Use of different anticholinergic scales and their correlation with anticholinergic symptom burden in a cohort of people living with HIV.

OBJECTIVES: How to detect the clinical impact of anticholinergic (AC) burden in people with HIV (PWH) remains poorly investigated. We cross-sectionally described the prevalence and type of AC signs/symptoms and the screening accuracy of three AC scales in detecting their presence in a modern cohort of PWH. METHODS: We calculated AC Burden Scale (ABS), AC Risk Score (ARS) and AC Drug Score (ADS) in 721 adult PWH and recorded the presence of AC signs/symptoms over the previous 3 months. High AC risk was defined by ABS score ≥2, and ARS or ADS score ≥3. Comparisons among the scale were based on Cohen's inter-rater agreement, and their screening accuracy was assessed by receiver operating characteristics (ROC) curves and performance measures. RESULTS: We enrolled 721 PWH, of whom 72.0% of participants were male; the median age was 53 years, and 164 participants (22.7%) were on at least one AC drug. Among these, 28.6% experienced at least one AC sign/symptom. Agreement in AC risk classification was substantial only between ARS and ADS (k = 0.6). Lower and higher risk of AC signs/symptoms was associated with dual regimens [adjusted OR (aOR) = 0.12 versus three-drug regimens, P = 0.002] and increasing number of AC drugs (aOR = 12.91, P < 0.001). Depression and COPD were also associated with higher risk of AC signs/symptoms in analysis unadjusted for number of AC drugs. ABS and ADS showed the best area under the ROC curve (AUROC) of 0.85 (0.78-0.92) and 0.84 (0.75-0.92; P < 0.001 for both). However, at the cut-off used for the general population, the sensitivity of all three scales was very low (34.0%, 46.8% and 46.8%). CONCLUSIONS: Up to one-fourth of participants in our cohort were exposed to at least one AC drug, and among them AC signs/symptoms affected more than one-fourth. Both polypharmacy (as number of antiretrovirals and of co-medications with AC properties) and to a lesser extent specific comorbidities shaped the risk of developing AC signs/symptoms. Sensitive screenings for AC risk in PWH should prefer ABS or ADS based on lower cut-offs than those suggested for the general population.

The Role of Cognitive Reserve in Protecting Cerebellar Volumes of Older Adults with mild Cognitive Impairment.

The present study aims to investigate the relationship between cerebellar volumes and cognitive reserve in individuals with Mild Cognitive Impairment (MCI). A description of proxies of cerebellar cognitive reserve in terms of different volumes across lobules is also provided. 36 individuals with MCI underwent neuropsychological (MoCA, MMSE, Clock test, CRIq) assessment and neuroimaging acquisition with magnetic resonance imaging at 3 T. Simple linear correlations were applied between cerebellar volumes and cognitive measures. Multiple linear regression models were then used to estimate standardized regression coefficients and 95% confidence intervals. Simple linear correlations between cerebellar lobules volumes and cognitive features highlighted a significant association between CRIq_Working activity and specific motor cerebellar volumes: Left_V (ρ = 0.40, p = 0.02), Right_V (r = 0.42, p = 0.002), Vermis_VIIIb (ρ = 0.47, p = 0.003), Left_X (ρ = -0.46, p = 0.002) and Vermis_X (r = 0.35, p = 0.03). Furthermore, CRIq_Working activity scores correlated with certain cerebellar lobules implicated in cognition: Left_Crus_II, Vermis VIIb, Left_IX. MMSE was associated only with the Right_VIIB volume (r = 0.35, p = 0.02), while Clock Drawing Test scores correlated with both Left_Crus_I and Right_Crus_I (r = -0.42 and r = 0.42, p = 0.02, respectively). This study suggests that a higher cognitive reserve is associated with specific cerebellar lobule volumes and that Working activity may play a predominant role in this association. These findings contribute to the understanding of the relationship between cerebellar volumes and cognitive reserve, highlighting the potential modulatory role of Working activity on cerebellum response to cognitive decline.

Implication of acute tubular injury in minimal change nephrotic syndrome.

