SEARCH · PubMed Health

Results for “Cognitive Dysfunction”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources

PubMed1998

Measuring health status in older patients. The SF-36 in practice.

OBJECTIVE: To examine the use of the Medical Outcomes Study short form 36-item (SF-36) health status measure in older patients receiving health care; to explore the influence of age and physical and cognitive status on response to and completion of the SF-36 questionnaire. DESIGN: Prospective observational study. SETTINGS: Hospital and ambulatory patients aged 65 years and over in the medical and surgical wards and outpatient department of a teaching hospital and a local general practitioner's surgery. SUBJECTS: 1014 hospital inpatients, 80 hospital outpatients and 40 patients attending their general practitioner's surgery. MAIN OUTCOME MEASURES: Response rates, overall rates of completion (sufficient to calculate a valid SF-36 score) and completion of individual questions. RESULTS: 37 out of 40 ambulatory patients in general practice (93%) and 71 out of 80 outpatients (89%) returned a self-completed questionnaire. In hospital inpatients the overall response rate was only 46% (369 of 802). This was improved by interview administration to 77.4% (164 of 212). Logistic regression analysis revealed that self-completion, cognitive dysfunction, disability and age were all independently associated with poor overall response rates. Among those patients who returned a completed questionnaire, completion of individual questions sufficient to calculate a valid score was variable. Only 62.5% of inpatients who self-completed a questionnaire gave sufficient response to calculate a score on the mental health subscale, compared with 93.7% of general practice patients. CONCLUSION: The self-administered questionnaire is unacceptable for older hospital inpatients. Use of an interviewer improves response, but factors which influence health status, such as physical and cognitive dysfunction, have a significant effect on response rates. Therefore the utility of the SF-36 in its present form as a routine health status measure for use in older hospital inpatients is questioned.

Aged↗

PubMedDate not supplied

Religion, senescence, and mental health: the end of life is not the end of hope.

The authors review epidemiological and survey research relevant to the relationships between religiousness/spirituality and mental health in people at the end of life, with the end of helping psychiatrists, psychologists, and other mental health professionals dealing with older Americans. They give special attention to well-being, religious coping, cognitive dysfunction, anxiety, depression, and suicide, and consider the extent to which hope is a mediator of the purported salutary effects of religiousness. Studies were selected from the comprehensive and systematic review of 20th-century scientific literature concerning religion and health. Authors also review current studies relevant to religion and end-of-life issues. Religious persons reported generally higher levels of well-being. The review also found fairly consistent inverse associations of religiousness with rates of depression and suicide. There was some negative association between religious participation and cognitive dysfunction, but the association with anxiety was inconsistent, with some studies showing a correlation between higher levels of religion and anxiety. Religion's effects on mental health are generally protective in direction but modest in strength.

Adaptation, Psychological↗

PubMed2006

Can care of elderly be measured? A method for estimating the individual care of recipients in community health care.

BACKGROUND: Almost every country in the Western world has great difficulties allocating enough financial resources to meet the needs in the care of the increasing elderly population. The main problem is common to all countries and concerns the efforts to meet elderly persons' needs on an individual level while still maintaining society's responsibility for distributing justice. The aim of this study is to elaborate an instrument for measuring the quality of individual care and staff's working time in order to allocate public resources fairly. The present study gives an account of a new classification system named TiC (Time in Care), indicating how it can be used most effectively and also investigating the validity and reliability of the system. METHODS: All recipients in 13 sheltered homes for elderly care (n = 505) in a Swedish municipality were surveyed regarding the care they needed, in dimensions of General Care, Medical Care, Cognitive Dysfunction and Rehabilitation, and the time required. Construct validity was assessed by means of factor analysis. The inter-rater agreement of two raters concerning 79 recipients was measured using weighted Kappa. The stability of the instrument and its sensitivity to change were investigated through test-retest reliability measurements, conducted once a month during a six-month period. The content validity of the instrument was also assessed. RESULTS: Factor analysis resulted in a reduction of the number of items from 25 to 16 in three dimensions: General Care, Medical Care and Cognitive Dysfunction. The Kappa analysis showed satisfactory to excellent inter-rater agreement. The care need scores were basically stable but showed sensitivity to change in health status. CONCLUSION: The instrument was found to be useful and reliable for assessing individual needs in community health care.

