Probable Vascular Dementia Research Articles

Vascular disease burden in Indian subjects with vascular dementia.

Vascular disease factors like hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease contribute to the development of vascular dementia. As comorbidity of vascular disease factors in vascular dementia is common, we investigated the vascular disease burden in subjects with vascular dementia. To investigate the vascular disease burden due to four vascular disease factors: hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease in Indian subjects with vascular dementia. In this study, 159 subjects with probable vascular dementia (as per NINDS-AIREN criteria) attending the memory clinic at a tertiary care hospital were assessed for the presence of hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease using standardised operational definitions and for severity of dementia on the Clinical Dementia Rating (CDR) scale. The data obtained was subjected to appropriate statistical analysis. Dyslipidaemia (79.25 per cent) was the most common vascular disease factor followed by hypertension (73.58 per cent), ischaemic heart disease (58.49 per cent), and diabetes mellitus (40.80 per cent). Most subjects (81.1 per cent) had two or more vascular disease factors. Subjects with more severe dementia had more vascular disease factors (sig 0.001). People with moderate to severe dementia have a significantly higher vascular disease burden; therefore, higher vascular disease burden may be considered as a poor prognostic marker in vascular dementia. Subjects with vascular dementia and their caregivers must manage cognitive impairment and ADL alongside managing serious comorbid vascular diseases that may worsen the dementia.

Overdiagnosing Vascular Dementia using Structural Brain Imaging for Dementia Work-Up.

Hypothesizing that non-significant cerebrovascular lesions on structural brain imaging lead to overdiagnosis of a vascular etiology of dementia as compared to autopsy-confirmed diagnosis, we set up a study including 71 patients with autopsy-confirmed diagnoses. Forty-two patients in the population (59%) appeared to have definite Alzheimer's disease (AD), whereas 29 (41%) had a non-AD dementia form. The panel clinically diagnosed possible or probable vascular dementia (VaD) in 27 (38%) patients, whereas only five (19%) patients (p = 0.017) had an autopsy-confirmed diagnosis of VaD. Patients with vascular lesions on structural brain imaging were often misdiagnosed as possible or probable VaD as compared to autopsy-confirmed diagnosis.

PROFILES OF ICF DISABILITY IN ALZHEIMER AND VASCULAR DEMENTIA

Backgrounds: The International Classification of Functioning, Disability and Health (ICF) is a suitable tool to standardize the status of health and disability. A previous study, carried out on 546 subjects included in the database ANASTE (National Association of Nursing Home for Third Age) Calabria, showed that 78.43% of the patients suffered from cognitive impairment whereas 52% had a severe degree of dementia. 65% of them was suffering from Alzheimer’s Disease (AD), whereas 23% from vascular dementia (VD). Objectives: Aim of this study was to analyse the prevalence of functional impairments, activity limitations and participation restrictions of patients affected by AD and VD. Design: Observational descriptive study. Setting: Nursing Homes ANASTE Calabria. Partecipants: 10 patients with probable AD (ADPr) and 10 patients affected by probable VD (VDPr). Measurements: All patients were underwent multidimensional geriatric assessment. The profiles of disability ICF, were expressed in terms of Capacity and Performance, and coded according to mild, medium, severe and complete disability. Environmental factors were skilled in facilitator or no facilitator. Results: The patients with ADPr displayed a severe impairment of functional status, and advanced clinical stage requiring higher care burden compared with VDPr patients. The ICF assessment showed that the global and specific Mental Functions, Communication and Interpersonal Relationships were more reduced in patients with ADPr respect those with VDPr. Conclusions: The identification of a ICF checklist of various forms of dementia, might provides a more detailed description of the profiles of disability and improving therapeutic, rehabilitative interventions and psico-social care.

Clinicoradiological comparison between vascular parkinsonism and Parkinson’s disease

ObjectiveTo compare the clinical and radiological features of vascular parkinsonism (VP) and Parkinson’s disease (PD).MethodsCross-sectional study where 15 patients with VP (8 (53.3%) men; aged 75.7±10.4 years) and 30 patients...