While acute tubular injury (ATI) is known to occur in a significant number of minimal change disease (MCD) nephrotic syndrome cases with acute kidney injury (AKI), the clinical significance is not certain, and AKI may also occur without ATI. This study aimed to evaluate whether the severity of AKI defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria correlated with the presence or severity of ATI in a series of adult patients with MCD. We also looked at whether time to remission of nephrotic syndrome (NS) with treatment correlated with the presence of ATI in those with and without AKI. We excluded patients with secondary MCD. Of 61 patients, 20 had AKI (33%). ATI was significantly more likely to occur in those with AKI than in those without AKI (60 vs. 24%). Overall, the severity of AKI did not clearly correspond with the severity of ATI. Remission rates at 4 weeks were lowest (25%) in those with both AKI and ATI, while they were highest (100%) in those with neither AKI nor ATI. Patients with AKI but no ATI and those with no AKI but having ATI were intermediate in remission rates and similar to each other (60 and 62%, respectively). The time to remission in the group of those without AKI was significantly longer in those with ATI than in those without (p = 0.0027), but the numerical difference in remission did not reach statistical significance in the smaller group of AKI patients. Patients with ATI were older and more often male than those without ATI. It appears that having ATI may predict a slower remission rate in MCD though the reason for this is unclear. The different demographics of those with ATI may also play a role.

Shorter observation times and smaller gauge needles in outpatient kidney biopsies.

Controversy exists as to the optimal observational time (OT) after outpatient percutaneous kidney biopsy. Further, there is some uncertainty about the benefit of smaller (18-gauge) vs. larger (16-gauge) biopsy needles. At our institution, we have been lowering the OT after outpatient kidney biopsies. Initially in 2015, we were monitoring for 6 hours and gradually began to decrease the OT over time. From 2020, we have adopted an OT of less than 4 hours. During this time period (in 2018), we also began using a smaller gauge needle (18 gauge). We reviewed all outpatient kidney biopsies performed by the nephrology division at our institution since 2015. There were 137 biopsies reviewed. 63 had OT of 4 - 6 hours, and 74 had OT < 4 hours. There was a total of 4 significant complications (2.9%). Two complications, symptomatic retroperitoneal bleeds, were detected in less than 3 hours. The other 2 complications were seen at 9 hours (clot retention) and 72 hours (retroperitoneal bleed after anticoagulation restarted). 63% of the biopsies were done using 18-gauge needles with 1 complication in this group vs. 3 in the 16-gauge group. All cases had adequate tissue for interpretation based on the ability to make a kidney diagnosis. The number of glomeruli obtained in the 18-gauge group was 29 ± 13 glomeruli, and in the 16-gauge group was 25 ± 10, which did not differ between groups. In summary, in an outpatient population, all significant post-biopsy complications were evident either within the first 3 hours or after 9 hours, and this suggests the feasibility of using shorter than standard OT in outpatient kidney biopsies. Furthermore, an 18-gauge needle may lower the risk of complications and obtain adequate tissue.

Social interaction level modulates the impact of frailty on cognitive decline: a longitudinal study.

OBJECTIVES: This study evaluates whether social interaction level modifies the association between frailty and cognitive decline in older adults. METHODS: A total of 2701 adults aged ≥65 years enrolled in the Progetto Veneto Anziani (Pro.V.A.), participated in the study. At baseline, participants were classified as having low, moderate, or high social interactions based on: cohabiting status, frequency of contacts with relatives/friends or involvement in childcare activities, and frequency of participation in social or community activities. Baseline frailty was defined as the presence of ≥3 criteria among: weight loss, weakness, slowness, low physical activity, and exhaustion. Cognitive function was assessed through the Mini-Mental State Examination (MMSE) at baseline and after 4.4 and 7 years. The association between frailty and MMSE changes over time was evaluated through linear mixed models. Interaction and subgroup analyses explored the modifying effect of social interaction level on the above association. RESULTS: The mean age of participants was 76.1 years, and 59.1% were women. Frail individuals had a steeper annual MMSE decline than their non-frail counterparts (ß=-0.40, 95%CI: -0.59, -0.20). When stratifying participants by social interaction level, we found that the association between frailty and MMSE changes over time was stronger in those with low social interactions (ß=-0.74, 95%CI: -1.33, -0.15) while attenuated in those with moderate (ß=-0.42, 95%CI: -0.74, -0.11) or high social interaction level (ß=-0.29, 95%CI: -0.58, 0.01). CONCLUSION: Maintaining frequent social interactions might mitigate the negative impact of frailty on older people's cognitive functions.

