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Dementia is a clinical diagnosis without curative treatment. It is uncertain whether ancillary testing is beneficial for patients. This study investigates the association between use of diagnostic tests and time to poor outcome and health care costs. Nationwide register-based cohort study using health care reimbursement data in the Netherlands. All Dutch hospitals, including 13,312 patients diagnosed with dementia in 2018. Diagnostic testing included computed tomography or magnetic resonance imaging (CT/MRI), neuropsychological examination (NPE), nuclear imaging (PET/SPECT), electroencephalography (EEG), and cerebrospinal fluid (CSF) testing. We compared time to poor outcome (institutionalization or death) and costs per month from 2018 to 2021 between those who underwent a specific diagnostic test in previous years to controls, propensity score matched for age, sex, type of hospital, and comorbidity. Time to poor outcome in those who underwent CT/MRI, EEG, or CSF testing was similar to those who did not, but was longer for those who underwent NPE. Time to poor outcome was shorter in patients who underwent PET/SPECT. Patients who underwent CSF testing or PET/SPECT had higher mean total health care costs as compared to controls (CSF €248, 95% CI 64-433; PET/SPECT: €315, 95% CI 179-451). NPE during the diagnostic trajectory was associated with lower total health care cost (–€127, 95% CI –62, –193). NPE was associated with longer time to poor outcome and lower health care costs, potentially due to confounding by indication. Patients who underwent neuroimaging (CT, MRI, SPECT/PET), CSF testing, or EEG for dementia diagnostics did not experience a longer time to poor outcome or lower health care costs. This emphasizes the importance of clinical examination as anchor for the diagnosis of dementia. [ABSTRACT FROM AUTHOR]

Keywords: Parkinson's disease; alpha-synuclein; cinpanemab; prasinezumab EN Parkinson's disease alpha-synuclein cinpanemab prasinezumab 2289 2291 3 01/06/23 20221230 NES 221230 Removing misfolded protein depositions from the brain, or preventing them from accumulating altogether, seems like a rational therapeutic approach to arrest the process of neurodegeneration in persons with diseases in which these depositions are a key pathology. Two recent phase II clinical trials in PD patients tested this hypothesis, by treating levodopa-naïve patients with early-stage PD with monoclonal antibodies - in the SPARK study, intravenously administered cinpanemab [[1]] and in the PASADENA study, intravenous prasinezumab [[2]]. Alpha-synuclein would be the quintessential protein to target in Parkinson's disease (PD). [Extracted from the article]

Background: Older people with subjective memory complaints (SMC) and Instrumental Activities of Daily Living impairments (IADL-I) have an increased risk of developing dementia. Previous reports suggest that the predictive value of SMC and IADL-I may differ between sexes, leaving possible consequences for personalized risk prediction and prognosis. However, none of these studies addressed the competing risk of death, which may substantially differ between sexes.Objective: We investigated sex-differences in the association between IADL-I, SMC, and incident dementia and mortality as competing risk.Methods: 3,409 community-dwelling older people without dementia (mean age 74.3±2.5), were followed for 6.7 years (median). Baseline SMC were assessed using the 15-item Geriatric Depression Scale memory question, and IADL-I using the Academic Medical Center Linear Disability Score. Potential sex-differences in the predictive value of SMC and IADL-I were assessed using Cox regression models with an interaction term for sex.Results: HRs for isolated SMC and SMC + IADL-I and risk of dementia were higher in women (HR: 2.02, 95% CI = 0.91-4.46, p = 0.08; HR:2.85, 95% CI = 1.65-4.91, p < 0.001) than in men (HR:1.52, 95% CI = 0.86-2.69, p = 0.18; HR:1.24, 95% CI = 0.62-2.49, p = 0.54), but these sex-differences were not significant. Conversely, HRs for isolated IADL-I and risk of mortality were higher in men (HR:1.56, 95% CI = 1.18-2.05, p = 0.002) than in women (HR:1.14, 95% CI = 0.80-1.62, p = 0.48), but again, these sex-differences were not significant.Conclusion: The predictive value of SMC and IADL-I for the risk of dementia and mortality was not significantly modified by sex. However, the competing risk of death for these factors differed considerably between men and women, suggesting it is an essential factor to consider when comparing sex-differences in IADL/dementia risk. [ABSTRACT FROM AUTHOR]

Background and purpose: The optimal management of post‐stroke cognitive impairment (PSCI) remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence‐based recommendations to assist clinicians in decision making regarding prevention, diagnosis, treatment and prognosis. Methods: Guidelines were developed according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews, assessed the quality of the available evidence, and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations. Results: There was limited randomized controlled trial (RCT) evidence regarding single or multicomponent interventions to prevent post‐stroke cognitive decline. Lifestyle interventions and treating vascular risk factors have many health benefits, but a cognitive effect is not proven. We found no evidence regarding routine cognitive screening following stroke, but recognize the importance of targeted cognitive assessment. We describe the accuracy of various cognitive screening tests, but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post‐stroke cognition. The association between PSCI and acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on brain magnetic resonance imaging may help predict cognitive outcomes. Conclusions: These guidelines highlight fundamental areas where robust evidence is lacking. Further definitive RCTs are needed, and we suggest priority areas for future research. [ABSTRACT FROM AUTHOR]

Purpose: Family physicians need simple yet comprehensive algorithms to discriminate between community-dwelling older persons who are at increased risk of dementia and those who are not. We aimed to investigate associations between incident dementia and responses to a single question regarding subjective memory complaints (SMC) combined with scores on 2 simple memory tests that are easy to use in the primary care setting.Methods: Analyses were based on data from 3,454 community-dwelling older persons who participated in the 6- to 8-year Prevention of Dementia by Intensive Vascular Care (preDIVA) trial, yielding 21,341 person-years of observation. Participants were considered a single cohort. We used Cox models to assess separate and combined associations of SMC, an imperfect score on the Mini-Mental State Examination delayed recall item (MMSE-5), and an imperfect score on the Visual Association Test (VAT) with future dementia.Results: Subjective memory complaints alone were associated with future dementia (hazard ratio [HR] = 3.01; 95% CI, 2.31-3.94; P <.001), as were the MMSE-5 (HR = 2.14; 95% CI, 1.59-2.87; P <.001) and VAT (HR = 3.19; 95% CI, 2.46-4.13; P <.001) scores. After a median follow-up of 6.7 years, the occurrence of dementia ranged from 4% to 30% among persons with SMC, depending on the MMSE-5 and VAT scores. These test scores did not substantially alter the association with future dementia for persons without SMC.Conclusions: In persons with SMC, the strength of the association between future dementia and an imperfect MMSE-5 score depends substantially on the VAT score. [ABSTRACT FROM AUTHOR]

