Criteria For Vascular Dementia Research Articles

Ventricular electrocardiographic signatures associated with dementia and plasma Alzheimer’ s biomarkers in older adults: The MIND‐China study

AbstractBackgroundCardiovascular risk factors and cardiovascular diseases (CVDs) have been linked with dementia. In addition, amyloid‐β (Aβ) is detected in the heart of patients with Alzheimer’s disease (AD). However, no population‐based studies have yet investigated the interrelationships of ventricular electrocardiographic (ECG) profiles (e.g., QT, JT, QRS intervals, and QRS axis angle) with dementia and plasma Alzheimer’s biomarkers.MethodThis population‐based cross‐sectional study included 5110 participants (age ≥65 years; 57.2% women) from the baseline assessments of the multimodal interventions to delay dementia and disability in rural China (MIND‐China) in March‐September 2018; of these, 1273 had data on plasma Aβ42, Aβ40, total‐tau, and neurofilament light chain (NfL) that were measured using the single molecule array (SIMOA) technology. Ventricular ECG parameters included QT, QTc, JT, JTc, QRS intervals, and QRS axis angle. The DSM‐IV criteria were followed for the diagnosis of dementia, the NIA‐AA criteria for AD, and NINDS‐AIREN criteria for vascular dementia (VaD). Data were analyzed using the general linear models, multinomial logistic models, and restricted cubic splines.ResultOf the 5110 participants, 296 (5.79%) were diagnosed with dementia (192 with AD; 93 with VaD). The multivariable‐adjusted odds ratios (95% CI) of dementia associated with the quartiles of QT interval were 1.00 (reference), 1.66 (1.11‐2.50), 1.93 (1.25‐3.00), and 1.78 (1.10‐2.91), respectively. QTc, JT, and JTc intervals had analogous associations with dementia, and these ventricular ECG parameters were significantly associated with an increased likelihood of AD and VaD. The restricted cubic spline model suggested a significant association of QRS axis left deviation with VaD. In the plasma biomarker subsample, JT and JTc intervals were associated with multivariable‐adjusted β coefficients (95% CI) of ‐0.15 (‐0.27‐ ‐0.03) and ‐0.11 (‐0.20‐ ‐0.01), respectively, for Aβ42/Aβ40 ratio. The multivariable‐adjusted β coefficients (95% CI) of plasma NfL associated with QT, JT, and JTc intervals were 0.04 (0.01‐0.08), 0.06 (0.02‐0.09), and 0.04 (0.01‐0.07), respectively.ConclusionVentricular ECG signatures for dementia and plasma Alzheimer’s biomarkers in rural‐dwelling older adults are characterized by altered ventricular repolarization and depolarization. These results support the view that Aβ metabolism and neurodegeneration might be involved in the associations of ventricular ECG profiles with dementia.

Is vascular cognitive impairment a distinct clinical entity?

The term Vascular Cognitive Impairment (VCI) was introduced to emphasise the important contribution of vascular pathology to any severity of cognitive impairment, ranging from subjective cognitive decline and mild cognitive impairment (MCI) to dementia. Although vascular pathology and Alzheimer's Disease (AD) is common in elderly individuals with and without cognitive impairment or dementia, pure vascular dementia (VaD) or AD is uncommon. Indeed, most patients with VaD or AD also have other types of pathology, the most common of which is a combination of AD and cerebrovascular disease (CeVD). Several different VCI criteria have been proposed. The more recent VASCOG, DSM-5 and VICCCS criteria may have greater sensitivity, modest concurrent validity and better predictive validity than older criteria such as the NINDS-AIREN and DSM-4 criteria for VaD. Importantly, diagnoses for vascular MCI can now be made which may be useful for clinical and research purposes which include establishing cognitive trajectories, prognostic biomarkers and better understanding of the underlying mechanisms. Vermiglio (2014) proposed several criteria for a clinical entity: 1) The clinical entity must possess an unambiguous definition; 2) It must represent a homogeneous patient group; 3) It must represent a perceived limitation for the patient and 4) It must facilitate diagnosis and intervention This presentation will discuss ways in which VCI fulfils these criteria. Refining the concept of VCI enables a better understanding of pathophysiology and aids in treatment efforts which is currently mainly through prevention by treating vascular diseases and other risk factors until the advent of disease-modifying treatments.

The Prevalence of Vascular Dementia in China: A Systematic Review and Meta-Analysis from 2009-2019.