Aged↗

PubMed2002

[Irrational attitudes and social stress in outpatient behavior therapy: changes, prognostic and mediating influences].

UNLABELLED: Various studies suggest that social stress and cognitive dysfunction contribute to the development of psychiatric disorders. Their roles as moderators and mediators of recovery have rarely been studied. Aim of the present research was to investigate 1. the change of irrational attitudes and perceived social stress during outpatient behavioral treatment and their contribution to 2. the prediction and 3. mediation of success in patients with heterogeneous diagnoses. METHODS: A diagnostically unselected sample of 62 outpatients participated in a questionnaire study at the beginning and at the end of treatment. Success of treatment was assessed by the Symptom Check-List-90-R. Cognitive dysfunction was measured by the Irrational Attitudes Questionnaire (IAQ). Instruments for the assessment of perceived social stress were the Scale of Recent Life Events (SRL), the Contractual Conditions-Scale (CCS) and the Impact of Event-Scale (IES). RESULTS: 1. Psychological symptoms, irrational attitudes and perceived social stress decreased during therapy, while the number of life events remained constant. 2. Clinically reliably changed patients scored higher in Self-Blame (IAQ) than non-responders at the beginning of therapy. 3. The reduction of Negative Self-Evaluation (IAQ) was stronger in patients with clinical change than in unchanged patients. DISCUSSION: The results were disputed with reference to the literature and to limitations of the study.

Adolescent↗

PubMed2002

High incidence of mental disorders, reduced mental well-being and cognitive function in hypopituitary women with GH deficiency treated for pituitary disease.

OBJECTIVE: Previous studies have shown possible neuroendocrine effects of GH. In the present study we investigated the incidence of mental disorders and the prevalence of mental distress and cognitive dysfunction in hypopituitary women with untreated GH deficiency compared to population-based controls. DESIGN AND PATIENTS: Thirty-three hypopituitary women with a median age of 64 years (range 39--77 years) were investigated cross-sectionally, without any change in hormone substitutions. Twenty-nine of the patients had been operated for a pituitary tumour, 25 had received radiotherapy and 15 had visual dysfunction. The patients were with a very high probability GH deficient, as 29 had subnormal IGF-I levels and the other four were GH deficient as assessed by an insulin tolerance test. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence. MEASUREMENTS: The incidence of mental disorders was calculated from the date of diagnosed hypopituitarism to the time of the present investigation. Mental well-being was assessed by three self-rating questionnaires: the Symptom Checklist-90 (SCL-90), the Interview Schedule for Social Interaction (ISSI) and the social network concept. The subjects were examined with neuropsychological tests of vocabulary (SRB:1 vocabulary test), perceptual speed (WAIS-R Digit Symbol), spatial ability (WAIS-R Block Design), verbal memory (Cronholm--Molander verbal memory test), spatial learning (Austin Maze Test) and reaction time (APT Two-way Reaction Time and APT Inhibition). RESULTS: The hypopituitary women had a higher incidence of mental disorders than the controls; Incidence Rate Ratio 4.5 (95% CI 1.0--21). The Global Severity Index, i.e. the average score of all 90 questions of the SCL-90, was higher in patients (P = 0.001), and the patients had significantly more symptoms of somatization, anxiety, depression, obsession--compulsion, hostility--irritability, phobic and psychotic symptoms (all P less-than-or-equal 0.04). Moreover, 14 patients compared to four controls were classified as possible cases of mental distress according to the SCL-90 (P = 0.006). The patients experienced lower availability of both social attachment (P = 0.02) and integration (P = 0.001), but there were no group differences in the adequacy of these dimensions or in emotional support. The patients had lower scores in four of seven neuropsychological tests (all P less-than-or-equal 0.04). CONCLUSIONS: The hypopituitary women had a higher incidence of mental disorders, more symptoms of mental distress and increased prevalence of cognitive dysfunction. The impaired results in the patients could possibly be explained by several factors, such as transfrontal surgery, radiotherapy, visual dysfunction and unphysiological hormone substitution. Moreover, it is probable that GH deficiency contributed, but placebo-controlled double-blind studies are warranted to investigate whether the psychological dysfunction is reversible on GH substitution.

Adult↗

PubMed2001

Neuropsychiatric manifestations and their clinical associations in southern Chinese patients with systemic lupus erythematosus.