Cardiovascular risk prediction is mainly based on traditional risk factors that have been validated in middle-aged populations. However, associations between these risk factors and cardiovascular disease (CVD) attenuate with increasing age. Therefore, for older people the authors developed and internally validated risk prediction models for fatal and non-fatal CVD, (re)evaluated the predictive value of traditional and new factors, and assessed the impact of competing risks of non-cardiovascular death. Post hoc analyses of 1811 persons aged 70-78 year and free from CVD at baseline from the preDIVA study (Prevention of Dementia by Intensive Vascular care, 2006-2015), a primary care-based trial that included persons free from dementia and conditions likely to hinder successful long-term follow-up, were performed. In 2017-2018, Cox-regression analyses were performed for a model including seven traditional risk factors only, and a model to assess incremental predictive ability of the traditional and eleven new factors. Analyses were repeated accounting for competing risk of death, using Fine-Gray models. During an average of 6.2 years of follow-up, 277 CVD events occurred. Age, sex, smoking, and type 2 diabetes mellitus were traditional predictors for CVD, whereas total cholesterol, HDL-cholesterol, and systolic blood pressure (SBP) were not. Of the eleven new factors, polypharmacy and apathy symptoms were predictors. Discrimination was moderate (concordance statistic 0.65). Accounting for competing risks resulted in slightly smaller predicted absolute risks. In conclusion, we found, SBP, HDL, and total cholesterol no longer predict CVD in older adults, whereas polypharmacy and apathy symptoms are two new relevant predictors. Building on the selected risk factors in this study may improve CVD prediction in older adults and facilitate targeting preventive interventions to those at high risk. [ABSTRACT FROM AUTHOR]

This raises the question whether the previous phase III trials, which were generally neutral, were simply performed too soon with insufficient development of combinations of effective interventions, and the current studies prepare the ground for large scale phase III trials with a higher chance of success. But while the SMARRT trial targets persons between 70 and 89, the AIBL and MYB studies target much younger populations of over 60 and 55-77, respectively [[5]]. Although the SMARRT pilot trial will use change in cognitive functioning for the sample size calculation for the full-scale trial, it will potentially be able to power for all-cause dementia due to the target age range of 70-89, depending on the expected effect size and planned study duration of the full trial. The AIBL proof of concept for sustainable adherence, the carefully designed pilot study necessary for a proper sample size calculation in SMARRT, and the ambitious MYB study may all inspire future dementia prevention study designs. [Extracted from the article]

In the hope of future treatments to prevent or slow down the disease, there is a strong movement towards an ever‐earlier detection of Alzheimer's disease (AD). In conjunction with scientific developments, this has prompted a reconceptualization of AD, as a slowly progressive pathological process with a long asymptomatic phase. New concepts such as 'preclinical' and 'prodromal' AD have been introduced, raising a number of conceptual and ethical questions. We evaluate whether these new concepts are theoretically defensible, in light of theories of health and disease, and whether they should be understood as disease or as an at‐risk state. We introduce a pragmatic view on disease concepts and argue that an evaluation of the reconceptualization of AD should also take its aims and effects into account, and assess their ethical acceptability. The reconceptualization of AD is useful to coordinate research into preventive strategies, and may potentially benefit future patients. However, in the short term, early detection and labelling of 'preclinical AD' can potentially harm people. Since there is no treatment available and the predictive value is unclear, it may only create a group of 'patients‐in‐waiting' who may suffer from anxiety, uncertainty and stigmatization, but will never actually develop dementia. We conclude that only if the promise of preventive medication materializes, will the reconceptualization of AD turn out unequivocally to be for the better. Otherwise, the reconceptualization may do more harm than good. [ABSTRACT FROM AUTHOR]

Background: Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to be bringing about this effect. The aim of this study was to estimate the age-specific dementia incidence trend in primary care records from a large population in the Netherlands.Methods and Findings: A dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRNs) across the country. Data regarding dementia incidence were obtained using general-practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 y and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people for the years 1992 to 2014, corresponding to over 4 million person-years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95% CI 0.5% to 3.8%), and incidence rates were 1.08 (95% CI 1.04 to 1.13) times higher for women compared to men. Despite their relatively low numbers of person-years, the highest age groups contributed most to the increasing trend. There was no significant overall change in incidence rates since the start of a national dementia program in 2003 (-0.025; 95% CI -0.062 to 0.011). Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis by general practitioners in electronic health records, and needs to be taken into account when interpreting the data.Conclusions: Within the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate a dramatic absolute increase in dementia occurrence over the years to come. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular risk factors are associated with an increased risk of dementia. We assessed whether a multidomain intervention targeting these factors can prevent dementia in a population of community-dwelling older people. Methods: In this open-label, cluster-randomised controlled trial, we recruited individuals aged 70-78 years through participating general practices in the Netherlands. General practices within each health-care centre were randomly assigned (1:1), via a computer-generated randomisation sequence, to either a 6-year nurse-led, multidomain cardiovascular intervention or control (usual care). The primary outcomes were cumulative incidence of dementia and disability score (Academic Medical Center Linear Disability Score [ALDS]) at 6 years of follow-up. The main secondary outcomes were incident cardiovascular disease and mortality. Outcome assessors were masked to group assignment. Analyses included all participants with available outcome data. This trial is registered with ISRCTN, number ISRCTN29711771. Findings: Between June 7, 2006, and March 12, 2009, 116 general practices (3526 participants) within 26 health-care centres were recruited and randomly assigned: 63 (1890 participants) were assigned to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6·7 years (21 341 person-years). Dementia developed in 121 (7%) of 1853 participants in the intervention group and in 112 (7%) of 1601 participants in the control group (hazard ratio [HR] 0·92, 95% CI 0·71-1·19; p=0·54). Mean ALDS scores measured during follow-up did not differ between groups (85·7 [SD 6·8] in the intervention group and 85·7 [7·1] in the control group; adjusted mean difference -0·02, 95% CI -0·38 to 0·42; p=0·93). 309 (16%) of 1885 participants died in the intervention group, compared with 269 (16%) of 1634 participants in the control group (HR 0·98, 95% CI 0·80-1·18; p=0·81). Incident cardiovascular disease did not differ between groups (273 [19%] of 1469 participants in the intervention group and 228 [17%] of 1307 participants in the control group; HR 1·06, 95% CI 0·86-1·31; p=0·57). Interpretation: A nurse-led, multidomain intervention did not result in a reduced incidence of all-cause dementia in an unselected population of older people. This absence of effect might have been caused by modest baseline cardiovascular risks and high standards of usual care. Future studies should assess the efficacy of such interventions in selected populations. Funding: Dutch Ministry of Health, Welfare and Sport; Dutch Innovation Fund of Collaborative Health Insurances; and Netherlands Organisation for Health Research and Development. [ABSTRACT FROM AUTHOR]

