Search

Background and purpose: Idiopathic normal pressure hydrocephalus (iNPH) is a chronic neurological disease resulting in progressive gait and cognitive disorders. We investigated whether the gait phenotype is associated with the severity of cognitive deficits in iNPH. Methods: This retrospective study recruited 88 patients (mean age = 76.18 ± 7.21 years, 42% female). Patients were initially referred for suspicion of iNPH and underwent a comprehensive analysis, including gait analysis and cognitive evaluation. Results: In this cohort (27% normal gait, 25% frontal gait, 16% parkinsonian gait, 27% other gait abnormalities), patients with parkinsonian and frontal gait had the lowest Mini‐Mental State Examination (MMSE) scores and the slowest gait speed. Patients with normal gait had the highest MMSE scores and gait speed. Frontal gait was associated with lower MMSE score, even after adjusting for age, gender, comorbidities, white matter lesions, and education level (β = −0.221 [95% confidence interval (CI) = −3.718 to −0.150], p = 0.034). Normal gait was associated with the best MMSE scores, even after adjusting for the abovementioned variables (β = 0.231 [95% CI = 0.124–3.639], p = 0.036). Conclusions: Gait phenotypes among iNPH patients are linked to global cognition as assessed with MMSE. [ABSTRACT FROM AUTHOR]

Postoperative cognitive dysfunction (POCD) is a major concern, particularly among older adults. This study used social isolation (ISO) and multiomics analyses in aged mice to investigate potential mechanisms underlying POCD development. Aged mice were divided into two groups: ISO and paired housing (PH). Oleamide and the cannabinoid receptor type 2 (CB2R) antagonist AM630 were administered intraperitoneally, while Foxq1 adeno‐associated viral (AAV) vector was injected directly into the hippocampus. Intramedullary tibial surgeries were subsequently performed to establish the POCD models. Behavioral tests comprising the Y‐maze, open field test, and novel object recognition were conducted 2 days after surgery. Hippocampal and serum inflammatory cytokines were assessed. Following surgery, ISO mice demonstrated intensified cognitive impairments and escalated inflammatory markers. Integrative transcriptomic and metabolomic analysis revealed elevated oleamide concentrations in the hippocampus and serum of PH mice, with associative investigations indicating a close relationship between the Foxq1 gene and oleamide levels. While oleamide administration and Foxq1 gene overexpression substantially ameliorated postoperative cognitive performance and systemic inflammation in mice, CB2R antagonist AM630 impeded these enhancements. The Foxq1 gene and oleamide may be crucial in alleviating POCD. While potentially acting through CB2R‐mediated pathways, these factors may modulate neuroinflammation and attenuate proinflammatory cytokine levels within the hippocampus, substantially improving cognitive performance postsurgery. This study lays the groundwork for future research into therapeutic approaches targeting the Foxq1‐oleamide‐CB2R axis, with the ultimate goal of preventing or mitigating POCD. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions.International experts in cognitive disorders were invited to assess seven illustrative clinical vignettes containing history and bedside characteristics alone. Participants assigned a probable diagnosis and selected the appropriate investigation and treatment. Qualitative, quantitative and inter‐rater agreement analyses were undertaken.Eighteen diagnostic terminologies were assigned by 45 cognitive experts from 12 countries with a median of 13 years of experience, across the seven scenarios. Accurate discrimination between FCD and neurodegeneration was observed, independently of background and years of experience: 100% of the neurodegenerative vignettes were correctly classified and 75%–88% of the FCD diagnoses were attributed to non‐neurodegenerative causes. There was <50% agreement in the terminology used for FCD, in comparison with 87%–92% agreement for neurodegenerative syndromes. Blood tests and neuropsychological evaluation were the leading diagnostic modalities for FCD. Diagnostic communication, psychotherapy and psychiatry referral were the main suggested management strategies in FCD.Our study demonstrates the feasibility of distinguishing between FCD and neurodegeneration based on relevant patient characteristics and history details. These characteristics need further validation and operationalisation. Heterogeneous labelling and framing pose clinical and research challenges reflecting a lack of agreement in the field. Careful consideration of FCD diagnosis is advised, particularly in the presence of comorbidities. This study informs future research on diagnostic tools and evidence‐based interventions. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is high in the elderly population and seriously affects the quality of life. Brain‐derived neurotrophic factor (BDNF) is one of the key neurotrophic proteins, and activation of BDNF–TrkB is considered an effective strategy to improve cognitive dysfunction during aging. In this study, administration of polygonatum sibiricum (PS) for 5 months effectively ameliorates the cognitive function, improving the Nissl body state in cortex and hippocampus in aging rats. In addition, PS can improve the synaptic structure and increase the number of synapses. Furthermore, PS reverses the reduction of synaptic plasticity‐related proteins postsynaptic density protein 95 (PSD‐95) and synaptophysin during aging and up‐regulates the expression of BDNF–TrkB. In conclusion, PS improves cognitive dysfunction and enhances synaptic plasticity in naturally aged rats by regulating the BDNF–TrkB signaling pathway. PS has the potential to be developed as a novel and promising functional health food for the elderly. Practical applications: Polygonatum sibiricum (PS) is a traditional Chinese medicine, which has been included in the homologous plant of medicine and food. PS has been widely used to treat lung diseases, diabetes and antiaging in clinical. Studies have confirmed that PS can accelerate the repair and regeneration of damaged neurons, reverse the changes in synaptic structure, and improve the ability of learning and memory. Our study confirmed that PS significantly improved the cognitive function in aging rats. PS has great potential to be developed as a functional food for improving neurological function and anti‐aging. [ABSTRACT FROM AUTHOR]

Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long‐term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long‐term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives. [ABSTRACT FROM AUTHOR]

Mild parkinsonian signs (MPS) have been widely studied during the past 3 decades and proposed as a risk marker for neurodegenerative disease. This systematic review explores the epidemiology, clinical and prognostic associations, radiological features, and pathological findings associated with MPS in older adults free from neurodegenerative disease. We find that MPS as currently defined are strongly associated with increasing age and increased risk of development of Parkinson's disease (PD), all‐cause dementia, disability, and death. Positive associations with later PD are found mainly in younger populations and those with other features of prodromal PD. There are currently no consistent radiological findings for MPS, and pathological studies have shown that MPS, at least in the oldest old, are often underpinned by mixed neuropathologies, including those associated with Alzheimer's disease, cerebrovascular disease, nigral neuronal loss, and Lewy bodies. Different subcategories of MPS appear to convey varying risk and specificity for PD and other outcomes. MPS overall are not specific for parkinsonian disorders and, although associated with increased risk of PD, can reflect multiple pathologies, particularly in older individuals. "Mild motor signs" appears a more appropriate term to avoid prognostic and pathological implications, and larger future studies to prospectively examine outcomes and associations of specific MPS subcategories are required. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

We here posit that measurements of midlife cognition can be instructive in understanding cognitive disorders. Even though molecular events signal possible onset of cognitive disorders decades prior to their clinical diagnoses, cognition and its possible early changes in midlife remain poorly understood. We characterize midlife cognition in a cognitively healthy population‐based sample using the Cogstate Brief Battery and test for associations with cardiovascular, adiposity‐related, lifestyle‐associated, and psychosocial variables. Learning and working memory showed significant variability and vulnerability to psychosocial influences in midlife. Furthermore, midlife aging significantly and progressively increased prevalence of suboptimal cognitive performance. Our findings suggest that physiological changes in cognition, measured with simple tests suitable for use in everyday clinical setting, may signal already in midlife the first clinical manifestations of the presymptomatic biologically defined cognitive disorders. This pilot study calls for longitudinal studies investigating midlife cognition to identify clinical correlates of biologically defined cognitive disorders. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the efficacy of a serious exergame in improving the neuropsychiatric symptoms of patients with neurocognitive disorders. Methods: X-Torp is a serious exergame combining motor and cognitive activities. Ninety-one subjects (mean age = 81.7 years, mean Mini-Mental State Examination = 18.3) were recruited in 16 centers. Centers were randomized into intervention and control centers. Subjects underwent assessment for cognitive and behavioral symptoms at baseline (BL), the end of the intervention (W12), and 12 weeks after the end of the intervention (W24). Results: The comparison of neuropsychiatric symptoms between BL and W12 and W24 showed that subjects of the intervention group improved in apathy between BL andW12. Mixed analysis (time BL,W12, W24 x group) indicated a significant increase in apathy and neuropsychiatric symptoms in the control subjects. Discussion: The use of X-Torp improved neuropsychiatric symptoms, particularly apathy. Future studies should more consistently use behavioral and neuropsychiatric symptoms as outcome measures. [ABSTRACT FROM AUTHOR]

