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Biomedical subjects

Gustavo C Román

Publications and source records attributed to Gustavo C Román.

At least 19 recordsLinked to original sources
PubMed2006

Socio-demographic variation of dementia subtypes in china: Methodology and results of a prevalence study in Beijing, Chengdu, Shanghai, and Xian.

OBJECTIVE: To characterize sociodemographic variations in the prevalence of AD and VaD in China. METHODS: Data were collected in a 1997-1998, cross-sectional, door-to-door prevalence survey of 34,807 community residents ages > or =55 years in Beijing, Shanghai, Chengdu and Xian. Initial diagnoses of AD and VaD were assessed by clinicians using standardized protocols, according to the NINCDS-ADRDA and NINDS-AIREN criteria; diagnoses were confirmed after 6 months by repeating neuropsychological evaluations. Prevalence odds ratios were estimated in logistic models adjusting for survey design, age, and other sociodemographic factors. RESULTS: We identified 732 prevalent cases of AD and 295 cases of VaD. Adjusting for all sociodemographic factors concurrently, prevalence odds of AD and VaD were higher in northern versus southern China. Age trends for AD appeared different in western and eastern China. AD also showed an age-adjusted elevation among women and, in the fully adjusted model, a gender education interaction indicating a female preponderance in the highest education group. North-south variation for VaD was age-dependent. In the fully adjusted model, for AD, widowed had significantly higher prevalence odds; for VaD, widowed persons and minorities had significantly lower prevalence odds; professionals had statistically significant and borderline lower prevalence odds for both VaD and AD; sales-service occupations had significantly lower odds for AD only. CONCLUSION: We observed variations in prevalence for AD and VaD in different regions and demographic groups in China that persisted after controlling for potential confounding factors. Sociodemographic factors are probable surrogates for conditions such as lifestyle, environment, comorbidities, and life expectancy.

Age Factors↗
PubMed2005

Vascular dementia prevention: a risk factor analysis.

Brain injury from ischemic or hemorrhagic cerebrovascular disease (CVD) produces decline in cognitive functions and vascular dementia (VaD). Likewise, CVD may cause VaD from hypoperfusion of susceptible brain areas. CVD may also worsen degenerative dementias such as Alzheimer's disease. Significant advances have been made in the identification and control of risk factors for stroke and cardiovascular disease. The main risk factors for VaD include age, hypertension and absence of antihypertensive medication, diabetes, cigarette smoking, history of cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, and sleep apnea. Recently identified risk factors include chronic infection and elevation of C-reactive protein, particularly in patients with diabetes. Evidence from controlled clinical trials strongly suggests that control of vascular risk factors, in particular hypertension, could prevent the development of dementia.

Aged↗
PubMed2005

Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia.

Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.

Alzheimer Disease↗
PubMed2005

Donepezil in vascular dementia: combined analysis of two large-scale clinical trials.

BACKGROUND AND OBJECTIVE: There are currently no drugs approved to treat vascular dementia (VaD). The objective of this study was to determine if treatment with donepezil, an acetylcholinesterase inhibitor, may provide benefit for VaD patients. METHODS: Combined analysis of 2 identical randomized, double-blind, placebo-controlled, 24-week studies involving 1,219 patients enrolled at 109 investigational sites in the USA, Europe, Canada and Australia. Patients were randomized to receive donepezil 5 mg/day (n = 406) or 10 mg/day (after brief titration; n = 421) or placebo (n = 392). Patients were assessed on cognition [Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE)], global function [Clinician's Interview-Based Impression of Change plus (CIBIC-plus), Clinical Dementia Rating-Sum of the Boxes (CDR-SB)] and function [Alzheimer's Disease Functional Assessment and Change Scale (ADFACS); instrumental activities of daily living (ADFACS-IADL)]. RESULTS: Both donepezil groups showed significant improvements in cognition compared with placebo (ADAS-cog, MMSE, p < 0.01). Significant global function benefits were seen on the CIBIC-plus in the 5 mg/day group (placebo vs. 5 mg/day, p < 0.001; vs. 10 mg/day, p = 0.006) and on the CDR-SB in the 10 mg/day group (placebo vs. 5 mg/day, p = 0.09; vs. 10 mg/day, p < 0.01). Significant functional benefits were also seen (ADFACS, placebo vs. 5 mg/day, p = 0.08; vs. 10 mg/day, p = 0.02; ADFACS-IADL, p < 0.05 for both donepezil groups). Donepezil was well tolerated, with low withdrawal rates due to adverse events. CONCLUSIONS: This combined analysis of the largest trial on VaD to date showed that donepezil-treated patients had significant benefits in cognition, global function and ability to perform IADL. Based on these findings and reported tolerability, donepezil should be considered as an important therapeutic element in the overall management of patients with VaD.