Background: In patients with a space-occupying middle cerebral artery (MCA) infarct surgical decompression reduces the risk of death, but increases the chance of survival with severe disability. We assessed quality of life (QoL), symptoms of depression, and caregiver burden at long-term follow-up. Methods: Patients treated in two academic centres between 2007 and 2012 were included. Follow-up was at least six months. Patients and caregivers were interviewed separately. QoL was assessed with a visual analogue scale and the 36-item Short-Form health survey (SF-36); depression with the Hospital Anxiety and Depression Scale; and caregiver burden with the Caregiver Strain Index. Results: Twenty five patients were enrolled, of whom seven had an infarct in the dominant hemisphere. After a median follow-up of 26 months (IQR 11-46) the median SF-36 mental component score was 54.4 (IQR 45-60), indicating a mental QoL comparable to that in the general population. The median SF-36 physical component score was 32.7 (IQR 22-38), indicating a worse physical QoL. Dominance of the hemisphere did not influence QoL. 79 % of patients and 65 % of caregivers would, in retrospect, again choose for surgery. 26 % of patients had signs of depression and 64 % of caregivers were substantially burdened in their daily life. Conclusions: Mental QoL after surgical decompression for space-occupying MCA infarct is comparable to that in the general population, whereas physical QoL is worse. Dominance of the hemisphere did not influence QoL. The majority of caregivers experience substantial burden. Most patients and caregivers stand by their decision for hemicraniectomy. [ABSTRACT FROM AUTHOR]

Midlife hypertension is an important risk factor for cognitive impairment and dementia, including Alzheimer's disease. We investigated the effects of long-term treatment with two classes of antihypertensive drugs to determine whether diverging mechanisms of blood pressure lowering impact the brain differently. Spontaneously hypertensive rats (SHR) were either left untreated or treated with a calcium channel blocker (amlodipine) or beta blocker (atenolol) until one year of age. The normotensive Wistar Kyoto rat (WKY) was used as a reference group. Both drugs lowered blood pressure equally, while only atenolol decreased heart rate. Cerebrovascular resistance was increased in SHR, which was prevented by amlodipine but not atenolol. SHR showed a larger carotid artery diameter with impaired pulsatility, which was prevented by atenolol. Cerebral arteries demonstrated inward remodelling, stiffening and endothelial dysfunction in SHR. Both treatments similarly improved these parameters. MRI revealed that SHR have smaller brains with enlarged ventricles. In addition, neurofilament light levels were increased in cerebrospinal fluid of SHR. However, neither treatment affected these parameters. In conclusion, amlodipine and atenolol both lower blood pressure, but elicit a different hemodynamic profile. Both medications improve cerebral artery structure and function, but neither drug prevented indices of brain damage in this model of hypertension. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined cerebral damage in adults with Tetralogy of Fallot (TOF), a common cyanotic congenital heart disease, using neuropsychological examination and structural magnetic resonance imaging (MRI). The study used univariate logistic regression to evaluate factors related to cerebral damage. Results showed that structural cerebral damage and cognitive impairment are common with adult patients with TOF.

Epidemiological studies have consistently shown that vascular risk factors including hypertension, diabetes, obesity, hypercholesterolemia, smoking, and lack of physical exercise are associated with an increased risk of cognitive decline and dementia. Neuroradiological and neuropathological studies have confirmed the importance of cerebrovascular lesions in the etiology of late onset dementia. We have reviewed the literature and conclude that up until now randomized controlled clinical trials targeting individual risk factors and assessing cognitive decline or dementia as an outcome have not convincingly shown that treatment of vascular risk factors can actually prevent or postpone cognitive decline and dementia. New studies targeting several vascular risk factors at the same time and using cognitive decline or dementia as primary outcome might answer the question whether cognitive decline can really be postponed or even prevented. The design of such studies is not straightforward and long follow-up is required. In this review we discuss several pertinent methodological issues that need to be addressed to achieve an optimal design of new randomized controlled trials. [ABSTRACT FROM AUTHOR]

The focus of most of the research on Alzheimer's disease in the last decades has been on senile plaques and neurofibrillary tangles. The vast majority of patients with Alzheimer's disease are over 75 years of age, whereas most of the research focuses on younger subjects. To consider old-age dementia as a homogenous well-defined condition ignores the complexity of this condition and limits the development of new diagnostic methods, preventive strategies, or treatment strategies that could be widely applicable in daily practice in the majority of the older patients. The current research on biomarkers focuses on correlates of plaques and tangles, which are poor markers in older dementia subjects. Acknowledging that dementia in old age is an essentially different condition from dementia at relatively younger age is needed and should lead to new approaches in dementia research. [ABSTRACT FROM AUTHOR]

The focus of most of the research on Alzheimer's disease in the last decades has been on senile plaques and neurofibrillary tangles. The vast majority of patients with Alzheimer's disease are over 75 years of age, whereas most of the research focuses on younger subjects. To consider old-age dementia as a homogenous well-defined condition ignores the complexity of this condition and limits the development of new diagnostic methods, preventive strategies, or treatment strategies that could be widely applicable in daily practice in the majority of the older patients. The current research on biomarkers focuses on correlates of plaques and tangles, which are poor markers in older dementia subjects. Acknowledging that dementia in old age is an essentially different condition from dementia at relatively younger age is needed and should lead to new approaches in dementia research. [ABSTRACT FROM AUTHOR]