Background:Vascular dementia (VD), as the second-largest type of dementia, is a serious stage of vascular cognitive impairment. It is significant to conduct retrospective epidemiological studies to characterize further the disease for public health. This study estimated the prevalence of VD among the population aged 18 yr and older in China.Methods:Epidemiological investigations on VD published in journals and covering the period from 1999 to 2019 were identified manually and online by using Chinese databases (such as Chinese BioMedical Literature Database, Chinese National Knowledge Infrastructure database, Chinese science-technology databases, and the Chinese Wan-fang and Chongqing VIP database) and English databases (such as PubMed, Elsevier Science Bibliographic Databases and Cochrane library). Studies were included if the diagnostic criteria for VD are clear and the quality of the included literature was evaluated using the quality evaluation criteria of epidemiological research methods. A random-effects model was employed according to the statistical test of homogeneity.Results:Twenty-six studies met the inclusion criteria, including 100,923 subjects and 977 VD patients. The pooled prevalence of VD was 0.96% (95% [confidence interval, CI] 0.63%∼2.1%). The prevalence of VD increased with increasing age. There was a higher prevalence of VD in the northeast China population, in urban areas and males.Conclusion:We stratified the included studies based on age, location, gender, and geographical distribution for prevalence. The prevalence of VD has slowly risen since 1999. It is obviously different between the North & South and urban &rural districts. While there are many benefits of systematic reviews, the methods presented have inherent limitations.

FUNCTIONAL NEUROMARKERS OF COGNITIVE IMPAIRMENT IN VASCULAR DEMENTIA: A CASE STUDY

Early diagnosis and monitoring of disease progression in patients with Vascular Dementia (VaD) have become vital in clinical practice, as disease modifying treatments for VaD become available. The goal of our research was to study cognitive impairment in a patient at an early stage of VaD. We evaluated latencies of the P3 GO and NOGO components of event-related potentials (ERPs), elicited in cued GO/NOGO tasks, as potential neuromarkers of cognitive im- pairment, as suggested by previous research. The patient, a right-handed, 53-year-old male with a college edu- cation, suffered a transient ischemic attack (TIA) in 2011. During this attack, which lasted for a few minutes, he was confused and had trouble speaking, trouble seeing in both eyes, difficulty walking, problems with balance and coordination, and strange behavior. Se - ven years later, in 2018, he was assessed using the HBI methodol- ogy, which consisted of recording (1) a 19-channel EEG in resting state (with eyes open and eyes closed), and (2) a cued GO/NOGO task, and then comparing the results with EEG spectra and Event- Related Potentials (ERPs) data from normative and patient data - bases. The patient died in 2019. Post-mortem studies confirmed cortical microhaemorrhages neuropathological criteria for VaD. We did not found deposits of hyperphosphorylated tau (HPτ) and Aβ, which fulfil the neuropathological criteria for AD. The parietal-temporal-occipital EEG power was significantly higher in all conditions in this subject in comparison to healthy controls, indicating idling of the corresponding areas. The amplitude and la- tency of the P3 GO wave were found to be intact in the subject, in- dicating normal posterior cortical functioning in the cognitive task. The latency of the P3 GO wave was found to be significantly higher in the subject, indicating impairment of engagement operations. In a GO/NOGO task, ERPs provide a useful tool for assessment of brain functioning in clinical settings.

The Vascular Behavioral and Cognitive Disorders criteria for vascular cognitive disorders: a validation study.

The Vascular Behavioral and Cognitive Disorders (VASCOG) criteria for vascular cognitive disorders were published in 2014, but their concurrent and predictive validity have not been examined. Participants (N=165, aged 49-86years) were from Sydney Stroke Study, a longitudinal study of post-stroke cognitive impairment and dementia. Diagnoses using the National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN), the Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), criteria for vascular dementia (VaD) were made by consensus at multidisciplinary case conferences. Diagnoses for mild vascular cognitive disorder (mVCD) and VaD using VASCOG, DSM-5 and the Vascular Impairment of Cognition Classification Consensus Study (VICCCS) criteria were made by two study authors. Agreement levels between criteria sets were examined using Cohen's kappa (κ). The ability of VaD diagnoses to predict mortality over 10years and of mVCD to predict dementia over 5years was investigated. The VASCOG criteria yielded rates of mVCD slightly lower than for DSM-5 and VICCCS. VaD rates were similar for all criteria, although slightly lower for DSM-IV. Agreement between the VASCOG, VICCCS and DSM-5 criteria was excellent for VaD and mVCD (κ=0.83-1.0), but lower for VaD between VASCOG and the other criteria (κ=0.47-0.63). VaD-based mortality predictions were similar for the VASCOG, VICCCS and DSM-5 criteria, and higher than those for other criteria. The prediction of incident dementia within 5years from mVCD was slightly lower with VASCOG criteria than with DSM-5 and VICCCS criteria. The VASCOG criteria have greater sensitivity, modest concurrent validity and better predictive validity than older criteria for VaD, but are comparable to DSM-5 and VICCCS criteria. Their operationalization and inclusion of a mild VCD category make them useful for clinical and research applications.