The Association between Cognitive Reserve and Depressive Mood in Older Inpatients: Gender and Age Differences.

Cognitive Reserve (CR) plays a protective role in neurological and acute/chronic diseases. Its effect on mood, however, is still unclear, although it may be relevant in a hospital setting. We aimed to explore the relationship between CR and depressive mood in older inpatients, evaluating possible gender- and age-related differences. This study involved 86 inpatients aged ≥65 years with an MMSE ≥15. Participants underwent a multidimensional evaluation that included the assessment of CR with the Cognitive Reserve Index questionnaire, divided into three sections (Education, Working Activity, and Leisure Time). Depressive mood was assessed with the 15-item Geriatric Depression Scale (GDS). The relationship between CR and GDS was evaluated by multivariable linear regressions. Significant inverse associations between CR and GDS scores emerged in the total sample (ß = -0.03 [SD = 0.02], p = .047), especially in men (ß = -0.05 [SD = 0.02], p = .005) and in individuals aged <85 years (ß = -0.07 [SD = 0.03], p = .01). Among the single CRI sections, CRI-Leisure Time was significantly associated with GDS in the total sample, in men, and participants <85 years. CR seems to be inversely associated with depressive mood in older inpatients. This relationship is particularly marked for CR related to Leisure Time, which may be modifiable even in older age through social support and interaction.

Scoping Review of Cannabis-Reduction Psychosocial Interventions and Reasons for Use among Young Adults with Psychosis.

Objective: No evidence-based intervention effectively reduces cannabis use in young adults with psychosis (YAP). To generate hypotheses about why, a scoping review was conducted to synthesize evidence about motivations for cannabis use and reduction/cessation for YAP and the psychosocial interventions trialed to identify possible gaps between motivations and interventive strategies. Methods: A systematic literature search was conducted in December, 2022. Reviews of titles and abstracts (N = 3,216) and full-texts (n = 136) resulted in 46 articles. Results: YAP use cannabis for pleasure, to reduce dysphoria, and for social and recreational reasons; motivations for cessation include insight about cannabis-psychosis interactions, incompatibility with goals and social roles, and support from social networks. Interventions with at least minimal evidence of efficacy include motivational interviewing, cognitive-behavioral strategies, and family skills training. Conclusions: Authors recommend additional research on mechanisms of change and motivational enhancement therapy, behavioral activation, and family-based skills interventions matched to YAP motivations for use/cessation.

Provider Intentions to Implement Cannabis Use Intervention in First Episode Psychosis Treatment.

Young adults with first episode psychosis use cannabis at high rates. In light of progressively tolerant attitudes toward cannabis, decreased perceptions of risk, and limited implementation of substance use modules within coordinated specialty care (CSC) programs, this study sought to describe factors contributing to CSC providers' intentions to implement motivational enhancement therapy (MET) for cannabis reduction. Two focus groups were conducted with CSC providers (n = 14), with questions guided by theory of planned behavior. Content and thematic analyses were conducted to identify salient themes associated with the theory. Participants generally indicated intentions to implement MET; limiting factors included concerns about clients' willingness to discuss cannabis use, perception of support for abstinence-only goals, and concerns about intervention mechanics such as computerized assessments. To reduce barriers limiting provider intention to implement MET, authors recommend training on assessment protocols, the merits of harm-reduction, and strategies for lower-risk cannabis use.Please confirm if the author names are presented accurately and in the correct sequence. Author 1 Given name: [Ryan] Last name [Petros]. Author 2 Given name: [Denise D.] Last name [Walker]. Author 3 Given name: [Adam] Last name [Davis]. Author 4 Given name: [Maria] Last name [Monroe-DeVita]. Also, kindly confirm the details in the metadata are correct.Confirmed!

Frailty, psychological well-being, and social isolation in older adults with cognitive impairment during the SARS-CoV-2 pandemic: data from the GeroCovid initiative.