Abstract: Recent epidemiological studies have indicated numerous associations between vascular and lifestyle related risk factors and incident dementia. However, evidence from randomised controlled trials (RCT) showing effectiveness of interventions aimed at these risk factors in preventing or postponing dementia onset is still lacking. Three large RCTs on multi-component interventions to prevent dementia (preDIVA, FINGER, MAPT) have been initiated in Europe to address these issues. Irrespective of some methodological differences, all three studies target cardiovascular and lifestyle related risk factors. Collaboration within the newly founded ‘European Dementia Prevention Initiative’ (EDPI) will allow for a comprehensive exploration of optimal target population, intervention and outcome measures, which are currently unknown. Combining data of the ongoing studies and running simulation analyses will facilitate determining the optimal design including accurate sample-size calculations for future multi-national clinical trials on dementia prevention. Interventions aiming at dementia prevention should be pragmatic and easy to implement on a large scale in different health care systems, without generating high additional costs or burden on participants or physicians. As the optimal age for intervention precedes the optimal age for outcome assessment, traditional trial designs might lead to suboptimal timing of either of the two. Separation of intervention and outcome assessment in time is a potential solution, but requires studies with very long follow-up. International collaboration of research groups with experience in dementia prevention studies and well-organised logistics for these major projects is pivotal to success for future large-scale dementia prevention studies. Founding of EDPI is an important first step in this direction. [Copyright &y& Elsevier]

Alzheimer's disease (AD) pathology is accompanied by abnormalities of the microvasculature. Despite the potential importance of morphometric changes in the cortical capillary network on neuronal dysfunction and cognitive impairment, few autopsy studies have addressed this issue. In the present study, we investigated morphological microvascular changes and capillary length density (CLD) in ten well-characterized AD patients compared to ten age-matched controls using virtual isotropic hemispheres. The CLD in the temporal cortex was increased by 33% in AD patients compared to controls (p=0.04), whereas CLD in the occipital cortex was unchanged. An increase of CLD was correlated to a decrease of cortical diameter in the temporal cortex (Pearson's r -0.62, p=0.003), suggesting that the increase in temporal CLD results from, or contributes to cortical atrophy. In the occipital cortex, more string vessels, probably remnants of degenerated capillaries, were observed in AD patients than in controls (p=0.004). An exploratory analysis suggests co-localization of Aβ and string vessels. Our data indicate that morphometric changes in the cortical capillary network occur in AD in a region-specific manner and may be related to cortical atrophy in the affected regions. [ABSTRACT FROM AUTHOR]

Cerebral amyloid angiopathy (CAA) is a common but often asymptomatic disease, characterized by deposition of amyloid in cerebral blood vessels. We describe the successful treatment of CAA encephalopathy with dexamethasone in a patient with CAA-related inflammation causing subacute progressive encephalopathy and seizures, which is an increasingly recognized subtype of CAA. The two pathological subtypes of CAA-related inflammation are described and a review of the literature is performed concerning immunosuppressive treatment of CAA-related inflammation with special attention to its pathological subtypes. Immunosuppressive therapy appears to be an appropriate treatment for CAA encephalopathy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To investigate whether vascular care slows dementia progression in patients with Alzheimer's disease with cerebrovascular lesions on neuroimaging. DESIGN: Multicenter randomized controlled clinical trial with 2-year follow-up. SETTING: Neurological and geriatric outpatient clinics in 10 Dutch hospitals: three academic, five teaching, and two midsize community hospitals. PARTICIPANTS: One hundred thirty community-dwelling patients with mild dementia fulfilling clinical criteria for Alzheimer's disease with cerebrovascular lesions on neuroimaging. INTERVENTION: Patients randomized to vascular care were treated according to strict guidelines for hypercholesterolemia and hypertension. Acetylsalicylic acid, folic acid, and pyridoxine were prescribed. During visits every 3 months special attention was paid to smoking cessation, losing weight, and stimulating physical exercise. MEASUREMENTS: Primary outcome was disability, measured according to the Interview for Deterioration in Daily activities in Dementia (IDDD). Secondary outcomes were changes on the Mini-Mental State Examination (MMSE), the Revised Memory and Behavioural Problems Checklist (RMBPC), a composite measure of “poor outcome” (death, institutionalization, or severe clinical decline), and costs. RESULTS: Patients in the vascular and standard care condition declined equally on the IDDD (13.7 vs 11.0 points; difference 2.7, 95% confidence interval =−3.1–8.6). There was no treatment effect on the MMSE or RMBPC. There were no differences in institutionalization rate, “poor outcome” (41.4% vs 35.4%, P=.50), or costs. In the intervention group, there were three intracerebral hemorrhages and one gastrointestinal hemorrhage, versus none in the control group. CONCLUSION: Multicomponent vascular care, combining pharmacological and nonpharmacological interventions, does not slow decline in patients with Alzheimer's disease with cerebrovascular lesions. [ABSTRACT FROM AUTHOR]

Objectives While ethnic minorities in Europe are disproportionally affected by cardiovascular disease (CVD), little is known about how general practitioners (GPs) perceive differences in risk or care needs across ethnic minority groups. Therefore, we explored GPs' views on whether ethnicity influences cardiovascular risk, whether a culturally sensitive approach is warranted, on potential barriers in the provision of such care, and to find potential opportunities to improve cardiovascular prevention for these groups. Methods We conducted a qualitative study by interviewing GPs practising in The Netherlands. The interviews were semistructured, audio-recorded, and analysed by 2 researchers using thematic analysis. Results We interviewed 24 Dutch GPs (50% male). GPs' views on the impact of ethnicity on CVD risk varied widely, yet it was generally recognized as a relevant factor in cardiovascular prevention for most minority groups, prompting earlier case-finding of high-risk patients. While GPs were aware of sociocultural differences, they emphasized an individualized approach. Perceived limitations were language barriers and unfamiliarity with sociocultural customs, leading to a need for continuing medical education on culturally sensitive care and reimbursement of telephone interpreting services. Conclusion Dutch GPs have differing views on the role of ethnicity in evaluating and treating cardiovascular risk. Despite these differences, they emphasized the importance of a personalized and culturally sensitive approach during patient consultations and expressed a need for continuing medical education. Additional research on how ethnicity influences CVD risk may strengthen cardiovascular prevention in increasingly diverse primary care populations. [ABSTRACT FROM AUTHOR]