Younger age of dementia diagnosis in a Hispanic population in southern California

Prior studies of US Hispanics, largely performed on the East Coast, have found a younger age of dementia onset than in White non-Hispanics. We performed a cross-sectional study to examine clinical and sociodemographic variables associated with age of dementia diagnosis in older Hispanics and White, non-Hispanics in southern California. Two hundred ninety (110 Hispanic and 180 White non-Hispanic) community dwelling, cognitively symptomatic subjects, aged 50 years and older, were assessed and diagnosed with probable Alzheimer's disease or probable vascular dementia. Apolipoprotein E (APOE) genotype was assessed in a subset of cases. Analysis of variance and multiple stepwise linear regression were used to assess main effects and interactions of ethnicity with dementia severity (indexed by mini mental state examination scores) and other sociodemographic and clinical variables on age of dementia diagnosis. Hispanics were younger by an average of 4 years at the time of diagnosis, regardless of dementia subtype, despite a similar prevalence of the APOE ε4 genotype. The earlier age at diagnosis for Hispanics was not explained by gender, dementia severity, years of education, history of hypercholesterolemia, hypertension, or diabetes. Only ethnicity was significantly associated with age of onset. These findings confirm that US Hispanics living in the southwestern USA tend to be younger at the time of dementia diagnosis than their White non-Hispanic counterparts. As this is not explained by the presence of the APOE ε4 genotype, further studies should explore other cultural, medical, or genetic risk factors influencing the age of dementia onset in this population.

Vascular parkinsonism: a case series of 17 patients

To report the clinical and neuroimaging findings in a case series of vascular parkinsonism (VP). Seventeen patients with VP were evaluated with motor, cognitive, and neuroimaging standardized tests and scales. All patients had arterial hypertension. Ten patients were male and the mean age of the whole sample was 75.8±10.1 years. The mean age of parkinsonism onset was 72.2±10.0 years. Common clinical features were urinary incontinence (88.2%), lower limb parkinsonism with freezing of gait and falls (82.3%), and pyramidal signs (76.4%). The mean Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr scores were 72.5±21.6 points and 3.3±0.9 points, respectively. Sixteen (94.1%) patients had freezing of gait and executive dysfunction. Twelve (70.5%) patients had probable vascular dementia. The mean dose of levodopa was 530.9 mg/day. Unresponsiveness to the drug was confirmed by a 6.9 mean point reduction in the UPDRS score after the "practically defined off" test. This series provides a profile of VP with predominant lower-limb involvement, freezing of gait and falls, pyramidal signs, executive dysfunction, concomitant vascular dementia, and poor levodopa response.

Differences in rate of functional decline across three dementia types

BackgroundThe purpose of this study was to estimate differences in rates of functional decline in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and vascular dementia (VaD) and whether differences vary by age or sex. MethodsData came from 32 U.S. Alzheimer's Disease Centers. The cohort of participants (n = 5848) were ≥60 years of age and had clinical dementia with a primary etiologic diagnosis of probable AD, DLB, or probable VaD; a Clinical Dementia Rating-Sum of Boxes score <16; and a duration of symptoms ≤10 years. Dementia diagnoses were assigned using standard criteria. Annual mean rate of change of the Functional Activities Questionnaire (FAQ) score was modeled using multiple linear regression with generalized estimating equations adjusted for demographics, comorbidities, years since onset, and cognitive status (mean follow-up = 2.0 years). ResultsFAQ declined more slowly over time in those with VaD compared with AD (difference in mean annual rate of change: −0.91; 95% confidence interval [CI]: −1.68, −0.14). VaD participants also declined at a slower rate than DLB participants, but this difference was not statistically significant (−0.61; 95% CI: −1.45, 0.24). There was no significant difference between DLB and AD. Within each group, rate of decline was more rapid for the youngest participants. ConclusionsIn this sample, findings suggested that VaD patients declined in their functional abilities at a slower rate compared with AD patients and that there were no significant differences in rate of functional decline between patients with DLB compared with those with either AD or VaD. These results may provide guidance to clinicians about average expected rates of functional decline in three common dementia types.