We examined whether symptoms of dementia are improved by olfactory nerve stimulation in Alzheimer type dementia patients. First, a stick‐type olfactory identification ability test was performed in patients with Alzheimer type dementia, to select patients without olfactory dysfunctions. Then, these patients were randomly assigned into the intervention (n = 19) and the control groups (n = 17). To evaluate the effects of olfactory nerve stimulation, we exposed the intervention group to a disinfecting ethanol with added aroma extracts from ceder and the control group to the ethanol without the added aroma extracts. Each group underwent the intervention for 8 weeks, cognitive and behavioral functions were evaluated before and after treatments using the Neuropsychiatric Inventory (NPI), the Japanese version of Zarit Caregiver Burden interview (J‐ZBI), and the Alzheimer's Disease Assessment Scale‐cognitive subscale (ADAS‐cog). A significant improvement was observed in the NPI score and J‐ZBI in the intervention group compared to the control group at 4 and 8 weeks. On the other hand, there was no significant difference in the score of ADAS‐cog. Exposure to cedar fragrance improved behavioral and psychological symptoms of dementia (BPSD) in Alzheimer type dementia and may reduce the burden of nursing care. In addition to its effectiveness, the procedure is simple and minimally invasive and would be a valuable non‐pharmaceutical treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Neuropsychiatric symptoms are common in dementia. Limited data are available concerning their association with dementia in developing countries. Our aim was to describe the severity of neuropsychiatric symptoms among older people, evaluate the distress experienced by caregivers, and assess which neuropsychiatric symptoms were specifically associated with dementia among older adults in Central Africa. DESIGN: This study is part of the EPIDEMCA program, a cross‐sectional multicenter population‐based study. SETTING: The EPIDEMCA program was conducted from November 2011 to December 2012 in urban and rural areas of the Central African Republic and the Republic of the Congo. PARTICIPANTS: Participants were older people (≥65 y) included in the EPIDEMCA program who underwent a neuropsychiatric evaluation. The sample included overall 532 participants, of whom 130 participants had dementia. MEASUREMENTS: Neuropsychiatric symptoms were assessed with the brief version of the Neuropsychiatric Inventory including the evaluation of severity and associated distress. Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision, criteria were followed to diagnose dementia. A logistic regression model was used to identify associated neuropsychiatric symptoms. RESULTS: The prevalence of neuropsychiatric symptoms was 89.9% (95% confidence interval = 84.6‐95.1) among people living with dementia. The overall median severity score for neuropsychiatric symptoms was 9 [interquartile range [IQR] = 6‐12], and the overall median distress score was 7 [IQR = 4‐10]. Overall median scores of both severity and distress were significantly increased with the number of neuropsychiatric symptoms, the presence of dementia, and dementia severity. Depression, delusions, apathy, disinhibition, and aberrant motor behavior were associated with dementia after multivariate analysis. CONCLUSION: This report is one of the few population‐based studies on neuropsychiatric symptoms among older people with dementia in Sub‐Saharan Africa and the first one evaluating the severity of those symptoms and distress experienced by caregivers. Individual neuropsychiatric symptoms were strongly associated with dementia in older people and require great attention considering their burden on populations. J Am Geriatr Soc 68:180–185, 2019 [ABSTRACT FROM AUTHOR]

Hundreds of millions of COVID cases have been reported so far and long‐term lingering clinical symptoms are frequent and are called long COVID. Neurological signs including cognitive complaints are often described in long Covid. In COVID patients, the Sars‐Cov‐2 virus can reach the brain and could be responsible for cerebral anomalies observed in long COVID. Long‐term careful clinical follow‐up of these patients is necessary to detect early signs of neurodegeneration. [ABSTRACT FROM AUTHOR]

The pulvinar is primarily referred to for its role in visual processing. However, the 'visual pulvinar' only encompasses the inferior and lateral regions of this complex thalamic nucleus. The remaining medial portion (medial pulvinar, PM) establishes distinct cortical connectivity and has been associated with directed attention, executive functions and working memory. These functions are particularly impaired in neurodevelopmental disorders, including schizophrenia and attention deficit and hyperactivity disorder (ADHD), both of which have been associated with abnormal PM architecture and connectivity. With these disorders becoming more prevalent in modern societies, we review the literature to better understand how the PM can participate in the pathophysiology of cognitive disorders and how a better understanding of the development and function of this thalamic nucleus, which is most likely exclusive to the primate brain, can advance clinical research and treatments. [ABSTRACT FROM AUTHOR]

Background: The aim is to describe the association of functional capacity and cognitive functioning with 1‐year mortality in older patients with cancer in the head and neck region. Methods: We performed a cohort study in which all patients aged 70 years and older received a geriatric screening before treatment. Main outcome was 1‐year mortality. Results: A total of 102 patients were included. Median age was 78.7 years (interquartile range [IQR], 72.3‐84.5), 25% were cognitive impaired, 40% were malnourished, and 28.4% used a walking device. Overall, 1‐year mortality was 42.3%. Male sex (hazard ratio [HR], 4.30; 95% confidence interval [CI], 1.35‐13.67), malnutrition (HR, 2.55; 95% CI, 1.19‐5.16), and using a walking device (HR, 2.80; 95% CI 1.13‐6.93) were associated with higher mortality risk, independent of stage and comorbidities. Conclusion: In older patients with head and neck cancer, the mortality rates are high. Nutritional status and mobility are determinants of 1‐year mortality, independent of tumor stage, age, and comorbidity. [ABSTRACT FROM AUTHOR]

Background and Objectives: Identification of modifiable factors for mild cognitive impairment (MCI) is important since individuals with MCI are at a high risk of dementia and disability. Previous studies have suggested a potential association between periodontitis and cognitive impairment, but the results remain inconclusive. We designed a 5‐year longitudinal study to explore the association between MCI and periodontitis and periodontal inflammation in older adults. Methods: This study included 179 community‐dwelling dentate individuals (62 men and 117 women, average age: 80.1 years). A full‐mouth periodontal examination at six sites per tooth was performed at baseline. Case definitions provided by the European Workshop in Periodontology Group C (EWP definition) and the Centers for Disease Control/American Academy of Periodontology (CDC/AAP definition) were used to define severe periodontitis. Additionally, the periodontal inflamed surface area (PISA), reflecting the amount of inflamed periodontal tissue, was calculated using clinical periodontal parameters. Follow‐up cognitive examinations for MCI diagnosis were performed by neurologists 1, 2, 3, and 5 years after baseline. Odds ratios (ORs) for MCI according to the presence of periodontitis and periodontal inflammation at baseline were calculated using multilevel mixed‐effects logistic regression. Results: At baseline, 56.4% and 27.4% of the participants had severe periodontitis by the EWP and CDC/AAP definitions, respectively. After adjusting for follow‐up period and other baseline health characteristics (age, sex, smoking status, educational level, physical activity level, obesity, depression, and diabetes), severe periodontitis by either definition was significantly associated with MCI (for the EWP definition: adjusted OR = 3.58, 95% confidence interval [CI] = 1.45‐8.87; for the CDC/AAP definition: adjusted OR = 2.61, 95% CI = 1.08‐6.28). Periodontal inflammation assessed by PISA was also significantly associated with a higher OR for MCI (adjusted OR = 1.05, 95% CI = 1.01‐1.10, per 10‐mm2 increase in PISA). Conclusion: Severe periodontitis and periodontal inflammation were associated with incident MCI among older community‐dwelling men and women. [ABSTRACT FROM AUTHOR]