OBJECTIVE: To study the neuropsychiatric (NP) manifestations in a large cohort of southern Chinese patients with systemic lupus erythematosus (SLE) according to the new 1999 American College of Rheumatology (ACR) case definitions and their clinical associations. METHOD: Patients with SLE who were followed from 1984 to 2000 were retrospectively reviewed. Patients with NP manifestations were ascertained and classified by at least 2 rheumatologists, with the collaboration of neurologists and psychiatrists. The association of NP manifestations with other clinical features and autoantibodies was studied by statistical analysis. RESULTS: Five hundred eighteen patients with SLE were studied. The female to male ratio was 7.8 to 1 and the mean age of disease onset was 29.5 +/- 12.0 years (range 9-80). The mean duration of followup was 7.3 +/- 6.7 years (range 0.3-23.0). Ninety-six patients (19%) had 133 NP events and the mean number of events per patient-year of followup was 0.035. In decreasing order of frequency. these events were: seizure disorder (28%), cerebrovascular disease (19%), acute confusional state (14%), psychosis (11%), myelopathy (8%), mood disorder (6%), headache (4%), movement disorder (2%), cranial neuropathy (3%), demyelinating syndrome (1.5%), anxiety disorder (1.5%), mononeuritis multiplex/mononeuropathy (1.5%), aseptic meningitis (1%), and polyneuropathy (1%). Cognitive dysfunction was not classified because of the lack of standard neuropsychological testing for every patient. Univariate analysis revealed that NP-SLE was associated with a positive lupus anticoagulant (LAC) (p = 0.001), a strongly positive IgG anticardiolipin (aCL) (p = 0.01). leukopenia (p = 0.01), lymphopenia (p = 0.03), thrombocytopenia (p = 0.03), and pulmonary involvement (p = 0.03). Multivariate analysis showed that a strongly positive IgG aCL [RR 3.1 (1.3-7.7), p = 0.01] and a history of cyclophosphamide treatment [RR 4.3 (2.1-9.0), p < 0.001] were independently associated with NP manifestations in our cohort. Among the NP features, cerebrovascular disorder was particularly associated with the presence of LAC [OR 3.3 (1.4-8.0), p = 0.01] and a strongly positive IgG aCL [OR 3.1 (1.1-8.2), p = 0.031]. CONCLUSION: The point prevalence of overt NP manifestations in our cohort of patients with SLE was 19%. This percentage was likely higher if subtle cognitive dysfunction was included. Seizure and cerebrovascular disorders were the most common NP features. The presence of antiphospholipid antibodies was significantly associated with NP manifestations, especially cerebrovascular disorders.

Adolescent↗

PubMed2006

The influence of cognitive function on outcome after a hip fracture.

BACKGROUND: Previous studies have indicated that patients with a hip fracture who have impaired cognitive function have an increased risk for complications, poor long-term outcome, and an increased mortality rate. An assessment of cognitive function is often lacking in nursing and medical records. We investigated whether an assessment of cognitive function obtained with use of a validated instrument would be a useful patient management adjunct. METHODS: We studied 213 patients with a hip fracture who had a mean age of eighty-four years and were entered in a prospective trial with a follow-up evaluation at four and twelve months. On admission to the orthopaedic ward, the patients were evaluated with use of the Short Portable Mental Status Questionnaire to assess their cognitive function. The outcome for patients with severe cognitive dysfunction, i.e., those with a score of <3 on the questionnaire, was compared with the outcome for patients with higher scores. The main outcome measurements were the Charnley hip score, activities of daily living status, health-related quality of life, and mortality. RESULTS: A Short Portable Mental Status Questionnaire score of <3 and male gender were associated with an increased mortality rate during the first twelve months. Moreover, patients with a score of <3 had a significantly worse outcome with regard to the ability to walk and to perform the activities of daily living, with 36% of these patients confined to a wheelchair and almost 39% totally dependent with regard to daily living functions at the time of the final follow-up (p < 0.001). CONCLUSIONS: The systematic use of the Short Portable Mental Status Questionnaire upon admission to the orthopaedic ward identifies patients with a hip fracture who have severe cognitive dysfunction and effectively predicts their outcome with regard to the ability to walk, ability to perform the activities of daily living, and mortality, and it can be recommended for use in the care of elderly patients with a hip fracture.