Late-Life Depression, Mild Cognitive Impairment, and Dementia

To evaluate the association of late-life depression with mild cognitive impairment (MCI) and dementia in a multiethnic community cohort. A cohort study was conducted in Northern Manhattan, New York, New York. A total of 2160 community-dwelling Medicare recipients aged 65 years or older were included in the study. Depression was assessed using the 10-item version of the Center for Epidemiological Studies Depression scale (CES-D) and defined by a CES-D score of 4 or more. We used logistic regression for cross-sectional association analyses and proportional hazards regression for longitudinal analyses. Mild cognitive impairment dementia, and progression from MCI to dementia were the main outcome measures. We also used subcategories of MCI (amnestic and nonamnestic), and dementia (probable Alzheimer disease and vascular dementia, including possible Alzheimer disease with stroke). Baseline depression was associated with prevalent MCI (odds ratio, 1.4; 95% CI, 1.1-1.9) and dementia (2.2; 1.6-3.1). Baseline depression was associated with an increased risk of incident dementia (hazard ratio [HR], 1.7; 95% CI, 1.2-2.3) but not with incident MCI (0.9; 0.7-1.2). Persons with MCI and coexisting depression at baseline had a higher risk of progression to dementia (HR, 2.0; 95% CI, 1.2-3.4), especially vascular dementia (4.3; 1.1-17.0), but not Alzheimer disease (1.9; 1.0-3.6). The association of depression with prevalent MCI and with progression from MCI to dementia, but not with incident MCI, suggests that depression accompanies cognitive impairment but does not precede it.

Internet-Based Screening for Dementia Risk

The Dementia Risk Assessment (DRA) is an online tool consisting of questions about known risk factors for dementia, a novel verbal memory test, and an informant report of cognitive decline. Its primary goal is to educate the public about dementia risk factors and encourage clinical evaluation where appropriate. In Study 1, more than 3,000 anonymous persons over age 50 completed the DRA about themselves; 1,000 people also completed proxy reports about another person. Advanced age, lower education, male sex, complaints of severe memory impairment, and histories of cerebrovascular disease, Parkinson's disease, and brain tumor all contributed significantly to poor memory performance. A high correlation was obtained between proxy-reported decline and actual memory test performance. In Study 2, 52 persons seeking first-time evaluation at dementia clinics completed the DRA prior to their visits. Their responses (and those of their proxy informants) were compared to the results of independent evaluation by geriatric neuropsychiatrists. The 30 patients found to meet criteria for probable Alzheimer's disease, vascular dementia, or frontotemporal dementia differed on the DRA from the 22 patients without dementia (most other neuropsychiatric conditions). Scoring below criterion on the DRA's memory test had moderately high predictive validity for clinically diagnosed dementia. Although additional studies of larger clinical samples are needed, the DRA holds promise for wide-scale screening for dementia risk.

The profile of behavioral and psychological symptoms in vascular cognitive impairment with and without dementia

Objective:The objective of this study was to compare the occurrence and severity of behavioral and psychological symptoms of dementia (BPSD) between vascular dementia (VaD) and vascular cognitive impairment-no dementia (VCI-ND).Materials and Methods:Consecutive patients presenting with cognitive impairment at least 3 months after an ischemic stroke and with a Hachinski Ischemic Score ≥4 were included. VaD was diagnosed as per National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria for probable VaD and VCI-ND on the lines of the Canadian study of health and aging. The severity of cognitive impairment and the behavioral/psychological symptoms were studied by means of the clinical dementia rating scale and the neuropsychiatric inventory (NPI) respectively.Results:All patients with VaD and 89% of those with VCI-ND had at least one BPSD. The mean no. of symptoms per patient and the total NPI scores were higher in VaD than in VCI-ND. Apathy and night-time behavior disturbances were significantly more common and severe in VaD.Conclusions:BPSD are very common both in VCI-ND and in VaD. The profile of BPSD is similar in both groups, albeit more severe in VaD. The net burden of BPSD is higher in VaD as compared to VCI-ND.

Vascular Cognitive Impairment (VCI) after non-embolic ischemic stroke during a 12-month follow-up in Brazil.

