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Several important questions regarding cognitive aging and dementia in older people with multiple sclerosis (PwMS) are the focus of this narrative review: Do older PwMS have worse cognitive decline compared to older people without MS? Can older PwMS develop dementia or other neurodegenerative diseases such as Alzheimer’s disease (AD) that may be accelerated due to MS? Are there any potential biomarkers that can help to determine the etiology of cognitive decline in older PwMS? What are the neural and cellular bases of cognitive aging and neurodegeneration in MS? Current evidence suggests that cognitive impairment in MS is distinguishable from that due to other neurodegenerative diseases, although older PwMS may present with accelerated cognitive decline. While dementia is prevalent in PwMS, there is currently no consensus on defining it. Cerebrospinal fluid and imaging biomarkers have the potential to identify disease processes linked to MS and other comorbidities—such as AD and vascular disease—in older PwMS, although more research is required. In conclusion, one should be aware that multiple underlying pathologies can coexist in older PwMS and cause cognitive decline. Future basic and clinical research will need to consider these complex factors to better understand the underlying pathophysiology, and to improve diagnostic accuracy.

Purpose To develop the novel multidimensional health perceptions questionnaire (MHPQ), a self-reported assessment of health perceptions inclusive of (1) individuals beliefs about the causes and consequences of health conditions, benefits and barriers to maintaining and improving health, ability to accomplish health-related goals and control health circumstances, and the role of God and/or spirituality in health and healthcare, (2) anticipated discrimination in the healthcare systems, and (3) trust in healthcare providers and medicine, illustrated in our newly proposed Multidimensional Health Perceptions Conceptual Model. Methods We developed an initial MHPQ β item set, corresponding to domains of our conceptual model, using a patient-centered outcomes development approach. This include literature review, expert and end-user feedback, translation and language validation (specifically to Latin American Spanish), and cognitive interviewing. Results The initial 104 items of MHPQ β had excellent content validity, with a Content Validity Index of 98.1%. After expert (n = 13) feedback, translation and language validation, and cognitive interviewing among community-dwelling English-speakers (n = 5) and Spanish-speakers (n = 4), the final MHPQ β comprised 93 items rated on a five-point agreement scale (1 = Strongly disagree to 5 = Strongly agree), with a reading grade level of 6th grade in English and 8th grade in Spanish. Conclusion The MHPQ β is a promising tool to assess individuals’ health perceptions. It has excellent content validity and good reading accessibility. Future work will establish the factor structure and final item set of the MHPQ.

Background Alzheimer’s disease (AD) is a prominent cause of dementia, resulting in neurodegeneration and memory impairment. This condition imposes a considerable public health burden on both patients and their families due to the patients’ functional impairments as well as the psychological and financial constraints. It has been well demonstrated that its aetiology involves proteinopathy, mitochondriopathies, and enhanced reactive oxygen species (ROS) generation, which are some of the key features of AD brains that further result in oxidative stress, excitotoxicity, autophagy, and mitochondrial dysfunction. Objective The current investigation was created with the aim of elucidating the neurological defence mechanism of trans,trans-Farnesol (TF) against intracerebroventricular-streptozotocin (ICV-STZ)-induced Alzheimer-like symptoms and related pathologies in rodents. Materials and methods The current investigation involved male SD rats receiving TF (25–100 mg/kg, per oral) consecutively for 21 days in ICV-STZ-treated animals. An in silico study was carried out to explore the possible interaction between TF and NADH dehydrogenase and succinate dehydrogenase. Further, various behavioural (Morris water maze and novel object recognition test), biochemical (oxidants and anti-oxidant markers), activities of mitochondrial enzyme complexes and acetylcholinesterase (AChE), pro-inflammatory (tumor necrosis factor-alpha; TNF-α) levels, and histopathological studies were evaluated in specific brain regions. Results Rats administered ICV-STZ followed by treatment with TF (25, 50, and 100 mg/kg) for 21 days had significantly better mental performance (reduced escape latency to access platform, extended time spent in target quadrant, and improved differential index) in the Morris water maze test and new object recognition test models when compared to control (ICV-STZ)-treated groups. Further, TF treatment significantly restored redox proportion, anti-oxidant levels, regained mitochondrial capacities, attenuated altered AChE action, levels of TNF-α, and histopathological alterations in certain brain regions in comparison with control. In in silico analysis, TF caused greater interaction with NADH dehydrogenase and succinate dehydrogenase. Conclusion The current work demonstrates the neuroprotective ability of TF in an experimental model with AD-like pathologies. The study further suggests that the neuroprotective impacts of TF may be related to its effects on TNF-α levels, oxidative stress pathways, and mitochondrial complex capabilities.

