripheral inflammation and its influences on brain structure and function.

Proapelin is processed extracellularly in a cell line-dependent manner with clear modulation by proprotein convertases.

Apelin is a peptide hormone that binds to a class A GPCR (the apelin receptor/APJ) to regulate various bodily systems. Upon signal peptide removal, the resulting 55-residue isoform, proapelin/apelin-55, can be further processed to 36-, 17-, or 13-residue isoforms with length-dependent pharmacological properties. Processing was initially proposed to occur intracellularly. However, detection of apelin-55 in extracellular fluids indicates that extracellular processing may also occur. To test for this, apelin-55 was applied exogenously to HEK293A cells overexpressing proprotein convertase subtilisin kexin 3 (PCSK3), the only apelin processing enzyme identified thus far, and to differentiated 3T3-L1 adipocytes, which endogenously express apelin, PCSK3 and other proprotein convertases. Analysis of culture media constituents from each cell type by high performance liquid chromatography-mass spectrometry and western blot demonstrated a time-dependent decrease in apelin-55 levels. This decrease was partially, but not fully, attenuated by PCSK inhibitor treatment in both cell lines. Comparison of the resulting apelin-55-derived peptide profile between the two cell lines demonstrated distinct processing patterns, with apelin-36 production apparent in 3T3-L1 adipocytes vs. detection of the prodomain of a shorter isoform (likely the apelin-13 prodomain, observed after additional proteolytic processing) in PCSK3-transfected HEK293A cells. Extracellular processing of apelin, with distinct cell type dependence, provides an alternative mechanism to regulate isoform-mediated physiological effects of apelin.

Comparison of the MoCA and BEARNI tests for detection of cognitive impairment in in-patients with alcohol use disorders.

INTRODUCTION: Screening of cognitive impairment is a major challenge in alcoholics seeking treatment, since cognitive dysfunction may impair the overall efficacy of rehabilitation programs and consequently increase relapse rate. We compared the performance of two screening tools: the MoCA (Montreal Cognitive Assessment), which is widely used in patients with neurological diseases and already used in patients with alcohol use disorder (AUD), and the BEARNI (Brief Evaluation of Alcohol-Related Neuropsychological Impairments), a recent test specifically developed for the alcoholic population. METHODS: We compared the sensitivity and specificity of the MoCA and the BEARNI in a sample of AUD patients with and without cognitive impairment assessed by a battery of neuropsychological tests. RESULTS: Ninety patients were included. There were 67 men and 23 women aged 48.9 ±â€¯9.6 years. According to the neuropsychological tests, 51.1% of patients had no cognitive impairment, while it was mild or moderate to severe in 31.1 and 17.8%, respectively. The BEARNI sensitivity was extremely high (1.0), since all patients with cognitive impairment were identified, but its specificity was very low (0.04). The MoCA had a lower sensitivity (0.79) than the BEARNI, but its specificity was significantly better (0.65). A detailed analysis of the BEARNI scores showed a discrepancy between the qualitative and quantitative interpretation of the test which could, at least in part, explain its low specificity. CONCLUSION: Both the MoCA and the BEARNI are screening tools which identified alcoholic patients with cognitive impairment. However, in routine use, the MoCA appeared to be more appropriate given the low specificity of the BEARNI.

Determination of MoCA Cutoff Score in Patients with Alcohol Use Disorders.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) score is a convenient and promising tool for estimating alcoholic patients' global cognitive functioning, a major challenge for all specialized alcohol treatment centers. However, whether or not the score should be corrected for education level and whether the proposed cutoff is relevant in patients with alcohol use disorders (AUD) should be determined. METHODS: We compared the MoCA scores in patients hospitalized for AUD with and without cognitive impairment assessed by a battery of neuropsychological (NP) tests. Sensitivity, specificity, and cutoff of the MoCA score were analyzed using receiver operating characteristic curve analysis. RESULTS: Thirty-one patients with and 25 without cognitive impairment were included in the study. There were 40 men and 16 women, with a mean age of 49.5 years. The mean uncorrected MoCA score was 23.1 ± 3.3 in those with and 27.0 ± 1.9 in those without cognitive impairment. NP tests were significantly correlated with the MoCA score. Uncorrected MoCA scores identified more than 80% of the patients with a cutoff score equal to 26, to obtain similar accuracy with the corrected score required using a cutoff score equal to 27. CONCLUSIONS: Our results confirm that the MoCA test is a convenient and reliable screening tool to measure cognition defects in alcoholic patients. As using the 1-point education adjustment increases the cutoff score by 1 point, it is suggested to use the noncorrected score and the usual cutoff, that is, 26. Being easy to administer and only moderately time-consuming, the MoCA score should be used extensively in addiction treatment centers.

Beneficial Effect of Alcohol Withdrawal on Gut Permeability and Microbial Translocation in Patients with Alcohol Use Disorder.