VCI represents a spectrum of cognitive impairments associated with stroke, vascular brain injury, or subclinical disease ranging from the least to most severe manifestations. Few studies are available on the prevalence of post-stroke VCI and none have been conducted in Brazil.ObjectiveTo determine the prevalence rates of VCI and associated risk factors in a sample of ischemic stroke patients.MethodsWe evaluated 172 patients with ischemic stroke for cognitive impairment one year after ictus.ResultsPatients comprised 81 women (47.1%) and had a mean age of 67.77 (7.86) years, schooling of 3.52 (2.99) years, and MMSE score of 24.94 (3.59) points. After cognitive evaluation, 4.6% were diagnosed as CIND (cognitive impairment no dementia) and 12.2% had a diagnosis of dementia (probable vascular dementia in 20 patients and one subject with cerebrovascular disease and Alzheimer's disease).ConclusionThe prevalence of dementia was lower than previous reports but our sample had a lower age than others, while a 12 month-period of follow-up prevented interference from associated neurodegenerative disorders.

Prevention of Vascular Cognitive Impairment

Dementia has become a pressing health issue, with numbers steadily increasing. Vascular injury is the second most common cause of dementia after Alzheimer disease (AD) and a defining feature of vascular cognitive impairment (VCI), which encompasses the full range from vascular dementia (VaD) to mild cognitive impairment of vascular origin.1,2 There are various manifestations of vascular brain injury, including silent or covert brain infarcts, white matter lesions, and clinically overt strokes, all of which may contribute to cognitive decline. Cerebral small vessel disease has been recognized as the most common etiology of VCI, but there are multiple vascular causes and mechanisms that share major risk factors and may run in parallel. Adding to this complexity, vascular pathology frequently coincides with neurodegenerative pathology and disentangling the contribution of individual pathologies to cognitive decline is notoriously difficult even with advanced diagnostic tools. This is reflected by current classification schemes, which distinguish between probable and possible VaD and probable and possible vascular mild cognitive impairment.2 However, there have been various sets of diagnostic criteria in the past, which must be kept in mind when interpreting the results from epidemiological studies and randomized controlled trials (RCT). Regardless of these methodological challenges, vascular brain injury represents an increasingly recognized target for prevention of cognitive decline and dementia. There are various modifiable factors that have been associated with VCI or VaD in clinical and epidemiological studies (Figure 1), although in many cases the causal relationships are not fully established and evidence for a preventive effect of strategies to control these factors is mostly weak. Figure 1. Risk factors for vascular dementia (VaD), Alzheimer disease (AD), unspecified dementia, and cognitive impairment. Findings are derived from epidemiological studies. Relevant references are detailed in Supplementary Table I. VaD and AD share many risk factors, although the level …

Clock drawing testing and diffusion tensor imaging among vascular dementia versus Alzheimer's disease

PurposeTo assess the clock drawing testing (CDT) and diffusion tensor magnetic resonance imaging (DT-MRI) differences between probable Alzheimer's dementia (AD) and vascular dementia (VaD) and the CDT correlation with the DT-MRI. Subjects and methodsElderly patients presenting at the Geriatric outpatient clinic-Ain Shams University Hospitals, Egypt over a period of 6 months were recruited for the study. Tools of assessment including activities of daily living, geriatric depression scale-15 items, Mini-mental status examination, and Clock drawing test using Shulman et al. scoring system were applied to all participants. Diagnosis of dementia and its subtypes was confirmed using DSM-IV criteria. From the assessed subjects, thirty participants; ten cases of probable AD, ten cases of VaD and ten controls, were randomly chosen for assessment using DT-MRI, where apparent diffusion coefficient (ADC), and fractional anisotropy (FA), were evaluated in 15 regions of interest in the cerebral hemispheres. ResultsVaD cases showed significantly worse performance in CDT than AD cases with more prevalence of spacing errors among them. CDT had significant correlation with age, MMSE and ADL. Dementia was associated with increased ADC and decreased FA in DT-MRI. VaD had lower FA than AD. CDT was significantly correlated with white matter integrity of several areas on DT-MRI. ConclusionCDT differs among VaD and AD with a range of radiological correlations. DT-MRI is a sensitive and discriminative technique for evaluation of patients with dementia including probable AD and VaD. Larger studies are needed for establishing reference ranges.