Falls in hospital are common and up to 70% result in injury, leading to increased length of stay and accounting for 10% of patient safety-related deaths. Yet, high-quality evidence guiding best practice is lacking. Fall prevention strategies have worked in some trials but not in others. Differences in study setting (acute, subacute, rehabilitation) and sampling of patients (cognitively intact or impaired) may explain the difference in results. This article discusses these important issues and describes the strategies to prevent falls in the acute hospital setting we have studied, which engage the cognitively impaired who are more likely to fall. We have used video clips rather than verbal instruction to educate patients, and are optimistic that this approach may work. We have also explored the option of co-locating high fall risk patients in a close observation room for supervision, with promising results. Further studies, using larger sample sizes are required to confirm our findings. [ABSTRACT FROM AUTHOR]

Objectives: To examine the effect of the Medicare Annual Wellness Visit (AWV) on the detection of cognitive impairment and on follow‐up cognitive care for older adults. Design: Retrospective matched‐cohort study. Setting: United States. Participants: A 5% random sample of fee‐for‐service Medicare beneficiaries continuously enrolled for 12 months before and after an index ambulatory visit occurring from 2011 to 2013 with no claims evidence of cognitive impairment before index. Measurements: Outcomes include 12‐month post‐index visit claims‐based measurements of cognitive impairment, including new Alzheimer's disease and related dementia (ADRD) diagnoses; medications for ADRD; and cognitive care‐related diagnostic examination such as neurobehavioral testing, brain imaging, and blood tests for thyroid‐stimulating hormone (TSH), serum B12, folate, and syphilis. We also measured changes in burden of anticholinergic medication. Results: There were no clinically relevant differences between the AWV and control groups in the rates of incident ADRD diagnoses (6.16% vs 6.86%, p<.001) and initiation of ADRD medications (1.00% vs 1.08%, p=.15), although there were differences favoring the AWV group in rates of TSH (39.80% vs 28.36%, p<.001), B12 (9.41% vs 6.97%, p<.001), folate (4.76% vs 3.72%, p<.001), and neurobehavioral (0.75% vs 0.55%, p<.001) testing. Conclusions: Although the AWV is correlated with an increase in some measures of cognitive care, such as laboratory testing for reversible causes of cognitive impairment, it does not appear to substantially increase recognition of undetected ADRD. [ABSTRACT FROM AUTHOR]

Background and purpose Motoric cognitive risk ( MCR) syndrome is a pre-dementia syndrome. There is little information on the cognitive profile of individuals with MCR syndrome and its overlap with mild cognitive impairment ( MCI) syndrome. This study aimed to examine and compare the cognitive performance of non-demented older community dwellers with and without MCR and MCI syndromes. Methods A total of 291 non-demented individuals were selected from the Gait and Alzheimer Interactions Tracking study, which is a cross-sectional study. All participants were referred to a memory clinic. Individuals with and without MCR were separated into those with and without MCI. Cognitive performance was measured using the scores of the Mini Mental Status Examination, Frontal Assessment Battery, Free and Cued Selective Reminding Test, Trail Making Test part A and B, and Stroop test. Results The prevalence of MCI was 40.1% and that of MCR was 18.2%, with a higher prevalence of MCI in MCR group compared with the non- MCR group (47.2% vs. 39.5%). Individuals with MCR and MCI syndromes had poorer cognitive performance in all domains compared with those without MCR ( P < 0.005), except for the ratio part III: part I of the Stroop test ( P = 0.345). The association between cognitive performance and MCR syndrome was worse on the Mini Mental Status Examination score [effect size, −0.57 (95% confidence interval, −1.02 to −0.12)] and Trail Making Test part B [effect size, 0.59 (95% confidence interval, 0.14-1.04)] in individuals with MCR and MCI syndromes. Conclusions Motoric cognitive risk syndrome is associated with low global cognitive performance. Association of MCR and MCI syndromes is characterized by a worse cognitive performance. [ABSTRACT FROM AUTHOR]

Aim The purpose of the present study was to explore the association between cognitive function and fear of falling in frail/non-frail older adults in a community setting. Methods We recruited 483 community-dwelling older adults aged 65 years and older (mean age 73.3 ± 5.1 years, 68.3% women). Fear of falling was assessed using a yes/no question, 'Are you afraid of falling?' Cognitive function was measured using the Mini- Mental State Examination. The five subscores of the examination were also recorded. We used the frailty criteria developed by the Cardiovascular Health Study, and divided the participants into non-frail and frail groups according to the number of affected domains. The statistical analyses were carried out separately for these two groups. Results A multiple logistic regression analysis showed that, in frail older adults, cognitive impairment was significantly associated with the absence of fear of falling ( OR 0.04, 95% CI 0.00-0.50, P = 0.012). In addition, a stepwise multivariate logistic regression analysis showed that the score on the attention and calculation subsection of the Mini- Mental State Examination was positively associated with the presence of fear of falling in frail older adults ( OR 1.83, 95% CI 1.08-3.12, P = 0.026). In contrast, cognitive impairment was not associated with fear of falling in non-frail older adults. Conclusions The results suggest that cognitive impairment, especially that in executive function, is associated with the absence of fear of falling in community-dwelling frail older adults. Geriatr Gerontol Int 2017; 17: 232-238. [ABSTRACT FROM AUTHOR]

Objectives To determine the prevalence of dementia and cognitive impairment in older people across generations. Design Two prospective cohort studies (Personnes Agées QUID ( PAQUID), Aging Multidisciplinary Investigation ( AMI)). Setting Baseline data from two subsamples of older farmers in southwestern France. Participants PAQUID (n = 595) and AMI (n = 906) participants aged 65 and older living at home at baseline (1988 PAQUID, 2008 AMI). Measurements Two methods were used to diagnose dementia: a clinical consensus diagnosis and a computer-assisted taxonomy approach (cognitive impairment with disability ( CIWD)) using Mini-Mental State Examination and instrumental activity of daily living scores. Crude and standardized prevalences (using PAQUID age-sex structure) and 95% confidence intervals were calculated, and logistic regression was used to explore confounding. Results The prevalence of consensus diagnosis of dementia was higher in AMI in 2008 than in PAQUID in 1988 (12.0% vs 5.7%, P < .001), whereas the reverse was observed for CIWD (14.8% vs 23.8%, P < .001), confirmed by logistic regressions (odds ratio ( OR) AMIvs PAQUID = 2.50, 95% confidence interval ( CI) = 1.52-4.12; ORAMIvs. PAQUID = 0.60, 95% CI = 0.42-0.87, respectively). Educational level increased and management of vascular risk factors improved over the study period, and health and living conditions improved globally. Conclusion These findings suggest global cognitive and functional improvement in old farmers (the prevalence of CIWD decreased by 40% over 20 years) and simultaneously a marked change in the subjective boundary between dementia and nondementia according to clinicians. [ABSTRACT FROM AUTHOR]