Aged↗

PubMed1998

Negative attributional style in seasonal and nonseasonal depression.

OBJECTIVE: There is a substantial relationship between dysfunctional cognitions and the clinical course of major depression. This study examined whether this association extends to patients with seasonal affective disorder. METHOD: A revised version of the Attributional Style Questionnaire was used to assess negative attributional style and predict response to treatment in a group of depressed outpatients, 26 with seasonal depression and 30 with nonseasonal, unipolar major depression. RESULTS: Pretreatment scores on negative attributional style did not differ between the patients with seasonal affective disorder and those with nonseasonal depression. Negative attributional style predicted poor response to pharmacotherapy in the nonseasonal depression group but did not predict response to light therapy in the group with seasonal affective disorder. CONCLUSIONS: Dysfunctional cognitions may play a lesser role in seasonal affective disorder than in nonseasonal depression.

Adult↗

PubMed1994

A clinical and laboratory profile of symptomatic women with silicone breast implants.

One hundred seventy-six patients with breast prosthetic implants were evaluated. All women were symptomatic and were referred by either attorneys (152) or physicians (24) for rheumatic evaluation. The women ranged in age from 24 to 72 with a mean of 45 years. Indications for surgery were cosmetic (128), cancer (34), and other (14). Implants had been in place for 7 years or more in 120 patients and < 2 years in only 8. Eighty-three women required explantation of their original prostheses, and 63 had new implants inserted of which 47 were silicone and 16 were saline. Capsular contractures were present in 128 women, and documented implant rupture occurred in 67. Sixty-four women underwent manual closed capsulotomies. Of the 63 revisions, 37 resulted in contractures of the new implant. The most frequent symptoms seen in the women were chronic fatigue (77%) cognitive dysfunction (65%), arthralgia (56%), dry mouth (53%), dry eye (50%), alopecia (40%), and dysphagia (35%). The most common findings on physical examination were telangiectasias (60%), erythema of the chest wall (56%), carpal tunnel syndrome (47%), petechiae (46%), lacrimal gland enlargement (26%), thyroid tenderness (22%), thyroid enlargement (21%), and parotid enlargement (18%). Laboratory findings included elevated cholesterol (59%), elevated erythrocyte sedimentation rate (32%), elevated serum immunoglobulin (28%), and positive autonuclear antibody (25%) seen most often. Despite clinical features suggesting Sjögren's syndrome, antibodies to Ro (SSA) were seen in only 2 patients, and antibodies to La (SSB) were seen in only 4 patients. Siliconosis is a novel systemic disease with symptoms of chronic fatigue, cognitive dysfunction, sicca syndrome, and arthralgia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2007

[Immunology in schizophrenic disorders].

This manuscript deals with whether immune-mediated mechanisms of inflammation contribute to the pathogenesis of schizophrenia. A model is presented which integrates psychoneuroimmunologic findings and actual results from pharmacological, neurochemical, and genetic studies in schizophrenia. A pivotal role in the neurobiology of schizophrenia is played by dopaminergic neurotransmission, which is modulated by influences of the glutamatergic system. The decreased function of the glutamate system described in schizophrenia seems primarily mediated by N-methyl-D-aspartate (NMDA) receptor antagonism. Kynurenine acid is the only known endogenous NMDA receptor antagonist. In higher concentrations it blocks the NMDA receptor, but in lower concentrations it blocks the nicotinergic acetylcholin receptor, which has a prominent role in cognitive functions. Therefore, higher levels of kynurenine acid may explain psychotic symptoms and cognitive dysfunction. Several findings point out that prenatal infection, associated with an early sensitisation of the immune system, may result in an imbalance of the immune response (type 1 vs type 2) in schizophrenia. This immune constellation leads to inhibition of the enzyme indoleamin dioxigenase (IDO). It and tryptophane 2,3-dioxygenase (TDO) both catalyse the degradation from tryptophan to kynurenine. Due to the inhibition of IDO, tryptophan is metabolised to kynurenine primarily by TDO. In the CNS, TDO is located only in astrocytes, which are in particular activated in schizophrenia and in which kynurenine acid is the final product and can not be further metabolised. Therefore kynurenine acid accumulates in the CNS of schizophrenics and - due to its NMDA-antagonistic properties - leads to cognitive dysfunction and psychotic symptoms. This model describes the pathway of immune-mediated glutamatergic-dopaminergic dysregulation, which may lead to the clinical symptoms of schizophrenia. Therapeutic consequences (e.g. cyclo-oxygenase-2 inhibitors) are discussed.