Neuropsychological performance in patients with subcortical stroke

Vascular cognitive impairment (VCI) is characterized by cognitive compromise predominantly of executive dysfunction. To assess cognitive functions in VCI, focusing on executive functions, to observe functional losses in relation to activities of daily living (ADLs) and to detect early symptoms prior to the onset of dementia. We evaluated healthy subjects matched for gender, education and age to patients with diagnosis of subcortical vascular disease who had a stroke classified into three groups: 1) vascular lesions and no impairment; 2) vascular cognitive impairment with no dementia (VCIND); 3) vascular dementia (VaD). The performance on neuropsychological tests differed among groups, worsening with increased impairment level. The probable VaD group demonstrated impaired performance in memory, processing speed and verbal production, while the VCIND group showed attention deficits. Impairment in executive functions and difficulties in ADLs allow us to differentiate levels of impairment in groups of subcortical vascular disease.

Letter by Rodríguez-García and Rodríguez-García Regarding Article, “Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association”

HomeStrokeVol. 42, No. 11Letter by Rodríguez-García and Rodríguez-García Regarding Article, “Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Rodríguez-García and Rodríguez-García Regarding Article, “Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association” Pedro Luis Rodríguez-García, MD and Damaris Rodríguez-García, MD Pedro Luis Rodríguez-GarcíaPedro Luis Rodríguez-García Search for more papers by this author and Damaris Rodríguez-GarcíaDamaris Rodríguez-García Search for more papers by this author Originally published22 Sep 2011https://doi.org/10.1161/STROKEAHA.111.634279Stroke. 2011;42:e584is corrected byCorrectionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:Recently Gorelick et al published an interesting overview of the evidence on vascular contributions to cognitive impairment and dementia.1 This statement provides some outstanding aspects for practical classification of vascular cognitive impairment (VCI). First, the recent published advances in dementia and mild cognitive impairment definitions were summarized.2,3 Second, the guideline proposes a different perspective for some terms used for classifying certainty of VCI diagnosis (eg, probable for the most “pure” forms of vascular dementia and possible when the certainty of the diagnosis is diminished or exist a “mixed” process).1 However, in contrast with some classical criteria,4,5 the definitive level is currently not specified.Third, the following criteria description (Table 2) should be interpreted with caution: (1) For possible VCI, there is no clear relationship (temporal, severity, or cognitive pattern) between the vascular disease (eg, silent infarcts, subcortical small-vessel disease) and the cognitive impairment.1 However, no definitions are expressed for temporal, severity, and cognitive pattern relationship. Is temporal relation related to the 3-month poststroke cutoff? Is severity defined according classical criteria published? Is cognitive pattern a relationship criterion considered without cerebral localization diagnosis? Which singular or specific cognitive pattern can be applied for the heterogeneous forms of vascular dementia? (2) For possible VCI, there is cognitive impairment and imaging evidence of cerebrovascular disease, but information is insufficient for the diagnosis of vascular dementia (eg, clinical symptoms suggest the presence of vascular disease, but no CT/MRI studies are available).1 Then, is imaging evidence of cerebrovascular disease (CT/MRI) available? (3) Possible VCI is stated when severity of aphasia precludes proper cognitive assessment. However, patients with documented evidence of normal cognitive function (eg, annual cognitive evaluations) before the clinical event that caused aphasia could be classified as having probable vascular dementia.1 What are the foundations for the previously diagnosis of cognitive impairment if aphasia precludes proper assessment? Which precise criteria about aphasia are obviated if the word could is used? (4) There is no history of gradually progressive cognitive deficits before or after the stroke that suggests the presence of a nonvascular neurodegenerative disorder for probable VCI.1 However, some types of undoubtedly vascular dementia could start and develop in an insidious fashion without any clinically apparent stroke. Is it appropriate to consider a possible VCI when cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy is diagnosed by progressive cognitive changes, typical findings on MRI, and mutations in the Notch 3 gene?In conclusion, until now, several groups of criteria have been proposed to decrease subjectivity and disagreement in the diagnosis of VCI. Unfortunately, none of these diagnostic criteria have satisfactorily consistency with regard to the onset, evolution, cognitive profiles, imaging evidence, and pathological markers. There is a need for agreement on criteria for the diagnosis of VCI as well as subtypes that would take into consideration the diverse mechanisms of the cerebrovascular disease.6 These criteria would be flexible enough to be used by healthcare providers as well as specialized investigators.Pedro Luis Rodríguez-García, MD Neurology Service E. Guevara Hospital Las Tunas, CubaDamaris Rodríguez-García, MD Radiology Service L. Iñiguez Hospital Holguín, CubaDisclosuresNone.FootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).