Objective:Patients and their families often ask clinicians to estimate when full-time care (FTC) will be needed after Alzheimer's Disease (AD) is diagnosed. Although a few algorithms predictive algorithms for duration to FTC have been created, these have not been widely adopted for clinical use due to questions regarding precision from limited sample sizes and lack of an easy, user friendly prediction model. Our objective was to develop a clinically relevant, data-driven predictive model using machine learning to estimate time to FTC in AD based on information gathered from a) clinical interview alone, and b) clinical interview plus neuropsychological data.Participants and Methods:The National Alzheimer's Coordinating Center dataset was used to examine 3,809 participants (M age at AD diagnosis = 76.05, SD = 9.76; 47.10% male; 87.20% Caucasian) with AD dementia who were aged >50 years, had no history of stroke, and not dependent on others for basic activities of daily living at time of diagnosis based on qualitative self or informant report. To develop a predictive model for time until FTC, supervised machine learning algorithms (e.g., gradient descent, gradient boosting) were implemented. In Model 1, 29 variables captured at the time of AD diagnosis and often gathered in a clinical interview, including sociodemographic factors, psychiatric conditions, medical history, and MMSE, were included. In Model 2, additional neuropsychological variables assessing episodic memory, language, attention, executive function, and processing speed were added. To train and test the algorithm(s), data were split into a 70:30 ratio. Prediction optimization was examined via cross validation using 1000 bootstrapped samples. Model evaluation included assessment of confusion matrices and calculation of accuracy and precision.Results:The average time to requiring FTC after AD diagnosis was 3.32 years (Range = 0.53-14.57 years). For the clinical interview only model (Model 1), younger age of onset, use of cholinesterase inhibitor medication, incontinence, and apathy were among the clinical variables that significantly predicted duration to FTC, with the largest effects shown for living alone, a positive family history of dementia, and lower MMSE score. In Model 2, the clinical predictors remained significant, and lower Boston Naming Test and Digit-Symbol Coding scores showed the largest effects in predicting duration to FTC among the neuropsychological measures. Final prediction models were further tested using five randomly selected cases. The average estimated time to FTC using the clinical interview model was within an average of 5.2 months of the recorded event and within an average of 5.8 months for the model with neuropsychological data.Conclusions:Predicting when individuals diagnosed with AD will need FTC is important as the transition often carries significant financial costs related to caregiving. Duration to FTC was predicted by clinical and neuropsychological variables that are easily obtained during standard dementia evaluations. Implementation of the model for prediction of FTC in cases showed encouraging prognostic accuracy. The two models show promise as a first step towards creation of a user friendly prediction calculator that could help clinicians better counsel patients on when FTC after AD diagnosis may occur, though the development of separate models for use in more diverse populations will be essential.