An increasing number of people seek medical attention for mild cognitive symptoms at older age, worried that they might develop Alzheimer's disease. Some clinical practice guidelines suggest offering biomarker testing in such cases, using a brain scan or a lumbar puncture, to improve diagnostic certainty about Alzheimer's disease and enable an earlier diagnosis. Critics, on the other hand, point out that there is no effective Alzheimer treatment available and argue that biomarker tests lack clinical validity. The debate on the ethical desirability of biomarker testing is currently polarized; advocates and opponents tend to focus on their own line of arguments. In this paper, we show how the method of reflective equilibrium (RE) can be used to systematically weigh the relevant arguments on both sides of the debate to decide whether to offer Alzheimer biomarker testing. In the tradition of RE, we reflect upon these arguments in light of their coherence with other argumentative elements, including relevant facts (e.g. on the clinical validity of the test), ethical principles, and theories on societal ideals or relevant concepts, such as autonomy. Our stance in the debate therefore rests upon previously set out in-depth arguments and reflects a wide societal perspective. [ABSTRACT FROM AUTHOR]

The article focuses on the use of cholinesterase inhibitors (CEIs) in the treatment of dementia. It notes that only 5% to 15% of patients with Alzheimer's disease (AD) truly benefit from CEIs. It stresses that the failure of pharmaceutical companies to provide access to data that were generated with the help of dementia patients and their caregivers violates their trust and hinders the rational use of CEIs by future dementia patients.

Visit-to-visit blood pressure (BP) variability is a risk factor for cardiovascular disease and cognitive decline. Our aim was to assess the association between visit-to-visit BP variability and progression of white matter hyperintensities (WMH). Post-hoc analysis in the magnetic resonance imaging substudy of the randomized controlled trial prevention of dementia by intensive vascular care. Community-dwelling people age 70–78 years with hypertension. Participants had 3 to 5 twice yearly BP measurements and 2 magnetic resonance imaging scans at 3 and 6 years follow-up. We used linear regression adjusted for age, sex, WMH at scan 1, (change in) total brain volume, and cardiovascular risk factors. Among the 122 participants, there was a modest association between visit-to-visit systolic BP variability and WMH progression [beta = 0.03 mL/y per point increase in variability, 95% confidence interval (CI) 0.00–0.05, P =.058]. Additional adjustment for slope in systolic BP reduced the associated P value to.043. Visit-to-visit diastolic BP variability was not associated with WMH progression (beta = 0.01 mL/y, 95% CI −0.02 to 0.03, P =.68). Visit-to-visit pulse pressure variability was associated with WMH progression (beta 0.03 mL/y, 95% CI 0.01–0.05, P <.01). Higher visit-to-visit systolic BP and pulse pressure variability is associated with more progression of WMH among people age 70–78 years with hypertension. Interventions to reduce visit-to-visit BP variability may be most effective in people with low WMH burden. [ABSTRACT FROM AUTHOR]

Background and Objectives The meaning of Alzheimer's disease (AD) is changing in research. It now refers to a pathophysiological process, regardless of whether clinical symptoms are present. In the lay literature, on the other hand, AD is understood as a form of dementia. This raises the question of whether researchers and the lay audience are still talking about the same thing. If not, how will these different understandings of AD shape perspectives on (societal) needs for people with AD? Research Design and Methods We use framing analysis to retrieve the understandings of the term AD that are upheld in the research literature and in national Dutch newspaper articles. We make explicit how the framings of AD steer our normative attitudes toward the disease. Results In the analyzed research articles, AD is framed as a pathological cascade, reflected by biomarkers, starting in cognitively healthy people and ending, inevitably, in dementia. In the lay literature, AD is used as a synonym for dementia, and an AD diagnosis is understood as an incentive to enjoy "the time that is left." Discussion and Implications The two different uses of the term AD in research and in the lay literature may result in misunderstandings, especially those research framings that falsely imply that people with AD biomarkers will inevitably develop dementia. Adoption of the research understanding of AD in clinical practice will have normative implications for our view on priority setting in health care. For example, it legitimizes biomarker testing in people without dementia as improving "diagnostic" certainty. [ABSTRACT FROM AUTHOR]

Background: Hope for future treatments to prevent or slow down dementia motivates researchers to strive for ever-earlier diagnoses of Alzheimer's disease (AD) based on biomarkers, even before symptoms occur. But is a biomarker-based early diagnosis desirable in clinical practice?Objective: This study explores the ethical considerations that shape current clinical practice regarding early AD diagnostics and the use of biomarkers.Methods: In this qualitative study, Dutch physicians were interviewed. Topics included physicians' views concerning early AD diagnosis in persons with no or mild cognitive impairment, physicians' considerations regarding current and expected future practices of early AD diagnosis, the use of biomarkers, and the use of the concepts preclinical and prodromal AD. We analyzed the transcripts using directed content analysis.Results: 15 general practitioners, neurologists, and geriatricians in the Netherlands were interviewed. Most of them interpreted an early AD diagnosis with an early diagnosis of dementia. We identified six clusters of considerations sometimes in favor but most often against pursuing an early AD diagnosis in people with no or mild cognitive impairment that influence physicians' diagnostic decision-making: preferences and characteristics of persons, test characteristics, impact on care, type of setting, disease concepts, and issues on a societal level.Conclusion: The discussion concerning an early AD diagnosis based on biomarkers which is widely held in the scientific field, has not entered clinical practice structurally. A biomarker-based early diagnosis does not fit within Dutch physicians' views on what good care for people with no, subjective, or mild cognitive impairment should entail. [ABSTRACT FROM AUTHOR]

The article presents information on a research study on dementia, focusing on mild cognitive impairment. It states that mild cognitive disorder is an early stage of dementia. There are chances that the intensity of this mental disease does not increase, and the patient gradually attains normal cognition.