Influence of Education on Subcortical Hyperintensities and Global Cognitive Status in Vascular Dementia

Subcortical hyperintensities (SH) on neuroimaging are a prominent feature of vascular dementia (VaD) and SH severity correlates with cognitive impairment in this population. Previous studies demonstrated that SH burden accounts for a degree of the cognitive burden among VaD patients, although it remains unclear if individual factors such as cognitive reserve influence cognitive status in VaD. To address this issue, we examined 36 individuals diagnosed with probable VaD (age = 77.56; education = 12). All individuals underwent MMSE evaluations and MRI brain scans. We predicted that individuals with higher educational attainment would exhibit less cognitive difficulty despite similar levels of SH volume, compared to individuals with less educational attainment. A regression analysis revealed that greater SH volume was associated with lower scores on the MMSE. Additionally, education moderated the relationship between SH volume and MMSE score, demonstrating that individuals with higher education had higher scores on the MMSE despite similar degrees of SH burden. These results suggest that educational attainment buffers the deleterious effects of SH burden on cognitive status among VaD patients.

Persistence of the effects of Cerebrolysin on cognition and qEEG slowing in vascular dementia patients: Results of a 3-month extension study

The maintenance of the effects of Cerebrolysin, a peptidergic compound with neurotrophic activity, on cognitive performance and qEEG activity was investigated through a 12-week, open-label extension of a 4-week, randomised, placebo-controlled pilot study. Thirty-three out of 41 patients with mild-to-moderate severe probable vascular dementia (VaD) according to NINDS-AIREN participating in the double-blind phase of the study were also assessed at the follow-up visit at week 16. Patients received i.v. infusions of Cerebrolysin (10 or 30 mL) or placebo (saline) 5 days/week for 4 weeks. Neuropsychological evaluations and qEEG recordings were done at baseline, week 4 and week 16. The mean change in score from baseline in the ADAS-cog+ and the slow-to-fast qEEG power ratio (PR), used as an index of qEEG slowing, were the two primary endpoints. Correlations between changes in cognition and qEEG induced by the treatment were also assessed. At the week 16 follow-up visit, Cerebrolysin improved (p < 0.05) cognitive performance at the 10-mL and 30-mL doses and reduced qEEG slowing significantly (p < 0.05) at the 30-mL dose with respect to the placebo. In addition, a significant (p < 0.05) positive correlation between the change from the baseline qEEG PR and ADAS-cog+ variables was observed at week 16. These results indicate a persistence of the beneficial effects of Cerebrolysin on cognition and qEEG activity in VaD patients for at least 12 weeks after treatment cessation, and they suggest the potential utility of qEEG parameters as biomarkers for VaD clinical trials.