Objectives To determine whether 30-day readmissions were associated with presence of cognitive impairment more in elderly adults with heart failure ( HF) than in those with other diagnoses and whether medical teams recognized cognitive impairment. Design One-year prospective cohort quality improvement program of cognitive screening and retrospective chart review of documentation and outcomes. Setting Academic tertiary care hospital medical unit with a cardiovascular focus and an enhanced discharge program of individualized patient education. Participants Individuals aged 70 and older screened before home discharge (241 admission encounters; 121 with HF as a primary diagnosis, 120 without). The HF cohort included individuals with preserved and reduced ejection fraction. Individuals who had undergone transplantation, ventricular assist device implantation, or hemodialysis or who had a primary oncology diagnosis or hospice referral were excluded. Measurements Mini-Cog administered 48 hours or less before discharge, 30-day all-cause readmission rates, documentation of dementia or cognitive impairment, and caregiver education. Results Mini-Cog scores were less than 4 (indicating cognitive impairment) in 157 encounters (82 (67.7%) with HF, 75 (62.5%) without). Mini-Cog scores were similar in rate and distribution between groups. Individuals with HF and cognitive impairment had a significantly higher 30-day readmission rate than did the other groups (26.8% vs 13.2%; P = .01; HF, no cognitive impairment, 12.8%; no HF, no cognitive impairment, 13.3%; cognitive impairment, no HF, 13.3%). In individuals with HF and cognitive impairment, those with documented caregiver education had lower readmission rates than those without (14.3% vs 36.2%; P = .03). Fewer than 9% had documentation of cognitive impairment in the medical record. Conclusion Cognitive impairment, which is frequently undocumented, may indicate greater risk of readmission for individuals with HF than those without. Screening for cognitive impairment, adapting discharge for it, and involving family and caregivers in discharge education may help reduce readmissions. [ABSTRACT FROM AUTHOR]

Background and Objective Epidemiologic data examining the longitudinal relationship between periodontitis and cognitive status are very limited, especially in Asian populations. The present study examined the longitudinal relationship of periodontitis with cognitive decline in 85 Japanese community-dwelling individuals (average age: 79.3 years) for whom data were available from comprehensive health examinations conducted in 2010 and 2013. Material and Methods Based on a baseline full-mouth periodontal examination, severe periodontitis was defined using a Centers for Disease Control and Prevention/American Academy of Periodontology definition. Cognitive decline during the 3-year study period was defined using the results of the Mini-Mental State Examination ( MMSE). Information on age, gender, education, depression, body mass index, smoking status, alcohol use, exercise, hypertension, diabetes, history of cardiovascular disease and stroke, and baseline MMSE scores were obtained and tested as potential confounders in the statistical models. Results Among 85 study participants, 21 (24.7%) were defined as having severe periodontitis. Multivariable Poisson regression analyses revealed that severe periodontitis was significantly associated with an increased risk of cognitive decline [adjusted relative risk = 2.2; 95% confidence interval (95% CI): 1.1-4.5]. Furthermore, multivariable linear regression analyses revealed that participants with severe periodontitis had a 1.8-point greater decrease (95% CI: −3.3 to −0.2) in MMSE score than those without severe periodontitis. Conclusion Within the limitations related to its small sample size, the findings of the present study suggest that severe periodontitis is significantly associated with future decline in cognitive function among community-dwelling older Japanese subjects. [ABSTRACT FROM AUTHOR]

Objective There is paucity of information on major neurocognitive disorders in sub-Saharan Africa where the number of individuals with neurocognitive disorders is expected to increase due to demographic transition. This study aims to report on the prevalence estimates of dementia and MCI (mild cognitive impairment) in a rural community in southwest Nigeria. Materials and Methods This was a two-stage cross-sectional study of persons aged 65 years and above resident in Lalupon community, Oyo State. The Identification and IDEA (Intervention for Dementia in Elderly Africans) Study Questionnaire was used for initial screening by trained community health care workers, utilized followed by cognitive assessment using the validated IDEA cognitive screen. Functional and cognitive assessment of selected individuals was carried out during the second stage. Information obtained was used for consensus diagnosis and participants were categorized into normal, MCI and dementia using standard criteria. Results Six hundred and thirteen participants completed the study with 111 (18.1%) diagnosed as MCI while 17 (2.8%) had dementia. The age-adjusted prevalence estimates were 18.4% (95% CI: 14.9-21.9%) and 2.9% (95% CI 1.6-4.4%) for MCI and dementia, respectively. Probable Alzheimer's disease and amnestic MCI predominated. Individuals with dementia were older than both MCI and normal cases while those with MCI had significantly fewer years of schooling than the other diagnostic categories. Conclusion Almost one out of five older persons in Lalupon community had major neurocognitive impairment with MCI being six-times more common than dementia. Alzheimer's disease was the most common dementia sub-type. [ABSTRACT FROM AUTHOR]

Background: Specific comorbidities affect older patients with dementia admitted to general hospitals and may complicate the recognition of dementia. The aim of the present study was to estimate the prevalence of dementia among elderly inpatients admitted to hospital medical wards and to identify its distribution across clinical and sociodemographic conditions. Methods: From June 2011 to May 2012, a sample of elderly inpatients (≥60 years old) were screened for dementia with the Mini‐Mental State Examination and the Bayer Activities of Daily Living Scale to identify cognitive and functional impairment (CFI). Subjects with CFI underwent a diagnostic procedure for dementia using the Cambridge Mental Disorders of the Elderly Examination and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The elderly inpatients also completed a standard questionnaire to investigate sociodemographic and clinical variables and a screening procedure for depression and delirium. The data obtained were submitted to univariate and multivariate analyses. Results: The sample of 224 subjects had a mean age of 71.5 years and was mostly men (62.2%), poorly educated (≤4 years of schooling: 74.6%), and married (53.4%). CFI was observed in 84 subjects (prevalence: 37.4%; 95% confidence interval: 31.1–43.7), and dementia was observed in 31 subjects (prevalence: 17.2%; 95% confidence interval: 12.3–22.1). Dementia was related to older age and the presence of delirium, stroke, and pneumonia. Conclusions: The prevalence of CFI and dementia was high among the elderly inpatients examined. The identification of medical and sociodemographic conditions associated with a dementia diagnosis in a general hospital may be useful in the development of preventative actions. [ABSTRACT FROM AUTHOR]

Background and purpose Dementia is a leading cause of dependence amongst the aged population. Early identification of cognitive impairment could help to delay advanced stages of dependence. This study aimed at assessing the performance of three neuropsychological tests to detect cognitive disorders in elderly subjects with memory complaints. Methods The EVATEM study is a prospective multicentre cohort with a 1-year follow-up. Subjects with memory complaints were selected during preventive health examinations, and three neuropsychological tests (five-word, cognitive disorders examination, verbal fluency) were administered. Two groups were identified in memory clinics: (i) cognitively healthy individuals ( CHI) and (ii) mild cognitive impairment or demented individuals ( MCI- DI). Cross-sectional analyses were performed on data at inclusion. The relationship between the diagnosis of MCI- DI/ CHI and the neuropsychological tests was assessed using logistic regressions. The performance of the neuropsychological tests, individually and combined, to detect cognitive disorders was calculated. Results Of 585 subjects, 31.11% had cognitive disorders ( MCI, 176 subjects; DI, six subjects). Amongst the three tests studied, the odds ratio for MCI- DI was higher for the five-word test <10 [odds ratio 3.2 (1.81; 5.63)]. The best performance was observed when the three tests were combined: specificity 90.5% and sensitivity 42.4% compared to respectively 89.2% and 28.3% for the five-word test. Conclusions Despite the poor sensitivity of the five-word test, it seems to be the most adapted for the diagnosis of MCI- DI in older adults with a memory complaint, in prevention centres, taking into account its high specificity and its rapid administration compared to the other tests. [ABSTRACT FROM AUTHOR]

Introduction Lumbar puncture (LP) is increasingly performed in memory clinics. We investigated patient-acceptance of LP, incidence of and risk factors for post-LP complications in memory clinic populations. Methods We prospectively enrolled 3868 patients (50% women, age 66 ± 11 years, mini mental state examination 25 ± 5) at 23 memory clinics. We used logistic regression analysis using generalized estimated equations to investigate risk factors for post-LP complications, such as typical postlumbar puncture headache (PLPH) and back pain. Results A total of 1065 patients (31%) reported post-LP complaints; 589 patients (17%) reported back pain, 649 (19%) headache, of which 296 (9%) reported typical PLPH. Only few patients needed medical intervention: 11 (0.3%) received a blood patch, 23 (0.7%) were hospitalized. The most important risk factor for PLPH was medical history of headache. An atraumatic needle and age >65 years were preventive. Gender, rest after LP, or volume of cerebrospinal fluid had no effect. Discussions The overall risk of complications is relatively low. If risk factors shown in this study are taken into account, LPs can be safely performed in memory clinics. [ABSTRACT FROM AUTHOR]