Early 2018 saw the release of new diagnostic guidance on Alzheimer's disease from the National Institute on Ageing and the Alzheimer's Association (NIA-AA). This proposed research framework represents a fundamental change in how we think about Alzheimer's disease, moving from diagnosis based on clinical features to diagnosis based solely on biomarkers. These recommendations are contentious and have important implications for patients, clinicians, policy makers and the pharmaceutical industry. In this commentary, we offer a summary of the NIA-AA research framework. We then focus on five key areas: divorcing neuropathology from the clinical syndrome; the emphasis placed on one dementia subtype; validity of available biomarkers; the changing meaning of the term 'Alzheimer's disease'; and the potential for a research framework to influence clinical practice. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "What Do We Mean By Alzheimer's Disease?," by M. Richards

A response by Edo Richard and Willem A. Van Gool to a letter to the editor about their article "Vascular care in patients with Alzheimer’s disease with cerebrovascular lesions-a randomized clinical trial” in a previous issue is presented.

The article discusses a study on the usefulness of data from magnetic resonance imaging to improve the prediction of dementia incident, by Blossom C. M. Stephan and colleagues, which appeared within the issue. Topics covered include the unclear objective for predicting dementia in older people without cognitive complaints and the complexity of the interpretation of findings on the discrimination performance in dementia.

More and more frequently, clinical trials for Alzheimer disease (AD) are targeting cognitively unimpaired individuals who are at increased risk of developing the disease. It is not always clear whether AD biomarker information should be disclosed to research participants: on the one hand, research participants may be interested in learning this information because of its perceived utility, but on the other hand, learning this information may be harmful, as there are very few effective preventive or therapeutic options available for AD. In this article, we bring together three separate sets of ethical guidance literature: on the return of individual research results, on an individual's right to access personal data, and on transparent enrollment into clinical trials. Based on these literatures, we suggest policies for the disclosure of AD biomarker test results in longitudinal observational cohort studies, clinical trials, and hybrid research projects, such as the European Prevention of Alzheimer's Dementia (EPAD) project, in which we served as an ethics team. We also present and critically discuss recommendations for disclosure of AD biomarkers in practice. We underscore that, as long as the clinical validity of AD biomarkers remains limited, there are good reasons to avoid actively disclosing them to cognitively unimpaired research participants. [ABSTRACT FROM AUTHOR]

Background: Although by definition a transient ischemic attack (TIA) lasts less than 24 h, many patients experience cognitive complaints beyond focal symptom resolution. However, their prevalence, causes and profile are unclear. We therefore performed a systematic review on cognitive impairment after TIA. Summary: Medline and Embase were searched for relevant studies. Risk of bias was assessed, and data synthesis was performed according to the severity of cognitive impairment. Thirteen studies were included, with considerable heterogeneity concerning methods and timing of cognitive testing. Confounding, detection bias and attrition were the main causes of a high risk of bias in several studies. The prevalence of post-TIA mild cognitive impairment ranged from 29 to 68%. Severe cognitive impairment was found in 8-22% of patients. Studies using a cognitive screening instrument and those performed shortly after TIA or several years later, reported the highest frequencies of impairment. Patients evaluated with a screening tool were substantially older than those who underwent a full neuropsychological assessment (weighted mean age difference 10.9 years). Based on limited data, the post-TIA cognitive profile showed prominent executive function deficits. Insufficient data refrained us from drawing conclusions on causality. The few studies that reported neuroimaging results found a minor correlation with cognitive impairment. Key Messages: Mild cognitive impairment is present in more than a third of the TIA patients and has a profile comparable with vascular cognitive impairment. Reported rates of post-TIA cognitive impairment are highly variable and higher frequencies are found with cognitive screening tools. Considerable heterogeneity and insufficient data limit further conclusions about potential causative factors. [ABSTRACT FROM AUTHOR]

The controversial approval in June 2021 by the Food and Drug Administration (FDA) of aducanumab (marketed as Aduhelm), Biogen's monoclonal antibody for patients with Alzheimer's disease, raises significant concerns for the dementia field and drug approval process, considering its lack of adequate evidence for clinical efficacy, safety issues, and cost. On 15 December 2021, an international group of clinicians, basic science experts, psychological and social science researchers, lay people with lived experience of dementia, and advocates for public health met to discuss making a recommendation for whether aducanumab's approval should be withdrawn. Attendees considered arguments both in favor of and in opposition to withdrawal and voted unanimously to recommend that the FDA withdraw its approval for aducanumab and to support the Right Care Alliance's filing of a formal Citizen Petition to this effect. [ABSTRACT FROM AUTHOR]

Background: Sporadic cerebral amyloid angiopathy (sCAA) research of the past decade has increasingly focused on developing biomarkers that allow for an earlier and more accurate sCAA-diagnosis. Considering that sCAA does not have treatment options available (yet), more fundamental questions concerning the desirability of using such early-sCAA biomarkers in clinical practice need to be addressed.Objective: In this qualitative interview study, we aim to explore the views of vascular neurologists on the purpose and possible consequences of an earlier and more accurate sCAA-diagnosis, using new biomarkers.Methods: Vascular neurologists from around the world were approached via email and interviewed via video call. Topics included views on current sCAA diagnostic practice, considerations on the use of new biomarkers, and expectations and hopes for the future. All interviews were transcribed ad verbatim using a transcription program (Otter.ai). Transcripts were analyzed using inductive content analysis.Results: We interviewed 14 vascular neurologists. Views regarding the desirability of new sCAA-biomarkers differed substantially between interviewees as to when and in whom these biomarkers could be of benefit in clinical practice. These differences were mainly reported with regards to prognosis, risk stratification, and biological precision, between general stroke neurologists and neurologists with specific sCAA-expertise.Conclusion: Views on the use of sCAA-biomarkers in clinical practice differ substantially between vascular neurologists. There is particularly no consensus regarding when, and in whom sCAA biomarkers could be useful in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Cognitive diagnostic work-up in primary care is not always physically feasible, owing to chronic disabilities and/or travel restrictions. The identification of dementia might be facilitated with diagnostic instruments that are time efficient and easy to perform, as well as useful in the remote setting. We assessed whether the Telephone Interview for Cognitive Status (TICS) might be a simple and accurate alternative for remote diagnostic cognitive screening in primary care.Methods: We administered the TICS (range, 0-41) for 810 of 1,473 older people aged 84.5 (SD, 2.4) years. We scrutinized electronic health records for participants with TICS scores ≤30 and for a random sample of participants with TICS scores >30 for a dementia diagnosis using all data from the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial for 8-12 years of follow-up. We used multiple imputation to correct for verification bias.Results: Of the 810 participants, 155 (19.1%) had a TICS score ≤30, and 655 (80.9%) had a TICS score >30. Electronic health records yielded 8.4% (13/154) dementia diagnoses for participants with TICS ≤30 vs none with TICS >30. Multiple imputation for TICS >30 yielded a median of 7/655 (1.1%; interquartile range, 5-8) estimated dementia cases. After multiple imputation, the optimal cutoff score was ≤29, with mean sensitivity 65.4%, specificity 87.8%, positive predictive value 11.9%, negative predictive value 99.0%, and area under the curve 77.4% (95% CI, 56.3%-90.0%).Conclusions: In the present older population, the TICS performed well as a diagnostic screening instrument for excluding dementia and might be particularly useful when face-to-face diagnostic screening is not feasible in family practice or research settings. The potential reach to large numbers of people at low cost could contribute to more efficient medical management in primary care. [ABSTRACT FROM AUTHOR]