Pattern of cognitive deficits in vascular dementia.

Background & objectives:There is a paucity of literature on the cognitive profiles of vascular dementia (VaD) in India. The current study was undertaken to investigate the pattern of cognitive deficits in patients with VaD.Methods:Fifty patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders-IV criteria of dementia and National Institute of Neurological Disorders and Stroke - Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria for VaD were assessed using Mini Mental State Examination, Kolkata Cognitive Screening Battery and other relevant tests including magnetic resonance imaging of brain.Results:Twenty patients had small vessel dementia, whereas the least common was haemorrhagic dementia in four patients. In patients with small vessel dementia, apart from memory, all patients had problem in attention and executive function, whereas 12 patients had visuoconstructional deficit and eight patients had language problem. In a total of 12 patients with large vessel dementia, apart from memory, executive dysfunction and visuoconstructional deficit were noted in 10 patients, whereas attention deficit was noted in eight patients. Attention was found to be more involved in small-vessel dementia than large-vessel dementia though all had memory impairment (P<0.01).Interpretation & conclusions:Small vessel dementia was the commonest subtype of VaD in our study. Memory, attention and executive functions were predominantly affected in patients with VaD. Attention was significantly more involved in small vessel dementia than large vessel dementia. Further studies with large sample size need to be done in different regions of the country.

Atrial fibrillation, antithrombotic treatment, and cognitive aging: A population-based study.

ObjectiveTo examine the association of atrial fibrillation (AF) with cognitive decline and dementia in old age, and to explore the cognitive benefit of antithrombotic treatment in patients with AF.MethodsThis population-based cohort study included 2,685 dementia-free participants from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001–2004 to 2010–2013. AF was ascertained from clinical examination, ECG, and patient registry. Global cognitive function was assessed using the Mini-Mental State Examination. We followed the DSM-IV criteria for the diagnosis of dementia, the NINDS-AIREN (National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences) criteria for vascular dementia, and the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) criteria for Alzheimer disease. Data were analyzed using multiple linear mixed-effects and Cox regression models.ResultsWe identified 243 participants (9.1%) with AF at baseline. During the 9-year follow-up period, 279 participants (11.4%) developed AF and 399 (14.9%) developed dementia. As a time-varying variable, AF was significantly associated with a faster annual Mini-Mental State Examination decline (β coefficient = −0.24, 95% confidence interval [CI]: −0.31 to −0.16) and an increased hazard ratio (HR) of all-cause dementia (HR = 1.40, 95% CI: 1.11–1.77) and vascular and mixed dementia (HR = 1.88, 95% CI: 1.09–3.23), but not Alzheimer disease (HR = 1.33, 95% CI: 0.92–1.94). Among people with either prevalent or incident AF, use of anticoagulant drugs, but not antiplatelet treatment, was associated with a 60% decreased risk of dementia (HR = 0.40, 95% CI: 0.18–0.92).ConclusionAF is associated with a faster global cognitive decline and an increased risk of dementia in older people. Use of anticoagulant drugs may reduce dementia risk in patients with AF.