Brain↗

PubMed2006

Absence of synaptophysin near cortical neurons containing oligomer Abeta in Alzheimer's disease brain.

Soluble amyloid beta protein (Abeta) oligomers have been considered recently to be responsible for the cognitive dysfunction that sets in prior to senile plaque formation in the Alzheimer's disease (AD) brain. By using the newly prepared antibody against oligomer Abeta, rather than fibrillar or monomer Abeta, we observed that oligomer Abeta in AD brains was localized as clusters ofdot-likeimmunostains in the neurons in a manner different from that in senile plaques. The relationship of oligomer Abeta with synaptophysin, a synaptic molecular marker, was examined because oligomer Abeta is widely believed to be related to synaptic failure. We observed that immunostainings for synaptophysin were absent near neurons bearing clusters of oligomer Abeta. The present study provides morphological evidence to support the idea that accumulated oligomer Abeta, but not fibrillar Abeta, is closely associated with synaptic failure, which is the major cause of cognitive dysfunction.

Alzheimer Disease↗

PubMed1997

[Information processing deficits in depression in terms of event-related potentials: in comparison with schizophrenics and normal controls].

Information processing deficits characteristic of remitted major depression, which may be a vulnerability marker for the disease, were examined from two aspects by means of visual event-related potentials (ERPs) obtained during simple and discriminative response tasks: 1. To clarify the difference in cognitive dysfunction between both depressives and schizophrenics in remission, we compared the ERPs in remitted depressive patients (n = 11) and remitted schizophrenic patients (n = 9) with those of age, and sex-matched controls (n = 10). 2. To clarify the influence of aging on information processing in remitted depression, ERPs in young remitted depressives (20-46 years old, n = 11) were compared with those in older remitted depressives (52-75 years old, n = 11) in contrast to young (n = 10) and older (n = 11) controls. The remitted schizophrenics showed a retardation in NA and N2 latencies and a reduction in P3 amplitude. However, P1 increased in amplitude exclusively in the remitted depressives. The effect of stimulus discrimination on N1 seen in the controls was absent in both patient groups. The results suggest that the remitted depressives had an attentional deficit in early information processing reflected on P1 and N1 potentials, while the remitted schizophrenics had an extensive cognitive dysfunction reflected on N1, NA, N2, and P3 potentials. Although the effect of stimulus discrimination on N1 was absent in both young and older remitted depressive patients, older patients showed no effects of normal aging on ERPs such as P1 increase or N1 increase during discrimination tasks. Significant interaction effects between diagnosis and aging were found by ANOVA only in the laterality of the P1 amplitude. Older remitted depressives showed an unbalanced right-predominance in P1 amplitude. These results suggest that older remitted depressives had the same early information-processing deficit seen in the young remitted depressives as well as an overactivation over the right hemisphere in the attentional mechanism, irrespective of normal aging.

Adult↗

PubMed1984

Cranial electrotherapy stimulation treatment of cognitive brain dysfunction in chemical dependence.

Several studies have shown that cranial electrotherapy stimulation (CES) is useful in treating brain dysfunction associated with alcoholism. A double-blind study replicated the latest of these findings in 60 inpatients and extended them by treating individuals with alcoholism and other chemical dependencies. Treatment effects were assessed on three subscales of the WAIS that are clinical indicators of organic brain syndrome. No placebo effect was found. CES appears to be a valuable adjunct to rehabilitation programs for addicted persons and can effect changes in areas not addressed by other treatment modalities.

Adult↗

PubMed2002

Titration of isoflurane using BIS index improves early recovery of elderly patients undergoing orthopedic surgeries.