Consistent cerebral blood flow (CBF) is fundamental to brain function. Cerebral autoregulation ensures CBF stability. Chronic hypertension can lead to disrupted cerebral autoregulation in older people, potentially leading to blood pressure levels interfering with CBF. This study tested whether low BP and AHD use are associated with contemporaneous low CBF, and whether longitudinal change in BP is associated with change in CBF, using arterial spin labelling (ASL) MRI, in a prospective longitudinal cohort of 186 community-dwelling older individuals with hypertension (77 ± 3 years, 53% female), 125 (67%) of whom with 3-year follow-up. Diastolic blood pressure, systolic blood pressure, mean arterial pressure, and pulse pressure were assessed as blood pressure parameters. As additional cerebrovascular marker, we evaluated the ASL signal spatial coefficient of variation (ASL SCoV), a measure of ASL signal heterogeneity that may reflect cerebrovascular health. We found no associations between any of the blood pressure measures and concurrent CBF nor between changes in blood pressure measures and CBF over three-year follow-up. Antihypertensive use was associated with lower grey matter CBF (−5.49 ml/100 g/min, 95%CI = −10.7|−0.27, p = 0.04) and higher ASL SCoV (0.32 SD, 95%CI = 0.12|0.52, p = 0.002). These results warrant future research on the potential relations between antihypertensive use and cerebral perfusion. [ABSTRACT FROM AUTHOR]

Background: Previous estimates of the lifetime risk of dementia are restricted to older age groups and may suffer from selection bias. In this study, we estimated the lifetime risk of dementia starting at birth using nationwide integral linked health register data.Methods: We studied all deaths in The Netherlands in 2017 (n = 147 866). Dementia was assessed using the cause-of-death registration, individually linked with registers covering long-term care, specialized mental care, dispensed medicines, hospital discharges and claims, and primary care. The proportion of deaths with dementia was calculated for the total population and according to age at death and sex.Results: According to all data sources combined, 24.0% of the population dies in the presence of dementia. This proportion is higher for females (29.4%) than for males (18.3%). Using multiple causes of death only, the proportion with dementia is 17.9%. Sequential addition of long-term care and hospital discharge data increased the estimate by 4.0 and 1.5%-points, respectively. Further addition of dispensed medicines, hospital claims and specialized mental care data added another 0.6%-points. Among persons who die at age ≤65-70 years, the proportion with dementia is ≤6.2%. After age 70, the proportion rises sharply, with a peak of 43.9% for females and 33.1% for males at age 90-95 years.Conclusions: Around one-fourth of the Dutch population is diagnosed with dementia at some point in life and dies in the presence of dementia. It is a major challenge to arrange optimal care for this group. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) research is beginning to focus on early disease modification and prevention. The therapeutic pipeline includes a growing range of pharmacological interventions that could theoretically intervene with the underlying disease process. It is hoped that applying such interventions in a very early stage of the disease pathology, before the onset of motor symptoms or during its early stages, may prevent or delay further disease progression. To identify people in this early disease stage, criteria for 'prodromal PD' have been proposed—describing people with one or more specific features that jointly constitute a variably increased risk of developing clinically manifest PD. Here, we aim to draw lessons from the field of Alzheimer's research, which has followed a similar strategy over the last decade, including the expansion of the disease label to 'prodromal' stages. Importantly, none of the large and costly randomized-controlled trials aiming to slow down or prevent Alzheimer's dementia by targeting the alleged disease pathology, i.e., amyloid-β aggregation, resulted in detectable clinical effects. Lack of sufficiently robust phase 2 trial results before moving to phase 3 studies, suboptimal participant selection, insensitive outcomes, a too narrow target focus, and trial design flaws contributed to this disappointing outcome. We discuss the various similarities between these Alzheimer's and PD approaches, and review the design of prevention or early disease modification trials for both diseases including the potential for immunotherapy. Finally, we offer considerations to optimize the design of such trials in PD, benefiting from the lessons learned in Alzheimer's prevention research. [ABSTRACT FROM AUTHOR]

Objectives To determine the diagnostic accuracy of GPs' clinical judgement for diagnosing cognitive impairment and dementia in symptomatic people presenting to primary care. In primary care, general practitioners (GPs) unavoidably reach a clinical judgement about a patient as part of their encounter with patients, and so clinical judgement can be an important part of the diagnostic evaluation. [Extracted from the article]

Background: Pooling individual participant data to enable pooled analyses is often complicated by diversity in variables across available datasets. Therefore, recoding original variables is often necessary to build a pooled dataset. We aimed to quantify how much information is lost in this process and to what extent this jeopardizes validity of analyses results. Methods: Data were derived from a platform that was developed to pool data from three randomized controlled trials on the effect of treatment of cardiovascular risk factors on cognitive decline or dementia. We quantified loss of information using the R-squared of linear regression models with pooled variables as a function of their original variable(s). In case the R-squared was below 0.8, we additionally explored the potential impact of loss of information for future analyses. We did this second step by comparing whether the Beta coefficient of the predictor differed more than 10% when adding original or recoded variables as a confounder in a linear regression model. In a simulation we randomly sampled numbers, recoded those < = 1000 to 0 and those >1000 to 1 and varied the range of the continuous variable, the ratio of recoded zeroes to recoded ones, or both, and again extracted the R-squared from linear models to quantify information loss. Results: The R-squared was below 0.8 for 8 out of 91 recoded variables. In 4 cases this had a substantial impact on the regression models, particularly when a continuous variable was recoded into a discrete variable. Our simulation showed that the least information is lost when the ratio of recoded zeroes to ones is 1:1. Conclusions: Large, pooled datasets provide great opportunities, justifying the efforts for data harmonization. Still, caution is warranted when using recoded variables which variance is explained limitedly by their original variables as this may jeopardize the validity of study results. [ABSTRACT FROM AUTHOR]