BACKGROUND: The containment measures linked to the COVID-19 pandemic negatively affected the phyco-physical well-being of the population, especially older adults with neurocognitive disorders (NCDs). This study aims to evaluate whether the frailty of NCD patients was associated with different changes in multiple health domains, in particular in relation to loneliness and social isolation, pre- and post-lockdown. MATERIALS AND METHODS: Patients were recruited from 10 Italian Centers for Cognitive Disorders and Dementia. Data were collected in the pre-pandemic period (T0), during the pandemic lockdown (T1), and 6-9 months post-lockdown (T2). The UCLA Loneliness Scale-3, Activities of Daily Living (ADL), Instrumental ADL (IADL), Mini-Mental State Examination, and Neuropsychiatric Inventory (NPI) were administered. Caregivers' burden was also tested. Patients were categorized as non-frail, pre-frail, and frail according to the Fatigue, Resistance, Ambulation, Illness, and Loss of Weight scale. RESULTS: The sample included 165 subjects (61.9% women, mean age 79.5 ± 4.9 years). In the whole sample, the ADL, IADL, and NPI scores significantly declined between T0 and T2. There were no significative variations in functional and cognitive domains between the frail groups. During lockdown we recorded higher Depression Anxiety Stress Scales and Perceived Stress Scale scores in frail people. In multivariable logistic regression, frailty was associated with an increase in social isolation, and a loss of IADL. CONCLUSIONS: We observed a global deterioration in functional and neuro-psychiatric domains irrespective of the degree of frailty. Frailty was associated with the worsening of social isolation during lockdown. Frail patients and their caregivers seemed to experience more anxiety and stress disorders during SARS-CoV-2 pandemic.

Acetylcholinesterase inhibitors and cognitive stimulation, combined and alone, in treating individuals with mild Alzheimer's disease.

BACKGROUNDS: Acetylcholinesterase inhibitors (AChEI) and cognitive stimulation (CS) are the standard pharmacological and non-pharmacological treatments for Alzheimer's disease (AD). AIMS: The aim of this study was to investigate the effects of these treatments, alone or combined, on the neuropsychological profiles of patients with AD. METHODS: Forty participants were assigned to three groups receiving either only AChEI (n = 14), AChEI + CS (n = 15), or only CS (n = 11). Cognition was evaluated at baseline and after three months. Linear mixed-effects models were used to investigate differences among the treatments in terms of changes in the patients' neuropsychological profiles. RESULTS: Results, although preliminary because of the small sample size, suggest that a general improvement was found in patients who received AChEI + CS and those who received only CS compared with those who received only AChEI. Interestingly, individuals who received only CS showed a significant improvement in immediate memory recall than those who received only AChEI. Furthermore, the group receiving AChEI + CS showed an improvement in delayed recall than the other two groups. DISCUSSION: The combination of AChEI and CS seems to have the greatest benefit for patients with mild AD. More interestingly, CS alone is more effective than AChEI alone, even in improving memory, considered to be the "lost" cognitive domain in AD.

Religious assessment in Italian older adults: psychometric properties of the Francis Scale of Attitude toward Christianity and the Behavioral Religiosity Scale.

OBJECTIVES: Studies have shown that religiosity (R) and spirituality (S) can positively impact older adults' life. Nevertheless, no validated tools for measuring these constructs in the older Italian population are currently available. This study investigates the psychometric properties of two of the most common measures of R and S in the literature: the Francis Scale of Attitude toward Christianity short form (FSACsf) and the Behavioral Religiosity Scale (BRS). METHOD: 313 older Italians completed the questionnaires anonymously. The functioning of the items and the response scales, the factor structure, age invariance and internal consistency of both scales were investigated. RESULTS: Each scale defines a substantively unidimensional variable. Moreover, items seem, on the whole, to be well formulated. The values of the Rasch-Andrich thresholds suggest that the response scale of the FSACsf was adequate for measuring spirituality. However, this was not the case for BRS, where the response categories needed to be collapsed to measure behavioral religiosity properly. Age invariance was confirmed for each scale. Cronbach's α, composite reliability and person separation reliability revealed both scales to be internally consistent. DISCUSSION: The results suggest that the scales have solid psychometric properties, and can therefore be considered valid, reliable tools for investigating religiosity and spirituality in older people.

Community Mental Health Care Delivery During the COVID-19 Pandemic: Practical Strategies for Improving Care for People with Serious Mental Illness.