Objective:Episodic memory functioning is distributed across two brain circuits, one of which courses through the dorsal anterior cingulate cortex (dACC). Thus, delivering non-invasive neuromodulation technology to the dACC may improve episodic memory functioning in patients with memory problems such as in amnestic mild cognitive impairment (aMCI). This preliminary study is a randomized, double-blinded, sham-controlled clinical trial to examine if high definition transcranial direct current stimulation (HD-tDCS) can be a viable treatment in aMCI.Participants and Methods:Eleven aMCI participants, of whom 9 had multidomain deficits, were randomized to receive 1 mA HD-tDCS (N=7) or sham (N=4) stimulation. HD-tDCS was applied over ten 20-minute sessions targeting the dACC. Neuropsychological measures of episodic memory, verbal fluency, and executive function were completed at baseline and after the last HD-tDCS session. Changes in composite scores for memory and language/executive function tests were compared between groups (one-tailed t-tests with a = 0.10 for significance). Clinically significant change, defined as > 1 SD improvement on at least one test in the memory and non-memory domains, was compared between active and sham stimulation based on the frequency of participants in each.Results:No statistical or clinically significant change (N-1 X2; p = 0.62) was seen in episodic memory for the active HD-tDCS (MDiff = 4.4; SD = 17.1) or sham groups (MDiff = -0.5; SD = 9.7). However, the language and executive function composite showed statistically significant improvement (p = 0.04; MDiff = -15.3; SD = 18.4) for the active HD-tDCS group only (Sham MDiff = -5.8; SD = 10.7). Multiple participants (N=4) in the active group had clinically significant enhancement in language and executive functioning tests, while nobody in the sham group did (p = 0.04).Conclusions:HD-tDCS targeting the dACC had no direct benefit for episodic memory deficits in aMCI based on preliminary findings for this ongoing clinical trial. However, significant improvement in language and executive function skills occurred in response to HD-tDCS, suggesting HD-tDCS in this configuration has promising potential as an intervention for language and executive function deficits in MCI.

Dementia is a functional decline due to cognitive impairment, and its presence is required to make a diagnosis of dementia with Lewy bodies (DLB). Evaluation and management of cognitive impairment in DLB is complex and requires consideration of cognitive fluctuations as well as motor and behavioral symptoms. This article reviews the literature surrounding evaluation and management of cognitive impairment in DLB, highlighting the specific cognitive profile typically seen in early DLB as well as the available evidence for management of these symptoms. There are several pharmacological and nonpharmacological treatment strategies that are currently under investigation, and these are reviewed as well. [Psychiatr Ann. 2022;52(10):404–409.]

Culturally relevant evidence-based interventions for Spanish speaking Latinx care partners are needed to address negative outcomes often associated with caregiver burden. Problem Solving Training (PST), an evidence-based, problem-solving skills training intervention with a person-centered approach is optimal for adaptation to other languages and cultures. Our objective was to culturally adapt PST to Descubriendo Soluciones Juntos (DSJ) for Spanish-speaking Latinx care partners of adults with neurological disorders through and iterative process of translation and language validation and input from therapists and Spanish-speaking Latinx care partners engaged in the intervention. Three primarily Spanish-speaking care partners completed a single-group, pre-post-test design pilot study of DSJ, comprising six one-on-one sessions delivered via telephone or videoconference and baseline and post-intervention measures of caregiver burden, depressive symptoms, and positive aspects of caregiving. Iterative cultural adaptation occurred in concordance with Marsiglia and Booth’s (Res Soc Work Pract 25:423–432, 2015) roadmap for cultural adaptation. Process-based and content-based adaptations are described, resulting in a final protocol for DSJ that maintains the core components of PST. All participants were satisfied with DSJ and reported positive changes in caregiver burden, positive aspects of caregiving, and/or relationship quality with their care recipient. PST/DSJ is a bicultural problem-solving intervention with potential to provide much needed evidence-based support to Spanish-speaking Latinx care partners.