Background: The shift to defining Alzheimer's disease (AD) as a biological continuum, which is characterized by the presence of biomarkers instead of clinical symptoms, has sparked a widespread debate. Insight into the given arguments and their underlying moral values is crucial to ensure well-considered and appropriate AD biomarker testing in the future.Objective: To critically review the arguments in favor of or against AD biomarker testing in people with no or mild cognitive impairment and to explicate their underlying moral values.Methods: Seven databases were systematically searched for publications mentioning arguments of interest. Arguments are identified using qualitative data-analysis and evaluated within an ethical framework.Results: Our search yielded 3,657 articles of which 34 met the inclusion criteria. We discuss the clusters of arguments separate from their evaluation and the assessment of the debate as a whole. The right to know, which derives from the moral value of respect for autonomy, is a central argument in favor of biomarker testing. On the other hand, fear of the disease and lack of a disease-modifying treatment may result in a negative balance of good over inflicted harms, which argues against its use.Conclusion: Critical evaluation and weighing of the given arguments in a specific context, within an ethical framework, demonstrates the necessity to differentiate between what we hope or expect from research and where we currently stand. While AD biomarkers may have an indispensable value for research, the current advantage for clinical practice appears limited. [ABSTRACT FROM AUTHOR]

Introduction: Primary cardiovascular prevention through simultaneously targeting multiple risk factors may be even more effective than single risk factor modification in older adults. The effects of multicomponent cardiovascular prevention on cardiovascular risk are explored.Study Design: Post hoc analysis of the cluster randomized Prevention of Dementia by Intensive Vascular care trial.Setting/participants: Community-dwelling older adults aged 70-78 years, free from cardiovascular disease at baseline (n=2,254, 63.9% of the Prevention of Dementia by Intensive Vascular care trial population).Intervention: Between 2006 and 2015, the intervention group received nurse-led vascular care every 4 months at the general practitioner practice, the control group received care as usual.Main Outcome Measures: Cardiovascular disease events and Systematic COronary Risk Evaluation in Older People (SCORE-OP), an index based on six risk factors for cardiovascular mortality. Effects were adjusted for clustering and assessed using mixed effects Cox proportional-hazard models and linear mixed models respectively.Results: There was no effect of the intervention on cardiovascular disease events (hazard ratio=0.99, 95% CI=0.71, 1.38). During a median follow-up of 6.1 years, SCORE-OP increased from 14.0% and 13.9% to 23.9% and 25.0% in the intervention and control group, respectively (adjusted mean difference in increment in SCORE-OP between the study groups 0.60%, 95% CI= -0.01, 1.20). Exploratory analyses showed a larger reduction of 2.4 mmHg (95% CI=0.9, 3.9) in systolic blood pressure and 1.9% (95% CI=0.4, 3.4) in current cigarette smoking in the intervention group compared with the control group.Conclusions: Multicomponent cardiovascular prevention did not improve the overall risk profile in older adults in a primary prevention setting, relative to usual care. However, exploratory analyses showed an effect on blood pressure and smoking cessation. Possibly, contrast between study groups was too small because of the Hawthorne (being part of a study) effect and increasing quality of (preventive) health care for older adults, to yield an effect on the risk profile. [ABSTRACT FROM AUTHOR]

Purpose: The Mini-Mental State Examination (MMSE) is one of the most widely used instruments to screen for cognitive deficits; however, this instrument alone is not sensitive enough to detect early symptoms of dementia. We aimed to investigate whether additionally using the Visual Association Test (VAT) improves the predictive value of the MMSE score for development of dementia.Methods: Analyses were based on data from 2,690 primary care patients aged 70 to 78 years who participated in the Prevention of Dementia by Intensive Vascular Care (preDIVA) trial. We assessed change in the 30-point MMSE score over 2 years and the VAT score at 2 years-dichotomized as perfect (6 points) or imperfect (≤5 points)-and evaluated the predictive values of these tests for a diagnosis of dementia in the subsequent 4 to 6 years. Data were analyzed with logistic regression analysis.Results: Patients having a decline of 2 points or more in total MMSE score over 2 years had an odds ratio of 3.55 (95% CI, 2.51-5.00) for developing dementia. Patients having the same decline in MMSE score plus an imperfect VAT score had an odds ratio of 9.55 (95% CI, 5.89-15.41) for developing dementia. A 1-point decline in MMSE score increased odds of dementia only when the VAT score was imperfect. Dementia risk for patients with a 2- or 3-point decrease in MMSE score and a perfect VAT score did not differ significantly from the average risk of the cohort as a whole.Conclusions: Administering the VAT in patients with a small decline on the MMSE over a 2-year period has substantial incremental value for identifying those at elevated risk for developing dementia. This simple test may help distinguish older adults who need further cognitive examination from those in whom a watchful waiting policy is justified. [ABSTRACT FROM AUTHOR]

Objective: To determine if autonomic dysfunction, cognitive disorders or axial disability are associated with white matter lesions (WML) in Parkinson disease (PD).Methods: We performed a retrospective cross-sectional review study on 204 consecutive PD patients who underwent cerebral MRI in our center between January 2012 and July 2016. For each patient, we scored the severity of WML and PV (periventricular) WML using the Fazekas score and using the ARWMC scale for WML and BG (basal ganglia) and clinical characteristics such as neurogenic orthostatic hypotension and cognitive function.Results: 204 PD patients were included of whom n = 53 (26.0%) had neurogenic orthostatic hypotension (nOH). The presence of nOH was significantly associated with the severity of WML as defined by the Fazekas score and the ARWMC scale. An ordinal regression model confirmed this association with an OR of 0.41 (95% CI 0.18-0.92: p = .03) and an OR of 0.39 (95% CI 0.17-0.88: p = .02). There were no significant associations between WML and other co-variables, including hypertension, dopaminergic medication use, Hoehn and Yahr stage, gender and cognitive decline.Conclusion: The presence of nOH is associated with WML severity in PD patients. [ABSTRACT FROM AUTHOR]