Validation Study of the Korean Version of the Brief Clinical Form of the Neuropsychiatric Inventory

Aim: This study aims to provide a brief questionnaire form of the Neuropsychiatric Inventory (NPI-Q) in Korean translated from the original NPI-Q that is intended for the evaluation of behavioral and psychological symptoms of dementia in routine clinical practice. Patients and Methods: We developed a Korean version of the NPI-Q (KNPI-Q) and compared subitems with those of the Korean version of the NPI (KNPI) in 63 dementia patients; 47 patients had been diagnosed with Alzheimer's disease with dementia, 8 with vascular dementia, and 8 with dementia with Lewy body disease. The diagnosis was based on the National Institute of Neurological and Communicative Disorders and Stroke - Alzheimer's Disease and Related Disorders Association criteria for possible and probable Alzheimer's disease and the International Statistical Classification of Diseases and Related Health Problems, 10th revision, criteria for vascular dementia and other dementing diseases. All patients received the Korean version of the Mini-Mental State Examination and the Clinical Dementia Rating within 1 month of the KNPI-Q. Results: Test-retest reliability of the KNPI-Q using a Pearson correlation index was r = 0.89 for the total symptom scale and r = 0.90 for the distress scale. The prevalence of analogous symptom ratings differed by less than 6.7%. Convergent validity between the KNPI-Q and the NPI using a Pearson correlation index was r = 0.879 for the total symptom scale and r = 0.92 for the distress scale. Conclusions: The KNPI-Q is a reliable and brief instrument that can be employed for screening in the evaluation of neuropsychiatric symptoms of dementia and associated caregiver distress. It may be suitable for use in general clinical practice and could be administered as a brief neuropsychiatric interview.

The prevalence of dementia subtypes in rural Tanzania.

The prevalence of dementia is predicted to increase rapidly in developing countries. Vascular risk factors may contribute to this rise. Our aim was to estimate the proportions of Alzheimer's disease (ADD) and vascular dementia (VAD) in a prevalent cohort of dementia cases in rural Tanzania. A two-stage door-to-door dementia prevalence study. Hai district, Tanzania In Phase I, the Community Screening Instrument for Dementia (CSI-D) was used to screen 1198 community-dwelling people for dementia. In Phase II, 168/184 (91.3%) of those with poor performance, 56/104 (53.8%) of those with intermediate performance and 72/910 (7.9%) of those with good performance on CSI-D were interviewed and diagnoses were made using the DSM-IV criteria. For subtype diagnosis, DSM-IV dementia criteria plus NINCDS-ADRDA criteria were used for ADD and NINDS-AIREN criteria for VAD. Other dementias were diagnosed by international consensus criteria. Diagnoses were confirmed or excluded by computerised tomography where clinically appropriate. Of 78 dementia cases, 38 (48.7%) were ADD and 32 (41.0%) were VAD. The crude prevalence of ADD was 3.7% (95% CI 2.5 to 4.9) and of VAD was 2.9% (95% CI 1.9 to 3.9). The age-adjusted prevalence was 3.0% (95% CI 1.8 to 4.2) for ADD and 2.6% (95% CI 1.6 to 3.6) for VAD. A previous diagnosis of diabetes mellitus was independently associated with greater odds of having VAD than ADD. VAD accounted for a greater proportion of dementia cases than expected. Further investigation and treatment of risk factors is required in this setting.

Neuropsychological assessment and cerebral vascular disease: The new standards

Vascular cognitive impairment (VCI) includes vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and mixed dementia. In clinical practice, VCI concerns patients referred for clinical stroke or cognitive complaint. To improve the characterization of VCI and to refine its diagnostic criteria, an international group has elaborated a new standardized evaluation battery of clinical, cognitive, behavioral and neuroradiological data which now constitutes the reference battery. The adaption of the battery for French-speaking subjects is reported as well as preliminary results of the on-going validation study of the GRECOG-VASC group [Clinical Trial NCT01339195]. The diagnostic accuracy of various screening tests is reviewed and showed an overall sub-optimal sensitivity (<0.8). Thus, the general recommendation is to perform systematically a comprehensive assessment in stroke patients at risk of VCI. Furthermore,the use of a structured interview has been shown to increase the detection of dementia. In addition to the well known NINDS-AIREN criteria of VaD, criteria of VCI have been recently proposed which are based on the demonstration of a cognitive disorder by neuropsychological testing and either history of clinical stroke or presence of vascular lesion by neuroimaging suggestive of a link between cognitive impairment and vascular disease. A memory deficit is no longer required for the diagnosis of VaD as it is based on the cognitive decline concerning two or more domains that affect activities of daily living. Both VaMCI and VaD are classified as probable or possible. These new criteria have yet to be validated. Considerable uncertainties remain regarding the determinant of VCI, and especially the lesion amount inducing VCI and VaD. The interaction between lesion amount and its location is currently re-examined using recent techniques for the analysis of MRI data. The high frequency of associated Alzheimer pathology is now assessable in vivo using amyloid imaging. The first studies showed that about a third of patients with VaD due to small vessel disease or with poststroke dementia have amyloid PET imaging suggestive of AD. These new techniques will examine the interaction between vascular lesions and promotion of amyloid deposition. Although results of these on-going studies will be available in few years, these data indicate that efforts should be done in clinical practice to reduce underdiagnosis of VCI; VCI should be examined using a specific protocol which will be fully normalized soon for French-speaking patients; the sub-optimal sensitivity of screening tests prompts to use a structured interview to grade Rankin scale and to perform systematically a comprehensive assessment in stroke patients at risk of VCI; poststroke dementia occurring after 3 months poststroke may be preventable by treatment of modifiable vascular risk factors and secondary prevention of stroke recurrence according to recent recommendations.