Abstract Background This study examined the extent to which social problem-solving abilities, care situations, and depressive symptomatology were associated with caregiver burden among care partners of adults with Alzheimer’s Disease and Related Dementias (ADRD). Methods Baseline survey data were analyzed from care partners of ADRD who participated in a larger state-funded study. We used validated measures to assess social problem-solving abilities, care situation, positive aspects of caregiving, depressive symptomatology, and caregiver burden. Multivariate regression analysis with backward stepwise entry was used to identify factors associated with caregiver burden. Results Care partners were, on average, age 60.4 (±12.4) and most were female (82.5%) and lived with their care recipient (69.1%). Care partners who reported high caregiver burden were more likely to be male (p< 0.0001) and have a positive problem-solving orientation (p=0.0002), but less likely to have a negative problem-solving orientation (p=0.0376). Higher caregiver burden was also associated with more resentment for caregiving role (p< 0.0001), more anger towards care recipients (p< 0.0001), more depressive symptomology (p< 0.0001), and higher positive aspects of caregiving (p=0.0010). Care partners who reported high caregiver burden also reported less social support (p=0.0076) and less family conflict (p=0.0159). Discussion Findings suggest that factors thought to be protective against caregiver burden may not sufficiently reduce caregiver burden when considering their feelings of resentment and anger towards their care recipient, limited perceived social support, and high depressive symptomology. Interventions to reduce caregiver burden must consider care partners’ internal conflict as a caregiver and the relationship between the care partner and their care recipient.

Osteoporosis characterized by decrease in bone mass, is a major health problem affecting 2 in 3 women in postmenopausal years. Traditional therapies for post menopausal osteoporosis have emphasized the use of anti-resorption agents such as estrogen, calcitonin and bisphosphonates. Although these agents may prevent further bone loss in established osteoporosis, they cannot restore bone mass that has been lost already. Also some women are reluctant to take estrogen replacement therapy because of potentially increased cancer risks. Thus it is necessary to develop naturally occurring compounds or synthetic substances with less undesirable side effects that can substitute or reduce the need for drugs used currently.Resveratrol is a plant polyphenol that was shown to have beneficial effects of estrogen. While extensive data on mechanism of resveratrol’s protective effects against cardiovascular diseases and cancer is available its effect on bone metabolism is poorly understood. Thus it is important to study the effects of resveratrol on factors involved in bone remodeling and this will lead to the identification of molecular targets for designing of drugs that can be used to prevent osteoporosis. Resveratrol is considered to be a promising therapeutic for all the postmenopausal health problems. The molecular mechanism involved in osteoprotective effect of resveratrol has not even been interrogated. As such the number of studies that have reported the osteoprotective effect of resveratrol are scanty.So the present study was conducted to investigate the molecular mechanisms of protection conferred by resveratrol against estrogen deficiency induced osteoporosis, using surgical menopause model of rat. The study was conducted on three months old Sprague Dawley (SD) rats which were given resveratrol (0.7 and 5mg per Kg diet) for 1 month. The rats were randomly divided into six study groups each comprising 7 animals each, (i) sham operated control group(ii) ovariectomized (hi) ovariectomized treated with (β-estradiol (3.9mg/kg diet) (iv) sham operated treated with resveratrol (0.7mg/Kg diet) (v) ovariectomized treated with resveratrol (0.7 mg/Kg diet) (vi) ovariectomized treated with resveratrol (5 mg/Kg diet).At the end of 1 month , blood was collected to estimate serum osteoclastic and osteoblastic parameters. Femur was also removed and its proximal end was used to extract RNA and protein. Quantitative analysis of estrogen receptor α, β, vitamin D receptor (VDR), parathyroid hormone receptor was done at gene and protein levels in all the groups. Proinflammatory cytokines (IL-1β and TNF-α) were also checked in proximal end of the femur. Tibia was removed to analyze density, calcium, phosphorous and mineral content in the bone.Our study showed improvement in physiological and biochemical profile of ovariectomized animals when treated with resveratrol in dose dependent manner. Concomitant with the decrease in the levels of osteoporotic markers in resveratrol treated animals as compared to ovariectomized animals we observed an increase in the expression of ER-α, ER-β and VDR in resveratrol treated animals. The expression levels of PTHR which is an osteoclastic factor, decreased in experimental animals as compared to control animals. There was also decrease in cytokine levels when ovariectomized animals were treated with resveratrol.Hence our study can show that resveratrol has protective role in curing osteoporosis caused by estrogen deficiency by directly affecting the expression of critical factors involved in bone remodelling.