PURPOSE: This study was designed to investigate the effect of bispectral index (BIS) monitoring on the recovery profiles, level of postoperative cognitive dysfunction, and anesthetic drug requirements of elderly patients undergoing elective orthopedic surgery with general anesthesia. METHODS: Sixty-eight patients over the age of 60 were randomized into one of two groups. In the standard practice (SP) group, the anesthesiologists were blinded to the BIS value, and isoflurane was titrated according to standard clinical practice. In the BIS group, isoflurane was titrated to maintain a BIS value between 50-60. RESULTS: The total isoflurane usage was 30% lower in the BIS group compared to the SP group (5.6 +/- 3 vs 7.7 +/- 3 mL, P <0.05). The time to orientation was faster in the BIS group compared to the SP group (9.5 +/- 3 vs 13.1 +/- 4 min, P <0.001). There were no differences in the postoperative psychometric tests between the two groups. CONCLUSIONS: There was no difference in the level of postoperative cognitive dysfunction between the two groups. However, titration of isoflurane using the BIS index decreased utilization of isoflurane and contributed to faster emergence of elderly patients undergoing elective knee or hip replacement surgery.

Aged↗

PubMed2003

Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory.

Amyloid-beta precursor protein (APP) is a membrane-spanning protein with a large extracellular domain and a much smaller intracellular domain. It is the source of the amyloid-beta (Abeta) peptide found in neuritic plaques of Alzheimer's disease (AD) patients. Because Abeta shows neurotoxic properties, and because familial forms of AD promote Abeta accumulation, a massive international research effort has been aimed at understanding the mechanisms of Abeta generation, catabolism and toxicity. APP, however, is an extremely complex molecule that may be a functionally important molecule in its full-length configuration, as well as being the source of numerous fragments with varying effects on neural function. For example, one fragment derived from the non-amyloidogenic processing pathway, secreted APPalpha (sAPPalpha), is neuroprotective, neurotrophic and regulates cell excitability and synaptic plasticity, while Abeta appears to exert opposing effects. Less is known about the neural functions of other fragments, but there is a growing interest in understanding the basic biology of APP as it has become recognized that alterations in the functional activity of the APP fragments during disease states will have complex effects on cell function. Indeed, it has been proposed that reductions in the level or activity of certain APP fragments, in addition to accumulation of Abeta, may play a critical role in the cognitive dysfunction associated with AD, particularly early in the course of the disease. To test and modify this hypothesis, it is important to understand the roles that full-length APP and its fragments normally play in neuronal structure and function. Here we review evidence addressing these fundamental questions, paying particular attention to the contributions that APP fragments play in synaptic transmission and neural plasticity, as these may be key to understanding their effects on learning and memory. It is clear from this literature that APP fragments, including Abeta, can exert a powerful regulation of key neural functions including cell excitability, synaptic transmission and long-term potentiation, both acutely and over the long-term. Furthermore, there is a small but growing literature confirming that these fragments correspondingly regulate behavioral learning and memory. These data indicate that a full account of cognitive dysfunction in AD will need to incorporate the actions of the full complement of APP fragments. To this end, there is an urgent need for a dedicated research effort aimed at understanding the behavioral consequences of altered levels and activity of the different APP fragments as a result of experience and disease.

Alzheimer Disease↗

PubMed2002

Behavioral and neurological correlates of ALS-parkinsonism dementia complex in adult mice fed washed cycad flour.

Consumption of cycad seed products (Cycas circinalis) is one of the strongest epidemiological links to the Guamian neurological disorder amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), however, the putative toxin which causes neurodegeneration has never been identified definitively. To reexamine this issue, 6-7-mo-old, male CD-1 mice were assessed for motor and cognitive behaviours during and following feeding with pellets made from washed cycad flour. Cycad-fed animals showed early evidence of progressive motor and cognitive dysfunctions. Neurodegeneration measured using TUNEL and caspase-3 labeling was found in neocortex, various hippocampal fields, substantia nigra, olfactory bulb, and spinal cord. In vitro studies using rat neocortex have identified toxic compounds in washed cycad flour that induce depolarizing field potentials and lead to release of lactate dehydrogenase (LDH), both blocked by AP5. High-performance liquid chromatography (HPLC)/mass spectrometry of cycad flour samples failed to show appreciable amounts of other known cycad toxins, cycasin, MAM, or BMAA; only trace amounts of BOAA were present. Isolation procedures employing these techniques identified the most toxic component as beta-sitosterol beta-D-glucoside (BSSG). The present data suggest that a neurotoxin, or a toxic metabolite, not previously identified in cycad, is able to gain access to central nervous system (CNS) resulting in neurodegeneration of specific neural populations and in motor and cognitive dysfunctions. These data are consistent with a number of major features of ALS-PDC in humans.