Nutrition and vascular dementia.

The objective of this review was to elucidate the relationship between VaD and various nutritional factors based on epidemiological studies. Vascular dementia (VaD) is the second most common type of dementia. The prevalence of VaD continues to increase as the US population continues to grow and age. Currently, control of potential risk factors is believed to be the most effective means of preventing VaD. Thus, identification of modifiable risk factors for VaD is crucial for development of effective treatment modalities. Nutrition is one of the main modifiable variables that may influence the development of VaD. A systematic review of literature was conducted using the PubMed, Web of Science, and CINAHL Plus databases with search parameters inclusive of vascular dementia, nutrition, and vascular cognitive impairment (VCI). Fourteen articles were found that proposed a potential role of specific nutritional components in VaD. These components included antioxidants, lipids, homocysteine, folate, vitamin B12, and fish consumption. Antioxidants, specifically Vitamin E and C, and fatty fish intake were found to be protective against VaD risk. Fried fish, elevated homocysteine, and lower levels of folate and vitamin B12 were associated with increased VaD. Evidence for dietary lipids was inconsistent, although elevated midlife serum cholesterol may increase risk, while late-life elevated serum cholesterol may be associated with decreased risk of VaD. Currently, the most convincing evidence as to the relationship between VaD and nutrition exists for micronutrients, particularly Vitamin E and C. Exploration of nutrition at the macronutrient level and additional long term prospective cohort studies are warranted to better understand the role of nutrition in VaD disease development and progression. At present, challenges in this research include limitations in sample size, which was commonly cited. Also, a variety of diagnostic criteria for VaD were employed in the studies reviewed, indicating the need for constructing a correct nosological definition of VaD for consistency and conformity in future studies and accurate clinical diagnosis of VaD.

Vascular dementia: Cognitive, functional and behavioral assessment. Recommendations of the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology. Part II.

Vascular dementia (VaD) is the most prevalent form of secondary dementia and the second most common of all dementias. The present paper aims to define guidelines on the basic principles for treating patients with suspected VaD (and vascular cognitive impairment - no dementia) using an evidence-based approach. The material was retrieved and selected from searches of databases (Medline, Scielo, Lilacs), preferentially from the last 15 years, to propose a systematic way to assess cognition, function and behavior, and disease severity staging, with instruments adapted for our milieu, and diagnosis disclosure. The present proposal contributes to the definition of standard diagnostic criteria for VaD based on various levels of evidence. It is noteworthy that only around half of the population of patients with vascular cognitive impairment present with dementia, which calls for future proposals defining diagnostic criteria and procedures for this condition.

Subcortical vascular dementia exists!

The year 2011 will be pivotal for research and care of patients with Alzheimer disease (AD). The 27-year-old diagnostic criteria1 that have defined AD as diagnosis of exclusion have undergone revision. Key features of these criteria include the use of biomarkers to support a diagnosis of AD. In particular, these biomarkers include both CSF and PET measures of β-amyloid (Aβ) pathology. While there is still considerable uncertainty about the factors responsible for the initiation and progression of AD, the use of in vivo measures of Aβ pathology has undoubtedly revolutionized research and will soon affect clinical diagnosis. One of the most problematic diagnostic questions has involved the interaction between AD and vascular pathology. For years clinicians have had access to imaging techniques such as CT and MRI that permit the evaluation of ischemic lesions. This has led to imaging-based criteria for vascular dementia. However, without an in vivo marker of Aβ pathology, understanding the contribution of AD pathology to persons diagnosed with vascular etiologies has largely relied upon autopsy. Many autopsy studies indicated that isolated subcortical vascular pathology is a relatively uncommon cause of dementia, with most such cases having moderate to severe plaque and tangle pathology as well.2 However, these autopsy studies are limited since they may …

Vascular Dementia: The Silent Epidemic: The Role of Statins

Synopsis: Vascular dementia (VAD) was described by Dr. Alzheimer more than a century ago, yet it is rarely discussed in the lay media. The increased use of imaging technology has heightened awareness of VAD despite disagreement on the criteria for VAD. Cerebrovascular disease is a heterogenous disorder. VAD is second in incidence to Alzheimer's disease (AD) and is being diagnosed with increasing frequency. Both VAD and AD share the risk factors of hypertension, insulin resistance, diabetes, and dyslipidemia.