Background and purpose: Active engagement in intellectually enriching activities (e.g. reading, hobbies) builds 'reserve' against memory decline in elders and persons with multiple sclerosis (MS), but the neural basis for this protective influence of enrichment is unknown. Herein the neuroanatomical basis of reserve against memory decline in MS patients is investigated. Methods: Relapse-onset MS patients (N = 187) underwent 3.0 T magnetic resonance imaging of the brain to quantify T2 lesion volume (T2LV) and normalized volumes of total brain, total white, total grey (using SIENAX) and thalamus, caudate, putamen, pallidum, amygdala and hippocampus (using FIRST). Patients completed a survey quantifying their engagement in early life intellectual enrichment (i.e. reading, hobbies). Verbal and visuospatial episodic memory was assessed with neuropsychological tasks in a representative subsample (N = 97). Results: Controlling for demographics and T2LV, intellectual enrichment was specifically linked to larger normalized hippocampal volume (rp = 0.213, P = 0.004), with no link to other brain volumes/structures. Moreover, greater intellectual enrichment moderated/attenuated the negative relationship between normalized total brain volume (i.e. overall cerebral atrophy) and normalized hippocampal volume (i.e. hippocampal atrophy; P = 0.001) whereby patients who engaged in more early life intellectual enrichment better maintained hippocampal volume in the face of worse overall cerebral atrophy. Finally, the link between greater intellectual enrichment and better memory was partially mediated through larger hippocampal volume. Conclusions: These findings support larger hippocampal volume as one key component of the neuroanatomical basis of reserve against memory decline in MS. These findings are consistent with previous literature on experiencedependent neuroplasticity within the hippocampus. [ABSTRACT FROM AUTHOR]

The small GTPase Rac1 is well known for regulating actin cytoskeleton reorganization in cells. Formation of extensions at the surface of the cell is required for migration and even for cell invasion and metastases. Because an elevated level and hyperactivation of this protein has been associated with metastasis in cancer, direct regulators of Rac1 are currently envisioned as a potential strategy to treat certain cancers. Less research, however, has been done regarding the role of this small GTP-binding protein in brain development, where it has an important role in dendritic spine morphogenesis through the regulation of actin. Alteration of dendritic development and spinogenesis has been often associated with mental disorders. Rac1 is associated with and required for learning and the formation of memories in the brain. Rac1 appears to be dysregulated in certain neurodevelopmental disorders that present all these three alterations: mental retardation, atypical synaptic plasticity and aberrant spine morphology. Thus, to develop novel therapies for rescuing cognitive impairment, a reasonable approach might be to target this protein, Rac1, which plays a pivotal role in directing signals that regulate actin dynamics, which in turn might have an effect in spine cytoarchitecture and synaptic function. It is possible that novel drugs that regulate Rac1 activation and function could modulate actin cytoskeleton and spine dynamics, representing potential candidates to repair intellectual disability in disorders associated with spine abnormalities. Herein, we present a list of the current Rac1 inhibitors that might fulfill this role together with a summary of the latest findings concerning their function as they relate to neuronal studies. [ABSTRACT FROM AUTHOR]

Combination antiretroviral therapy transformed human immunodefiency virus (HIV)-infection from a terminal illness to a manageable condition, but these patients remain at a significantly elevated risk of developing cognitive impairments and the mechanisms are not understood. Some previous neuroimaging studies have found hyperactivation in frontoparietal networks of HIV-infected patients, whereas others reported aberrations restricted to sensory cortices. In this study, we utilize high-resolution structural and neurophysiological imaging to determine whether alterations in brain structure, function, or both contribute to HIV-related cognitive impairments. HIV-infected adults and individually matched controls completed 3-Tesla structural magnetic resonance imaging (sMRI) and a mechanoreception task during magnetoencephalography (MEG). MEG data were examined using advanced beamforming methods, and sMRI data were analyzed using the latest voxel-based morphometry methods with DARTEL. We found significantly reduced theta responses in the postcentral gyrus and increased alpha activity in the prefrontal cortices of HIV-infected patients compared with controls. Patients also had reduced gray matter volume in the postcentral gyrus, parahippocampal gyrus, and other regions. Importantly, reduced gray matter volume in the left postcentral gyrus was spatially coincident with abnormal MEG responses in HIV-infected patients. Finally, left prefrontal and postcentral gyrus activity was correlated with neuropsychological performance and, when used in conjunction, these two MEG findings had a sensitivity and specificity of over 87.5% for HIV-associated cognitive impairment. This study is the first to demonstrate abnormally increased activity in association cortices with simultaneously decreased activity in sensory areas. These MEG findings had excellent sensitivity and specificity for HIV-associated cognitive impairment, and may hold promise as a potential disease marker. Hum Brain Mapp 36:897-910, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

There is a growing body of evidence pointing to the pivotal role of alpha-7 nicotinic acetylcholine receptor ( α7 nAchR) dysfunction in cognitive disorders such as Alzheimer's disease or schizophrenia. This study was undertaken to establish and characterize an in vivo model for cognitive disorder secondary to the blockade of α7 nAChR by its specific antagonist, methyllycaconitine (MLA). The results show that MLA elicited cognitive dysfunction as assessed by reduced spontaneous alternation of mice in the T-maze. The maximal effect of MLA produced 25-30% reduction in the spontaneous alternation of mice, a level comparable with that induced by the muscarinic antagonism of scopolamine. Donepezil and galantamine fully reversed both MLA and scopolamine-induced cognitive dysfunction. However, the ED50 of donepezil and galantamine was significantly shifted to the left in the MLA- compared to scopolamine-treated mice (0.0005 and 0.002 mg/kg for donepezil; 0.0003 and 0.7 mg/kg for galantamine). Moreover, memantine elicited marked reversion of cognitive dysfunction (up to 70%) in MLA-treated mice while only a weak reversal effect at high dose of memantine (less than 20%) was observed in scopolamine-treated mice. The above findings indicate that MLA-induced cognitive dysfunction in the mouse is highly sensitive and more responsive to the current procognitive drugs than the traditional scopolamine-based assay. Thus, it can be of value for the preclinical screening and profiling of cognition-enhancing drugs. [ABSTRACT FROM AUTHOR]

In recent years it has been firmly established that apart from the classic renin-angiotensin system ( RAS) comprising angiotensin ( Ang) II, angiotensin converting enzyme ( ACE; responsible for Ang II generation) and the angiotensin AT1 receptor ( AT1R), there also exist protective arms of the RAS that comprise the angiotensin AT2 receptor ( AT2R), Ang-(1-7), ACE2 (mainly responsible for Ang-(1-7) synthesis) and Mas, the receptor for Ang-(1-7)., Stimulation of AT2 R promotes neuronal differentiation, neurite outgrowth and axonal regeneration, which results in an acceleration of repair and improved functional outcome after injury of peripheral nerves or the spinal cord., Stimulation of AT2 R and the receptor Mas has been shown to reduce infarct size and ameliorate neurological deficits in various animal models of stroke. The underlying mechanisms of action are comprised of activation of direct neurotrophic, anti-inflammatory and anti-oxidant pathways, as well as the augmentation of cerebral blood flow., Cognitive function is improved by AT2 R stimulation due, at least in part, to increased cerebral blood flow. There is indirect evidence that Ang-(1-7) could also play a role in protection against cognitive decline, but studies confirming this have not yet been published., In view of the data reviewed in this article, it can be assumed that the protective arms of the RAS are putative targets in the treatment of neurological diseases, which involve tissue damage or cognitive impairment. [ABSTRACT FROM AUTHOR]