Amyotrophic Lateral Sclerosis↗

PubMed2026

Downregulation of Trpv4 and Klf2 in brain microvessels is associated with the progression of neurovascular dysfunction and cognitive impairment in a model of heart failure with preserved ejection fraction.

Vascular cognitive impairment (VCI) shares major risk factors with heart failure with preserved ejection fraction (HFpEF), including obesity, diabetes and hypertension. Yet VCI research often relies on single-stimulus models, whereas patients experience combined risk factors. We therefore assessed cerebrovascular and cognitive phenotypes in an HFpEF model and investigated underlying mechanisms. Male Lean and Obese ZSF1 rats underwent longitudinal assessments of blood pressure, glucose, cardiac function and behavioural performance. Cerebral blood flow and neurovascular coupling were assessed by laser speckle contrast imaging. White matter integrity, blood-brain barrier (BBB) permeability and vascular density were analyzed by (immuno)histochemistry. Cortical microvessels were isolated for transcriptomic profiling, and selected targets were validated using multiplex in-situ hybridization. Obese rats exhibited neurovascular uncoupling and impaired short- and long-term memory and spatial learning, accompanied by brain atrophy and reduced myelin. BBB permeability increased at 22-23 weeks and vascular density at 34-35 weeks in Obese versus Lean rats. Transcriptomic analysis of brain microvessels revealed altered processes related to angiogenesis, vasoreactivity, immune mechanisms and vascular remodelling, with consistent downregulation of Trpv4 and Klf2. Obese ZSF1 rats develop progressive neurovascular dysfunction associated with HFpEF onset and reduced Trpv4 and Klf2 expression in cerebral microvessels, two key vasoprotective genes.

Diastolic dysfunction↗

PubMed2000

Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas.

Siotone (ST) is a herbal formulation comprising of Withania somnifera, Ocimum sanctum, Asparagus racemosus, Tribulus terristris and shilajit, all of which are classified in Ayurveda as rasayanas which are reputed to promote physical and mental health, improve defence mechanisms of the body and enhance longevity. These attributes are similar to the modern concept of adaptogenic agents, which are, known to afford protection of the human physiological system against diverse stressors. The present study was undertaken to investigate the adaptogenic activity of ST against chronic unpredictable, but mild, footshock stress induced perturbations in behaviour (depression), glucose metabolism, suppressed male sexual behaviour, immunosuppression and cognitive dysfunction in CF strain albino rats. Gastric ulceration, adrenal gland and spleen weights, ascorbic acid and corticosterone concentrations of adrenal cortex, and plasma corticosterone levels, were used as the stress indices. Panax ginseng (PG) was used as the standard adaptogenic agent for comparison. Additionally, rat brain levels of tribulin, an endogenous endocoid postulated to be involved in stress, were also assessed in terms of endogenous monoamine oxidase (MAO) A and MAOB inhibitory activity. Chronic unpredictable footshock induced marked gastric ulceration, significant increase in adrenal gland weight and plasma corticosterone levels, with concomitant decreases in spleen weight, and concentrations of adrenal gland ascorbic acid and corticosterone. These effects were attenuated by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.), administered once daily over a period of 14 days, the period of stress induction. Chronic stress also induced glucose intolerance, suppressed male sexual behaviour, induced behavioural depression (Porsolt's swim despair test and learned helplessness test) and cognitive dysfunction (attenuated retention of learning in active and passive avoidance tests), and immunosuppression (leucocyte migration inhibition and sheep RBC challenged increase in paw oedema in sensitized rats). All these chronic stress-induced perturbations were attenuated, dose-dependently by ST (50 and 100 mg/kg, p.o.) and PG (100 mg/kg, p.o.). Chronic stress-induced increase in rat brain tribulin activity was also reversed by these doses of ST and by PG. The results indicate that ST has significant adaptogenic activity, qualitatively comparable to PG, against a variety of behavioural, biochemical and physiological perturbations induced by unpredictable stress, which has been proposed to be a better indicator of clinical stress than acute stress parameters. The likely contribution of the individual constituents of ST in the observed adaptogenic action of the polyherbal formulation, have been discussed.

Animals↗