BACKGROUND: The human intestinal microbiota exerts beneficial or harmful effects in several disorders. Many factors, including alcohol consumption, may influence its composition and trigger bacterial translocation. Excessive alcohol consumption increases gut permeability and translocation of endotoxin into peripheral circulation. Although plasma endotoxin concentrations have been measured often, quantitative changes following alcohol withdrawal have never been described in subjects with alcohol use disorder (AUD). The aim of this study was to measure microbial translocation (MT) and gut permeability markers in patients with AUD, to compare these markers to healthy controls (HC) and to monitor markers during the first 6 weeks of abstinence. METHODS: Sixty-five patients with AUD and hospitalized for alcohol withdrawal were included. Epidemiological, clinical, biological, and addictological data were gathered. Blood samples were collected at baseline, then 3 and 6 weeks after alcohol withdrawal. A hundred healthy volunteers were used as controls. Three markers of MT were monitored in plasma samples: sCD14 and lipopolysaccharide-binding protein (LBP) were quantified using ELISA, and 16S rDNA was quantified using real-time polymerase chain reaction. Zonulin and intestinal fatty acid binding protein (I-FABP) blood levels were also monitored as indirect markers of gut permeability, using ELISA. RESULTS: At baseline, LBP, 16S rDNA, sCD14 and I-FABP markers were significantly higher in patients with AUD than in HC. Six weeks after alcohol withdrawal plasma levels of sCD14 and LBP decreased significantly. Cannabis consumption and body mass index (BMI) before alcohol withdrawal influenced baseline MT levels and the decrease in MT markers after 6 weeks. Finally, markers of MT and gut permeability did not correlate with each other before and after alcohol withdrawal. CONCLUSIONS: Before alcohol withdrawal, MT markers were higher in patients with AUD than in HC. After 6 weeks of abstinence, an improvement in MT markers was observed. Our data suggest that there is a link between MT, its improvement, BMI, and cannabis consumption.

Investigation of Cognitive Improvement in Alcohol-Dependent Inpatients Using the Montreal Cognitive Assessment (MoCA) Score.

Background. Cognitive dysfunction is a common feature in alcohol use disorders. Its persistence following alcohol detoxification may impair quality of life and increase the risk of relapse. We analyzed cognitive impairment changes using the Montreal Cognitive Assessment (MoCA) score in a large sample of alcohol-dependent inpatients hospitalized for at least 4 weeks. Method. This was an observational longitudinal survey. Inclusion criteria were alcohol dependence (DSM-IV) and alcohol abstinence for at least one week. The MoCA test was administered on admission and at discharge. Results. 236 patients were included. The mean MoCA score significantly increased from 22.1 ± 3.7 on admission to 25.11 ± 3.12 at discharge. The corresponding effect-size of improvement was high, 1.1 [95% CI 1.0-1.2]. The degree of improvement was inversely correlated with the baseline MoCA score. The rate of high and normal, that is, >26, MoCA values increased from 15.8% on admission to 53.8% at discharge. MoCA score improvement was not correlated with the total length of abstinence prior to admission. Conclusion. The MoCA score seems to be a useful tool for measuring changes in cognitive performance in alcohol-dependent patients. A significant improvement in cognitive function was observed whatever the degree of impairment on admission and even after a long abstinence period.

MoCA as a Screening Tool of Neuropsychological Deficits in Alcohol-Dependent Patients.

BACKGROUND: Alcoholism is known to be associated with cognitive deficits mainly concerning visuospatial capacity, executive function, memory, and attention. These impairments may affect treatment efficacy which should therefore be adapted. We evaluated the potential utility of the Montreal Cognitive Assessment (MoCA) to evaluate cognitive impairment in a large series of alcoholic patients hospitalized for withdrawal and rehabilitation. METHODS: Consecutive recruitment during a time period of patients admitted to an addiction treatment unit of a teaching hospital. Administration of the MoCA test on admission by trained staff members. RESULTS: A total of 166 patients aged 49.9 ± 9.2 years were included. Mean duration of administration was 20 minutes. The mean MoCA score was 23.5 ± 3.5 and 68.1% had an impaired value (<26). Age was negatively and education was positively associated with the MoCA score. Significant cognitive deficits concerned visuospatial capacity, attention, fluency, abstraction, and delayed recall. Neither age nor sex was significantly related to the MoCA score, while having a high education level (>12 years) significantly increased the likelihood of having a high MoCA score. CONCLUSIONS: Owing to their severity and frequency, screening for cognitive deficits is necessary in alcoholics during rehabilitation. MoCA is an appropriate tool for this purpose.

Feasibility and Efficacy of an Addiction Treatment Program in Patients With Upper Aerodigestive Tract Cancer.

BACKGROUND: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. METHOD: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. RESULTS: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). CONCLUSION: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

Wine consumption is not associated with a decreased risk of alcoholic cirrhosis in heavy drinkers.

AIMS: While it was thought that all alcoholic beverages share a similar liver toxicity when drunk at a high level, recent epidemiological surveys have suggested that wine drinking might decrease the risk of alcoholic cirrhosis in heavy drinkers. Therefore, we performed a study aiming to analyse the type and the intake levels of alcoholic beverages in heavy drinkers according to the severity of the liver disease. METHODS: This is a case-control study enrolling 42 cirrhotic and 60 non-cirrhotic patients. Liver status was assessed using clinical, biological, histological and ultrasonographic procedures. Alcohol consumption was recorded using the Lifetime Drinking History method. RESULTS: We did not find any significant differences in total alcohol consumption between cases and controls and, moreover, in our series, the relative percentage of pure alcohol drunk in wine was significantly higher in cirrhotic, than in non-cirrhotic, patients. CONCLUSIONS: Our results confirm that the absence of a link between the type of alcoholic beverage and the occurrence of cirrhosis is still valid.