Objective To examine the relationship of neuropsychiatric symptoms and apolipoprotein E (APOE) ε4 allele status to dementia at baseline and progression to dementia in older adults with and without cognitive impairment, no dementia (CIND). Methods Adults ( n = 856) 71 years and older (mean age = 79.15 years), 12.8% ethnic minority and 60.6% women, completed neuropsychological tests and APOE genotyping, and a proxy informant completed the Neuropsychiatric Inventory. Results After adjusting for age and education, neuropsychiatric symptoms and APOE ε4 were independently associated with CIND and dementia status at baseline (compared with cognitively normal). Further, neuropsychiatric symptoms predicted progression to dementia at 16- to 18-month follow-up among participants with CIND at baseline; the presence of these symptoms decreased the risk of progression from normal to CIND or dementia at 36 to 48 months. Conclusion Findings provide cross-sectional and longitudinal support for the role of neuropsychiatric symptoms in the prediction of cognitive impairment, particularly dementia. APOE ε4, although important, may be a less robust predictor. This investigation highlights the importance of behavioral symptoms, such as neuropsychiatric symptom status or frequency/severity, as predictors of future cognitive decline. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Freezing of gait (FOG) is part of a complex clinical picture in Parkinson's disease (PD) and is largely refractory to standard care. Diverging hypotheses exist about its origins, but a consolidated view on what determines FOG is lacking. The aim of this study was to develop an integrative model of FOG in people with PD. This cross-sectional study included 51 Parkinson subjects: 24 patients without FOG and 27 with FOG matched for age, gender, and disease severity. Subjects underwent an extensive clinical test battery evaluating general disease characteristics, gait and balance, nongait freezing, and cognitive functions. The relative contribution of these outcomes to FOG was determined using logistic regression analysis. The combination of the following four independent contributors provided the best explanatory model of FOG (R2 = 0.49): nongait freezing; levodopa equivalent dose (LED); cognitive impairment; and falls and balance problems. The model yields a high-risk profile for FOG ( P > 95%) when Parkinson patients are affected by at least one type of nongait freezing (e.g., freezing of other repetitive movements), falls or balance problems during the last 3 months, and a Scales for Outcomes in Parkinson's Disease-Cognition score below 28. A high LED further increases the risk of FOG to 99%. Nongait freezing, increased dopaminergic drug dose, cognitive deficits, and falls and balance problems are independent determinants of FOG in people with PD and may play a synergistic role in its manifestation. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Cognitive disorders appearing in the course of bipolar disease have been identified, and recent studies have defined the neuropsychological characteristics of this pathology, which includes attention, executive function, memory and language disorders. However, questions remain concerning the appearance of dementia symptoms over the course of bipolar disorder in certain patients: is it a chance association or is there a connection between bipolar disorders and dementia? If the latter hypothesis is considered, what is the nature of the dementia, which might be considered as a dementia specific to bipolar disorder? Current clinical, neuropsychological and cerebral imaging data are inconclusive, but similarities with frontotemporal dementia might be highlighted. Functional imaging studies might provide answers as well as more specific tests in neuropsychology. The cause of cognitive damage in bipolar disease also raises questions concerning a neurodevelopmental or neurodegenerative process, because several factors seem to influence cognition and these two processes might occur simultaneously. Long-term studies are necessary to determine whether cognitive deterioration in bipolar disease is stable or progressive. There might also be different neurobiological subgroups of patients with bipolar disease. [ABSTRACT FROM AUTHOR]

Semantic dementia (SD) has been recognized as a representative of dementia with presenile onset; however, recent epidemiological studies have shown that SD also occurs in the elderly. There have been few studies about the differences of clinical profiles between early-onset SD (EO-SD) and late-onset SD (LO-SD). Age-associated changes in the brain might cause some additional cognitive and behavioural profiles of LO-SD in contrast to the typical EO-SD cases. The aim of the present study was to clarify the characteristics of neuropsychological, and behavioural and psychological symptoms of dementia (BPSD) profiles of LO-SD patients observed in screening tests in comparison with EO-SD patients and late-onset Alzheimer's disease (LO-AD) patients as controls. Study participants were LO-SD ( n = 10), EO-SD ( n = 15) and LO-AD ( n = 47). We examined the Mini-Mental State Examination (MMSE), the Raven's Coloured Progressive Matrices (RCPM), the Short-Memory Questionnaire (SMQ), the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI). Both SD groups scored significantly lower than the LO-AD patients in 'naming' of the MMSE. In the 'construction' score of the MMSE and the RCPM score, however, the LO-SD patients as well as the LO-AD patients were significantly lower than the EO-SD patients. In the SMQ score, 'euphoria' and 'disinhibition' scores of the NPI, the SRI total and subscale scores, both SD groups were significantly higher, whereas in the 'delusion' score of the NPI, both SD groups were significantly lower than the LO-AD patients. Visuospatial and constructive skills of LO-SD patients might be mildly deteriorated compared with EO-SD patients, whereas other cognitive and behavioural profiles of LO-SD are similar to EO-SD. Age-associated changes in the brain should be considered when we diagnose SD in elderly patients. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine how often neuroimaging confirms, clarifies, or contradicts initial diagnoses of late-life cognitive disorders. DESIGN: Retrospective case review. SETTING: Outpatient clinic specializing in memory disorders. PARTICIPANTS: One hundred ninety-three consecutively referred cognitively impaired patients. MEASUREMENTS: Diagnoses using research criteria were developed for each patient at the first visit and ranged from cognitive impairment without dementia to dementias of single, complex, or indeterminate etiology. Structural (noncontrast magnetic resonance imaging) and perfusion (technetium-99m ethyl cysteine dimer single photon emission computed tomography) images were categorized together as normal, suggestive of specific diseases, or abnormal/not diagnostic. RESULTS: When a single neurodegenerative disease was suspected clinically (n=94), imaging confirmed the diagnosis in 50, contradicted the diagnosis in 32, and was abnormal/not diagnostic in 12. When more than one neurodegenerative etiology was clinically suspected (n=21), imaging assigned a single diagnosis in 13 and only cerebrovascular disease in one and was abnormal/not diagnostic in seven. In dementia not otherwise specified (NOS) (n=33), imaging suggested a specific etiology in 23 and was abnormal/not diagnostic in 10. Abnormal/not diagnostic images were more common in cognitive disorder NOS (n=25, 68%) than in other clinical groups (22%, chi-square=22.8 P<.001). Neuroimaging indicators of cerebrovascular disease were common (60% prevalence) but not predicted by the presence of vascular risk factors alone. CONCLUSION: Overall, neuroimaging confirmed, clarified, or contradicted the initial clinical diagnosis in more than 80% of patients, whereas fewer than 20% had abnormal/not diagnostic patterns. Imaging suggested a complex dementia etiology in 21% of cases clinically thought to be caused by a single process, whereas 46% of complex clinical differential diagnoses appeared to reflect a single causal pattern. Further work is needed to determine whether refinement of clinical diagnoses using specialized neuroimaging improves clinical decision-making and patient outcomes. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop and evaluate low-cost technology for cognitive rehabilitation in older individuals with dementia and document changes stemming from a clinical case study using these tools. An activity board, a calendar, a routine organizer and a software program were used and evaluated by specialists (n = 7). A pre-post-case study with an elderly male with dementia was undertaken for four months. All rehabilitation resources were classified as appropriate by the specialists. Post-intervention scores demonstrated improvement in cognitive functioning and daily activities at home. There is a need for further research to assess the therapeutic effects in patients with dementia applying equipment and software to improve cognitive function. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: To examine the extent to which cognitive disorders influenced the feasibility and accuracy of both the 20-item and the 10-item Center for Epidemiologic Studies Depression Scale (CES-D). Methods: Cross-sectional analyses of 223 first-visit patients in a psychiatric clinic and 108 patients in a psychiatric department in a general hospital were conducted. To assess the influence of age, gender, and the presence of cognitive disorders on the feasibility of both versions of the CES-D, multiple logistic regression was performed with feasibility per se as the dummy dependent variable. In order to assess the accuracy of the CES-D, receiver operating characteristic (ROC) analysis was performed. Results: The infeasibility of both types of CES-D were so strongly associated with the presence of cognitive disorders that it can be used as an indicator of cognitive impairment. Moreover, the 10-item CES-D had almost as acceptable an internal consistency reliability as the 20-item CES-D in the study settings. Conclusions: Information obtained from both versions of the CES-D could be utilized fully, using infeasibility as an indicator of cognitive disorders, in psychiatry settings. Other screening instruments with as heavy a cognitive load as the CES-D can also be used in the same manner as an indicator of cognitive disorders to save the need for instruments specifically designed for dementia. Such usage can decrease the burden on both the respondent and the clinician in clinical practice. [ABSTRACT FROM AUTHOR]