The COVID-19 pandemic has presented a formidable challenge to care continuity for community mental health clients with serious mental illness and for providers who have had to quickly pivot the modes of delivering critical services. Despite these challenges, many of the changes implemented during the pandemic can and should be maintained. These include offering a spectrum of options for remote and in-person care, greater integration of behavioral and physical healthcare, prevention of viral exposure, increased collaborative decision-making related to long-acting injectable and clozapine use, modifying safety plans and psychiatric advance directives to include new technologies and broader support systems, leveraging natural supports, and integration of digital health interventions. This paper represents the authors' collaborative attempt to both reflect the changes to clinical practice we have observed in CMHCs across the US during this pandemic and to suggest how these changes can align with best practices identified in the empirical literature.

Fibrinogen Levels and the Risk of Cerebrovascular Events in Older Adults With Both Depressive Symptoms and Cognitive Impairment: A Prospective Study.

Depression and cognitive impairment have been identified as risk factors for cerebrovascular events (CVE), and one of their potential etiological pathways is inflammatory status. This prospective study aims to investigate the association between inflammatory markers and the risk of CVE in a population of 2659 older adults, enrolled in the Progetto Veneto Anziani (Pro.V.A.), with depressive symptoms, cognitive impairment, or both conditions. For each individual, we assessed at baseline the presence of depressive symptoms (defined as a Geriatric Depression Scale ≥11), cognitive impairment (defined as a Mini-Mental State Examination <24), and serum levels of fibrinogen, white blood cells (WBC), and erythrocyte sedimentation rate (ESR). During a 4.4-year follow-up, 188 (7.1%) participants had CVE. Among the inflammatory markers, high fibrinogen values were associated with a 50% higher risk of CVE in the whole sample, and with a 4-fold higher risk in individuals with both depressive symptoms and cognitive impairment (hazard ratio = 4.04, 95% confidence interval: 1.45-11.23). Elevated WBC were associated with a 5% higher risk of CVE in the whole sample and in those with both conditions. No significant association was observed with the ESR. In conclusion, our study found that high fibrinogen levels may predict the risk of CVE in older people with concomitant depressive symptoms and cognitive impairment. Therefore, fibrinogen could be considered as an easily accessible aging biomarker, which might estimate the chronic inflammatory status and its potential detrimental effects on the most vulnerable older adults.

Aquapheresis: An Institutional Experience.

BACKGROUND: Aquapheresis (AQ) consists of the extracorporeal extraction of plasma water from the vascular space across a semipermeable membrane in response to a transmembrane pressure gradient. The primary utilization of AQ has been in the management of patients with diuretic resistant heart failure with a treatment goal directed to quickly eliminate the excess fluid and optimize volume status. This modality is similar to isolated ultrafiltration performed on those patients requiring dialysis, but utilizes a machine that is smaller and easier to initiate and operate compared with traditional dialysis equipment. METHOD: A retrospective study that describes the indications in which AQ was utilized at Lenox Hill Hospital. The patient list was generated by searching for the keyword "Aquaph" in our electronic health record (EHR) orders. Patients were categorized based on hospital location and indication of AQ therapy. Additional information includes duration of treatment (days), changes in creatinine (start of AQ to stop of AQ), and total volume removed. RESULTS: The search generated 28 patients; five were excluded as AQ was not initiated. In the remaining 23 patients, the mean aquapheretic volume per day was 1954 mls, with no significant change in creatinine. Indications for AQ broke out into five main categories: cardiogenic shock including post cardiothoracic procedure (10 pts); anasarca (5 pts); ATN with volume overload (4 pts); ESKD with bridge ultrafiltration between hemodialysis treatments (2 pts); and post-op volume overload (2 pts). CONCLUSION: We found that aquapheresis can be utilized in situations other than diuretic resistant heart failure. Also to consider, is the ease in which this less complicated aquapheresis equipment can be operated compared to the more complex hemodialysis equipment.

Are cytochrome P4502D6 and apolipoprotein E genotypes associated with long-term cognitive and functional changes in patients treated with donepezil?