Randomized, Placebo-Controlled, Clinical Trial of Donepezil in Vascular Dementia

We sought to assess the efficacy and safety of donepezil in patients with vascular dementia (VaD) fulfilling National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria. This international, multicenter, 24-week trial was conducted from March 2003 to August 2005. Patients (N=974; mean age, 73.0 years) with probable or possible VaD were randomized 2:1 to receive donepezil 5 mg/d or placebo. Coprimary outcome measures were scores on the Vascular-Alzheimer Disease Assessment Scale-Cognitive Subscale and Clinician's Interview-Based Impression of Change, plus carer interview. Analyses were performed for the intent-to-treat population with the last-observation-carried-forward method. Compared with placebo, donepezil-treated patients showed significant improvement from baseline to end point on the Vascular-Alzheimer Disease Assessment Scale-Cognitive Subscale (least-squares mean difference, -1.156; 95% CI, -1.98 to -0.33; P<0.01) but not on the Clinician's Interview-Based Impression of Change, plus carer interview. Patients with hippocampal atrophy who were treated with donepezil demonstrated stable cognition versus a decline in the placebo-treated group; in those without atrophy, cognition improved with donepezil versus relative stability with placebo. Results on secondary efficacy measures were inconsistent. The incidence of adverse events was similar across groups. Eleven deaths occurred in the donepezil group (1.7%), similar to rates previously reported for donepezil trials in VaD, whereas no deaths occurred in the placebo group. Patients treated with donepezil 5 mg/d demonstrated significant improvement in cognitive, but not global, function. Donepezil was relatively well tolerated; adverse events were consistent with current labeling. Mortality in the placebo group was unexpectedly low. The differential treatment response of VaD patients by hippocampal size suggests that hippocampal imaging warrants further investigation for understanding VaD.

Midlife Use of Written Japanese and Protection From Late Life Dementia

The cognitive reserve hypothesis would predict that use of written Japanese should confer protection against dementia because of the complexity of its ideograms compared with written English. We sought to test this hypothesis in analyses from a longitudinal study of Japanese-American men. Participants were second-generation Japanese-American men (Nisei) on the island of Oahu, Hawaii, who were seen in 1965 and in subsequent examinations to detect dementia beginning in 1991-1993. Use of spoken and written Japanese was self-reported in 1965 (Analyses 1 and 2), and midlife use of written Japanese and written English was self-reported in 1994-1996 (Analysis 3). We analyzed prevalent dementia outcomes in 1991-1993 (Analysis 1, n = 3139) using logistic regression, and incident dementia outcomes in 1994-2002 (Analysis 2, n = 2299) and in 1997-2002 (Analysis 3, n = 1655) using Cox proportional hazards regression. Dementia outcomes included all-cause dementia, probable and possible Alzheimer disease, and probable vascular dementia. We adjusted models for probable and possible confounders. Participants who reported proficiency with written Japanese were older and had lower incomes. For Analysis 1, there were 154 prevalent cases of dementia, 74 of Alzheimer disease, and 43 of vascular dementia; for Analysis 2, 236 incident cases of dementia, 138 of Alzheimer disease, and 45 of vascular dementia; and for Analysis 3, 125 incident cases of dementia, 80 of Alzheimer disease, and 20 of vascular dementia. There was no relationship in adjusted models between self-reported proficiency with written Japanese and any dementia outcomes. Proficiency with written Japanese does not appear to be protective for dementia.

The long‐term efficacy and tolerability of donepezil in patients with vascular dementia

To determine the long-term tolerability and efficacy of donepezil in patients with vascular dementia (VaD). International, multicentre, open-label, 30-week extension study of two 24-week, randomised, double-blind, placebo-controlled studies. Participants were ambulatory adults (59% female; mean age, 74.7 +/- 0.3) with a diagnosis of possible or probable VaD and without a diagnosis of Alzheimer's disease, who were medically stable and had completed one of two double-blind studies. All patients received donepezil 5 mg/day for the first 6 weeks, then 10 mg/day (clinician approval required). Assessments were performed at week 6 and every 12 weeks thereafter. The main outcome measure was the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-cog). Safety/tolerability measures included adverse events (AEs) and physical and laboratory evaluations. Of 1219 eligible patients, 885 (72.6%) were enrolled, of which 707 (79.9%) completed the study; 127 (14.4%) patients discontinued due to AEs. A mean reduction (0.6-1.15 points) from double-blind study baseline score to week 54 (end of open-label study) on the ADAS-cog was observed for patients who received donepezil continuously for 54 weeks. ADAS-cog scores remained stable in the group that initiated donepezil treatment during the extension study. Most common donepezil-related AEs were nausea (occurring in 5.3%) and diarrhoea (8.8%); no unexpected AEs attributable to donepezil occurred. These data suggest that donepezil improves cognition for up to 54 weeks in patients with VaD. Patients initiating donepezil in this extension study did not perform as well on the primary outcome measure as those initiating donepezil in the double-blind study.