According to Evidence-Based-Medicine, any proposal for the rationale treatment of mild cognitive impairment (MCI) must be based on the results of double-blind, randomized clinical trials (RCTs). However, since MCI at the present time does not constitute a homogeneous clinical syndrome, it is still inappropriate to propose a specific drug treatment. Moreover, RCTs assessing the therapeutic value of acetylcholinesterase-inhibitors (AChEIs) are negative either trying to improve symptoms (memory performance) or preventing the conversion from MCI to real Alzheimer's Disease (AD). The same negative results were obtained with drugs targeting some systems considered as the early steps of the pathophysiological cascade leading to dementia: non-steroidal anti-inflammatory compounds (rofecoxib), sex steroid hormones (testosterone, estrogens), or antioxidants (tocopherol). Either MCI is considered as the very early phase of development of AD (and then the treatments will aim at preventively antagonizing the hallmarks of the disease) or MCI is a new entity (and then the drugs will target the associated neurochemical disturbancies such as tau protein or soluble Aβ oligomers); MCI could also be considered as a monosymptomatic syndrome (amnesia) leading to the development of pure pro-mnestic drugs. These three hypotheses will be presented on the basis of the neurobiology and the pharmacology, and examples of potentially active candidates will be discussed. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Stroke and cognitive impairment are inter-related. The purpose of this study was to show the natural evolution of cognitive performance during the first year after a stroke, and to show which factors that predict cognitive decline. Subjects were patients with a first-ever stroke who were treated in a stroke unit. A total of 160 patients were included. At baseline patients were evaluated with regard to stroke type, stroke severity, pre-stroke dementia and other risk factors. Mini Mental State Examinations (MMSE) were performed after 1 week and after 1 year. Patients had a median increase of 1 point (range −8 to +9) on the MMSE. Thirty-two pre cent of the patients deteriorated, 13% were unchanged, and 55% improved. Lacunar infarction (LI) and left-sided stroke were associated with a failure to exhibit improvement. Patients with LI had an average decline of 1.7 points, whilst patients with other stroke types had an average increase of 1.8 points. Most stroke survivors improve cognitively during the first year after the event. The outcome for LI patients is worse, which suggests that LI may serve as a marker for concomitant processes that cause cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives To assess the utility of asking for presence of progressive forgetfulness (PF) prior to administering the Abbreviated Mental Test (AMT) when screening for dementia in the community-dwelling elderly Chinese. Methods This was a two-phased community-based survey of elderly subjects (≥50 yrs). In phase one, subjects were asked for PF and administered the AMT. Those having PF or an impaired AMT performance were evaluated clinically for dementia in phase two, which also included a randomly selected sample of 35 subjects with no PF and who passed the AMT. Results 2566 subjects completed phase one interview, of which 128 subjects completed phase two. Overall prevalence of PF, failed AMT and dementia were 2.4%, 2.2%, 0.9% respectively. The sensitivity of PF for dementia was 95.7% with specificity of 45.1%. PF was significantly associated with depression in the young-old (50–74 yrs) but not in the old-old (≥75 yrs) age group, after adjusting for dementia. The probability of subjects (%) in the four possible diagnostic combinations of PF and AMT in the young-old and (old-old) age groups were 0 (0.06) in the no PF/ passed AMT, 0 (0.44) in the no PF/failed AMT, 0.23 (9.2) in the PF/passed AMT and 3.6 (43) in the PF/failed AMT groups. Conclusion In screening for the most common dementias, AMT administration is not required if PF is absent. AMT is also of no added utility for diagnosing dementia in older subjects with PF. Younger subjects with PF should be closely evaluated for depression especially if they passed the AMT, and dementia, if they failed the AMT. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Alpha-mannosidosis is characterized by mild to moderate intellectual disability (ID), moderate to severe neurosensory hearing loss, frequent infections, psychomotor disturbances and skeletal dysmorphism. For the first time, a panel of nine alpha-mannosidosis patients with psychiatric symptoms is presented. The clinical picture has several similarities: a physical or psychological stressor precedes a rapid development of a state of confusion, delusions, hallucinations, anxiety and often depression leading to a severe loss of function. This usually lasts 3–12 weeks, and is followed by a period of somnolence and asthenia. It may be more prevalent in females. In four of the described patients search for organic causes of the syndrome was performed, but revealed only negative findings. Because of the limited number of cases no firm conclusion about the benefit of various psychotropic drugs can be drawn from our observation. Psychiatric symptoms could affect as many as 25% of patients with alpha-mannosidosis. First onset is typically in late puberty to early adolescence. The episodes may be recurrent, and of limited duration although medication may be necessary to alleviate symptoms. Our observations indicate that alpha-mannosidosis is associated with an increased risk of psychiatric symptoms. These should not be dismissed as part of the ID but should give rise to the initiation of adequate diagnostic work-up, treatment and support. [ABSTRACT FROM AUTHOR]

Ecstasy use has often been found to be associated with psychopathology, yet this research has so far been based largely on subjective symptom ratings. To investigate whether ecstasy users suffered from long-term psychopathological consequences. We compared the prevalence of Diagnostic and Statistical Manual version IV (DSM-IV) mental disorders in 30 current and 29 former ecstasy users, 29 polydrug and 30 drug-naive controls. Groups were approximately matched by age, gender and level of education. The current ecstasy users reported a life-time dose of an average of 821 and the former ecstasy users of 768 ecstasy tablets. Ecstasy users did not significantly differ from controls in the prevalence of mental disorders, except those related to substance use. Substance-induced affective, anxiety and cognitive disorders occurred more frequently among ecstasy users than polydrug controls. The life-time prevalence of ecstasy dependence amounted to 73% in the ecstasy user groups. More than half of the former ecstasy users and nearly half of the current ecstasy users met the criteria of substance-induced cognitive disorders at the time of testing. Logistic regression analyses showed the estimated life-time doses of ecstasy to be predictive of cognitive disorders, both current and life-time. The motivation for ecstasy use is not likely to be self-medication of pre-existing depressive or anxiety disorders as these did not occur more frequently in the ecstasy users than in control groups or in the general population. Cognitive disorders still present after over 5 months of ecstasy abstinence may well be functional consequences of serotonergic neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA). [ABSTRACT FROM AUTHOR]

ABSTRACT Piracetam, a derivative of the neurotransmitter γ-aminobutyric acid (GABA), has a variety of physiological effects that may result, at least in part, from the restoration of cell membrane fluidity. At a neuronal level, piracetam modulates neurotransmission in a range of transmitter systems (including cholinergic and glutamatergic), has neuroprotective and anticonvulsant properties, and improves neuroplasticity. At a vascular level, it appears to reduce erythrocyte adhesion to vascular endothelium, hinder vasospasm, and facilitate microcirculation. This diverse range of physiological effects is consistent with its use in a range of clinical indications. Its efficacy is documented in cognitive disorders and dementia, vertigo, cortical myoclonus, dyslexia, and sickle cell anemia. While high doses are sometimes necessary, piracetam is well tolerated. [ABSTRACT FROM AUTHOR]