AIM: We investigated the associations of the single-nucleotide polymorphism rs1080985 of cytochrome P4502D6 (CYP2D6) and the apolipoprotein E (APOE) genotypes with cognitive and functional changes in patients treated with donepezil. METHODS: Sixty-five outpatients with Alzheimer's disease or mixed dementia being treated with donepezil were assessed at baseline and over 27 months. Changes in cognitive status, assessed with the Mini-Mental State Examination, and in functional status, assessed by the Activities of Daily Living Scale and the Instrumental Activities of Daily Living Scale, were evaluated as a function of CYP2D6 and APOE genotypes by using linear mixed models. Multiplicative interactions between the CYP2D6 and APOE genotypes and time were investigated. RESULTS: Individuals with the mutated CYP2D6 exhibited a slower decline in total Mini-Mental State Examination scores, orientation, registration, and functional status than those with the wild type. A significant interaction between CYP2D6, APOE, and time was found for changes in the Activities of Daily Living Scale; among the ε4 carriers, those with the mutated CYP2D6 exhibited a slower decline on the Activities of Daily Living Scale than those with the wild type. CONCLUSION: The CYP2D6 and APOE genotypes may modulate the effectiveness of donepezil on cognitive and functional status.

Alzheimer Café: an approach focused on Alzheimer's patients but with remarkable values on the quality of life of their caregivers.

BACKGROUND: Alzheimer's disease (AD) affects the global quality of life of persons who suffer from it and their caregivers, because of the behavioral and psychological consequences associated with the pathology and its caring. The Alzheimer Café (AC) is one example of approach aimed to help persons and caregivers deal with their disease. AIM: This is a pilot study focusing on the efficacy of AC in relieving caregivers' and persons' burdens due to dementia. METHODS: The quality of life of both caregivers and persons who attended the AC was compared with the quality of life of those who did not. Basic and instrumental daily activities and neuropsychiatric functioning were assessed. Caregivers also answered to general well-being and caregiving burden questionnaires. The evaluation took place at the beginning of the intervention and after 1, 3, 6, 9 and 12 months. RESULTS: Caregivers who joined the AC with their persons with dementia showed to have significantly benefited in the daily care of persons with dementia, in terms of total well-being, vitality, and emotional burden. DISCUSSION: Although improvements were not observed in persons with dementia who attended the AC, significant benefits were reported by their caregivers, suggesting that the intervention may produce better management of social and economic problems and lead to better emotional support. CONCLUSIONS: The AC seems to help families of AD persons to better manage the disease, and also delay the institutionalization of these persons, which is certainly an ambitious goal for an incurable disorder such as Alzheimer's disease.

Social capital and burnout among mental healthcare providers.

BACKGROUND: Provider burnout is a critical problem in mental health services. Contributing factors have been explicated across three domains: personal, job and organizational characteristics. Of these, organizational characteristics, including workplace environment, appear to be particularly important given that most interventions addressing burnout via the other domains (e.g. bolstering personal coping skills) have been modestly effective at best. AIMS: This study builds on previous research by using social capital as a framework for the experience of work social milieu, and aims to provide a richer understanding of how workplace social environment might impact burnout and help create more effective ways to reduce burnout. METHODS: Providers (n = 40) taking part in a larger burnout intervention study were randomly selected to take part in interviews regarding their workplace environment and burnout. Participant responses were analyzed thematically. RESULTS: Workplace social milieu revolved around two primary themes: workplace social capital in provider burnout and the protective qualities of social capital in cohesive work teams that appear to mitigate burnout. CONCLUSIONS: These results imply that work environments where managers support collaboration and social interaction among work teams may reduce burnout.

Cognitive and motor reaction times in obstructive sleep apnea syndrome: A study based on computerized measures.

Obstructive Sleep Apnea Syndrome (OSAS) is mainly associated with executive dysfunction. Although delayed reaction times (RTs) in patients with OSAS have been reported, sensitivity of processing speed has not been adequately assessed. This study suggests sensitive and reliable measures to clarify whether different components of information processing speed, i.e. cognitive and motor responses, are equally impaired in OSAS. Thirty-three patients with OSAS were compared with thirty healthy controls. The MoCA test was administered to assess participants' global neuropsychological profile. Cognitive and motor reaction times were measured using a detector panel which allows to distinguish between stimulus encoding, decision processing, and selection of the appropriate motor response. Logistic regression models highlighted both MoCA test and motor RTs as the best predictors differentiating patients from healthy participants. Results support the hypothesis of a slight decline in the cognitive profile of patients with OSAS and identify significant slowing down in the motor component of responses. It could be hypothesized that slower motor responsiveness is the cause of the global cognitive profile of these patients. With aging, motor movements and RTs usually become impaired and hypoxia might accelerate the aging process by compromising first of all the motor component of RTs.