Vascular Cognitive Disorder. A Biological and Clinical Overview

Although vascular dementia (VaD) represents the second most common cause of dementia after Alzheimer's disease (AD) in the elderly, and is referred as the "silent epidemic of the twenty-first century", there is still a controversy on terminology, classification and diagnostic criteria of VaD. The diagnosis of VaD resides in clinical criteria determining a cognitive impairment, the presence of cerebrovascular disease and, only in the case of post-stroke dementia or multi-infarct dementia, a temporal relationship between these. The search for a reliable biochemical tests helping in the diagnosis of VaD is so far not available. Several vascular risk factors have a role in the development of VaD and their identification and treatment are among the major aspects of management of VaD. A new line of research in this field is the study of genetic factors underlying vascular cognitive impairment which are: (1) genes predisposing to cerebrovascular disease, and (2) genes that influence brain tissue responses to cerebrovascular lesions. Evidence in favour of a coexistence of vascular and degenerative components in the pathogenesis of dementia in an elderly population comes from neuropathological and epidemiological studies. There is now a great debate whether VaD and AD are more than common coexisting unrelated pathologies and, instead, represent different results of synergistic pathological mechanisms. Preventive approaches aiming at reducing incident VaD by targeting patients at risk of cerebrovascular disease (primary prevention), or acting on patients after a stroke (secondary prevention) to prevent stroke recurrence and the progression of brain changes associated with cognitive impairment are mandatory therapeutic strategies.

Cerebrolysin in Vascular Dementia: Improvement of Clinical Outcome in a Randomized, Double-Blind, Placebo-Controlled Multicenter Trial

No drug to treat vascular dementia (VaD) has yet been approved by the American or European authorities, leaving a large population of patients without effective therapy. Cerebrolysin has a long record of safety and might be efficacious in this condition. We conducted a large, multicenter, double-blind, placebo-controlled study in 242 patients meeting the criteria for VaD. The primary endpoint was the combined outcome of cognition (based on Alzheimer's Disease Assessment Scale Cognitive Subpart, Extended Version [ADAS-cog+] score) and overall clinical functioning (based on Clinician's Interview-Based Impression of Change plus Caregiver Input [CIBIC+] score) assessed after 24 weeks of treatment. Intravenous Cerebrolysin 20 mL was administered once daily over the course of 2 treatment cycles as add-on therapy to basic treatment with acetylsalicylic acid. The addition of Cerebrolysin was associated with significant improvement in both primary parameters. At week 24, ADAS-cog+ score improved by 10.6 points in the Cerebrolysin group, compared with 4.4 points in the placebo group (least squares mean difference, -6.17; P < .0001 vs placebo). CIBIC+ showed a mean improvement of 2.84 in the treatment arm and 3.68 in the placebo arm, a treatment difference of 0.84 (P < .0001 vs placebo). These findings were confirmed by responder analyses demonstrating higher rates in the Cerebrolysin group (ADAS-cog+ improvement of ≥4 points from baseline, 82.1% vs 52.2%; CIBIC+ score of <4 at week 24, 75.3% vs 37.4%; combined response in ADAS-cog+ and CIBIC+, 67.5% vs 27.0%). For Cerebrolysin, the odds ratio for achieving a favorable CIBIC+ response was 5.08 (P < .05), and that for achieving a favorable combined response was 5.63 (P < .05). Our data indicate that the addition of Cerebrolysin significantly improved clinical outcome, and that the benefits persisted for at least 24 weeks. Cerebrolysin was safe and well tolerated.

Does diabetes mellitus alter the onset and clinical course of vascular dementia?