Compound S 17092 is a potent and selective inhibitor of prolyl endopeptidase (EC 3.4.21.26, PEP) that may be of therapeutic value for the treatment of memory impairment associated with neurodegenerative diseases. In the present study, we investigated the effects of S 17092 on the catabolism of the promnesic neuropeptides thyrotrophin-releasing hormone (TRH) and arginine-vasopressin (AVP) in the rat brain.In vitro, bacterial PEP hydrolysed both TRH and AVP, and the breakdown of the two peptides was almost completely prevented by 10−5 M S 17092.In vivo, a single oral administration of S 17092 provoked a significant increase in TRH-like immunoreactivity (TRH-LI) in the cerebral cortex (+63% for a 10 mg/kg dose and +72% for a 30 mg/kg dose), as well as AVP-LI in the hippocampus (+54% for a 30 mg/kg dose), but did not affect TRH-LI in the amygdala nor AVP-LI in the cerebral cortex. Chronic administration of S 17092 (10 or 30 mg/kg daily) lead to a significant increase in THR-LI in the cerebral cortex (+55% and +56%, respectively), but did not modify AVP-LI in the hippocampus, nor in the cerebral cortex. These results show that the selective PEP inhibitor S 17092 increases TRH and AVP content in discrete regions of the rat brain. The present data suggest that the promnesic and antiamnesic effects of S 17092 can be accounted for, at least in part, by blockage of AVP and TRH degradation by PEP. [ABSTRACT FROM AUTHOR]

Objectives The Kingston Standardized Cognitive Assessment—Revised (KSCA-R) was designed to be a cognitive screening tool available to health professionals who were not trained in specialized cognitive assessment techniques. It was introduced to bridge the gap between brief, narrowly focused rating scales, and intensive, expensive, full neuropsychological assessments. We now present the Brief Kingston Standardized Cognitive Assessment—Revised (BriefKSCA-R). Methods Groups of Alzheimer's disease patients, patients suffering from other dementias, and a group of normal community dwelling elderly were assessed using the BriefKSCA-R. Results This shortened version of the full Kingston Standardized Cognitive Assessment—Revised can be given in half the time while retaining most of the full KSCA-R's effectiveness. Conclusions Suitable for a quick screening, or follow-up of patients already more fully assessed. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine dihydrochloride salt] is a selective neuronal nicotinic receptor (NNR) modulator with cognitive enhancing properties in animal models of cognitive functioning. Amongst NNR subtypes, ABT-089 shows selectivity for the cytisine binding site on the α4β2 receptor subtype as compared to the α-bungarotoxin (α-BgT) binding sites on the α7 and α1β1δγ receptor subtypes. In functional in vitro electrophysiological and cation flux assays, ABT-089 displays differential activity including agonism, partial agonism and antagonism depending upon the NNR subtype and assay. ABT-089 is as potent and efficacious as (-)-nicotine at evoking acetylcholine (ACh) release from hippocampal synaptosomes. Furthermore, ABT-089 is neuroprotective against excitotoxic glutamate insults, with even greater potency seen after chronic treatment. Similarly, ABT-089 is effective in models of cognitive functioning, including enhancement of baseline functioning as well as improvement of impaired cognitive functioning seen following septal lesioning and natural aging. In neuroprotective assays the compound is most potent by chronic administration. In stark contrast to the positive effects in the cognitive models, ABT-089 shows little propensity to induce adverse [ABSTRACT FROM AUTHOR]

The original Kingston Standardized Cognitive Assessment (KSCA) was designed to assess cognitive functioning in the elderly with suspected organic brain damage (i.e. dementia). It was specifically designed to be a relatively quickly administered assessment tool available to mental health professionals who were not trained in specialized cognitive assessment techniques. It was introduced over a decade ago to bridge a gap between brief, narrowly focused rating scales, and intensive, expensive, full neuropsychological assessments. Recently, a revision of the KSCA was completed. This revision includes the addition of a word-list memory task with immediate recall, delayed recall and recognition formats, as well as new norms for patients with Alzheimer's disease (AD). The updated norms reflect the abilities of higher-functioning (community-dwelling) patients. In order to facilitate the Revised KSCAs use we have developed a new scoring and analysis form as well as a more comprehensive scoring and administration manual. These changes have resulted in better detection of earlier Alzheimer's disease and use of comparison groups that reflect the changing referral base. The structure of the revised scale and updated normative data are described. An illustrative clinical case example is also provided. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives – The purpose of the present study was to divide visual object recognition into different stages and to reveal which of these stages are impaired in early Alzheimer's disease (AD). Methods – Performance in object detection, familiarity detection, semantic name and word categorization, and identification with naming were studied by using two-choice reaction-time tasks. Ten patients with newly diagnosed AD and 14 healthy subjects were studied. Results – Patients with early AD had impairments in several stages of the object recognition process. After controlling for the basic visuomotor slowness, they were as fast and as accurate as the controls in object detection, but had difficulties in all stages that required semantic processing. Conclusions – Semantic memory impairments contribute to the deficits in visual object recognition in early AD. Thus, the semantic memory deficit may be manifested in several ways in the difficulties that AD patients experience in everyday life. [ABSTRACT FROM AUTHOR]

Subtle neuropsychological deficits have been described in patients affected by amyotrophic lateral sclerosis (ALS) without dementia. Overall, selective impairment in memory function has been reported, but the source of memory impairment in ALS has yet to be defined. We performed neuropsychological screening in 20 ALS patients. Semantic encoding and post-encoding cue effects on the retrieval of word lists were investigated in the ALS patients and normal controls. Severity of memory impairment was correlated to cerebral blood perfusion detected by single photon emission computed tomography (SPECT). ALS patients showed moderate impairments in frontal and memory tests. Short-term memory was normal, while serial position retrieval of word lists with normal recency effect but poor primacy effect showed long-term memory deficit. ALS patients performed better in cued encoding than in cued post-encoding recall condition. In the cued post-encoding condition, the primacy effect in word list recall improved significantly in controls, but not in ALS patients, as compared with both the free recall and cued encoding conditions. SPECT hypoperfusion was observed in frontal and temporal areas in ALS patients. ALS patients showed a long-term memory deficit which did not improve in cued post-encoding condition as it does for controls. We hypothesize abnormal retrieval processes related to frontal lobe dysfunction which entails difficulties in generating stable long-memory traces at encoding. [ABSTRACT FROM AUTHOR]

Subtle neuropsychological deficits have been described in patients affected by amyotrophic lateral sclerosis (ALS) without dementia. Overall, selective impairment in memory function has been reported, but the source of memory impairment in ALS has yet to be defined. We performed neuropsychological screening in 20 ALS patients. Semantic encoding and post-encoding cue effects on the retrieval of word lists were investigated in the ALS patients and normal controls. Severity of memory impairment was correlated to cerebral blood perfusion detected by single photon emission computed tomography (SPECT). ALS patients showed moderate impairments in frontal and memory tests. Short-term memory was normal, while serial position retrieval of word lists with normal recency effect but poor primacy effect showed long-term memory deficit. ALS patients performed better in cued encoding than in cued post-encoding recall condition. In the cued post-encoding condition, the primacy effect in word list recall improved significantly in controls, but not in ALS patients, as compared with both the free recall and cued encoding conditions. SPECT hypoperfusion was observed in frontal and temporal areas in ALS patients. ALS patients showed a long-term memory deficit which did not improve in cued post-encoding condition as it does for controls. We hypothesize abnormal retrieval processes related to frontal lobe dysfunction which entails difficulties in generating stable long-memory traces at encoding. [ABSTRACT FROM AUTHOR]