Background: Vascular dementia (VaD) is the second most common dementing illness. Multiple risk factors are associated with VaD, but the individual contribution of each to disease onset and progression is unclear. We examined the relationship between diabetes mellitus type 2 (DM) and the clinical variables of VaD. Methods: Data from 593 patients evaluated between June, 2003 and June, 2008 for cognitive impairment were prospectively entered into a database. We retrospectively reviewed the charts of 63 patients who fit the NINDSAIREN criteria for VaD. The patients were divided into those with DM (VaDDM, n = 29) and those without DM(VaD, n = 34). The groups were compared with regard to multiple variables. Results: Patients with DM had a significantly earlier onset of VaD (71.9 ± 6.54 vs. 77.2 ± 6.03,p < 0.001), a faster rate of decline per year on the mini mental state examination (MMSE; 3.60 ± 1.82 vs. 2.54 ± 1.60 points, p = 0.02), and a greater prevalence of neuropsychiatric symptoms at the time of diagnosis (62% vs. 21%, p = 0.02). Conclusions: A history of premorbid DM was associated with an earlier onset and faster cognitive deterioration in VaD. Moreover, DM was associated with neuropsychiatric symptoms in patients with VaD. A larger study is needed to verify these associations. It will be important to investigate whether better glycemic control will mitigate the potential effects of DM on VaD.

Does Diabetes Mellitus Alter the Onset and Clinical Course of Vascular Dementia?

Background:Vascular dementia (VaD) is the second most common dementing illness. Multiple risk factors are associated with VaD, but the individual contribution of each to disease onset and progression is unclear. We examined the relationship between diabetes mellitus type 2 (DM) and the clinical variables of VaD.Methods:Data from 593 patients evaluated between June, 2003 and June, 2008 for cognitive impairment were prospectively entered into a database. We retrospectively reviewed the charts of 63 patients who fit the NINDSAIREN criteria for VaD. The patients were divided into those with DM (VaDDM, n = 29) and those without DM(VaD,n= 34). The groups were compared with regard to multiple variables.Results:Patients with DM had a significantly earlier onset of VaD (71.9 ± 6.54 vs. 77.2 ± 6.03,p&lt; 0.001), a faster rate of decline per year on the mini mental state examination (MMSE; 3.60 ± 1.82 vs. 2.54 ± 1.60 points,p= 0.02), and a greater prevalence of neuropsychiatric symptoms at the time of diagnosis (62% vs. 21%,p= 0.02).Conclusions:A history of premorbid DM was associated with an earlier onset and faster cognitive deterioration in VaD. Moreover, DM was associated with neuropsychiatric symptoms in patients with VaD. A larger study is needed to verify these associations. It will be important to investigate whether better glycemic control will mitigate the potential effects of DM on VaD.

The Pathology of “Vascular Dementia”: A Critical Update

The prevalence, morphology and pathogenesis of vascular dementia (VaD), recently termed vascular cognitive disorder (VCD), are a matter of discussion.VaD is suggested in 8-15% of cognitively impaired aged subjects. Its prevalence in autopsy series ranges from 0.03 to 58% (mean 8-15% in Western series, 22-35% in Japan). Neuropathology shows multifocal and/or diffuse lesions, ranging from lacunes and microinfarcts, often involving subcortical and strategically important brain areas (thalamus, frontobasal, limbic system), white matter lesions and hippocampal sclerosis to multi-infarct encephalopathy and diffuse post-ischemic lesions. They result from systemic, cardiac and local large and small vessel disease. Pathogenesis is multifactorial and pathophysiology affects neuronal networks involved in cognition, behavior, execution and memory. Vascular lesions often coexist with Alzheimer's disease (AD) and other pathologies. Minor vascular lesions hardly contribute to cognitive decline in full-blown AD, while both mild Alzheimer pathology and small vessel disease interact synergistically. AD pathology is less severe in the presence of vascular lesions. The lesion pattern in "pure" VaD/VCD) related to microangiopathies differs from that in "mixed dementia" (AD + vascular encephalopathy), often associated with large infarcts, suggesting different pathogenesis. Due to the heterogeneity of cerebrovascular pathology and its causative factors, no validated neuropathologic criteria for VaD are currently available, and a large variability across laboratories still exists in morphologic examination procedures and techniques. Further prospective clinico-pathologic studies are needed to validate diagnostic criteria for VaD and to clarify the impact of vascular lesions on cognitive impairment.

Comparability of the Clinical Diagnostic Criteria for Vascular Dementia: A Critical Review. Part I

Comparability of the Clinical Diagnostic Criteria for Vascular Dementia: A Critical Review. Part I