Activities of Daily Living↗
PubMed2005

Dementia subtypes in China: prevalence in Beijing, Xian, Shanghai, and Chengdu.

BACKGROUND: Prevalences of Alzheimer disease (AD) and vascular dementia (VaD) in China reportedly differ from those in Western countries. OBJECTIVE: To estimate prevalence of AD and VaD in 4 regions of China. DESIGN: Cross-sectional, population-based prevalence survey with a stratified, multistage cluster sampling design. SETTING: Rural (n = 99) and urbanized (n = 71) communities of Beijing, Xian, Shanghai, and Chengdu. PARTICIPANTS: A sample of 34 807 community residents (94% of those eligible) 55 years or older. MAIN OUTCOME MEASURES: Participants were screened with the Chinese Mini-Mental State Examination. Those who screened positive (n = 3950) underwent a standardized diagnostic workup. Screening sensitivity was assessed in a 3.3% random sample (n = 1008 of the 30 857 who passed the screening). Diagnoses of AD and VaD were made according to National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer Disease and Related Disorders Association and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria, respectively. Final diagnoses were made after a 6-month confirmation interval. RESULTS: We identified 732 AD cases and 295 VaD cases. Prevalence in persons 65 years or older was 3.5% (95% confidence interval, 3.0%-3.9%) for AD and 1.1% (95% confidence interval, 0.9%-1.1%) for VaD. After post hoc correction for negative screening errors, prevalence increased to 4.8% for AD and remained at 1.1% for VaD. CONCLUSION: Prevalence of dementia subtypes in China is comparable with that in Western countries.

Aged↗
PubMed2005

Cholinergic dysfunction in vascular dementia.

Vascular dementia (VaD) is the second most common type of dementia in the elderly after Alzheimer's disease (AD). Evidence is presented indicating the occurrence of cholinergic dysfunction in VaD, independent from AD. Controlled clinical trials of cholinesterase inhibitors (ChEIs) in VaD and in patients with AD plus cerebrovascular disease are reviewed. Compared with placebo, ChEI treatment improves cognition, behavior, and activities of daily living. Cholinergic deficits in patients with VaD may result from ischemia of basal forebrain cholinergic nuclei that are irrigated by penetrating arteries that are highly susceptible to arterial hypertension, or from ischemic lesions in basal ganglia or white matter that sever the extensive cholinergic cortical projections. Cholinergic stimulation produces increases in cortical cerebral blood flow that may be relevant to the therapeutic effect of ChEIs.

Acetylcholinesterase↗
PubMed2005

Rivastigmine for subcortical vascular dementia.

Rivastigmine is a second-generation cholinesterase inhibitor with selectivity for the CNS, with capacity to inhibit both acetylcholinesterase and butyrylcholinesterase. Rivastigmine is currently approved for the treatment of mild-to-moderate Alzheimer's disease. In addition to its effects on cognition and activities of daily living, rivastigmine appears to be useful in preventing and controlling behavioral and neuropsychiatric manifestations in Alzheimer's disease and dementia with Lewy bodies. This drug profile could be potentially useful in patients with subcortical vascular dementia who often present these symptoms. Small open-label studies of patients with subcortical vascular dementia showed that rivastigmine improved attention, executive function, apathy and other behavioral deficits. Rivastigmine appears to be a promising agent in vascular dementia but its effects remain to be established in double-blind, placebo-controlled clinical trials.

Alzheimer Disease↗
PubMed2004

Facts, myths, and controversies in vascular dementia.

Significant progress in the field of VaD resulted from publication of the NINIDS-AIREN Diagnostic Criteria for VaD (G.C. Roman, T.K. Tatemichi, T. Erkinjuntti, et al., Vascular dementia (VaD): diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43 (1993) 250-260). Epidemiological studies confirmed the importance of VaD as the second most common cause of dementia in the elderly, representing 15-20% of all cases of dementia. In Europe and North America, Alzheimer's disease (AD) predominates over VaD in a 2:1 ratio; in contrast, in Japan and China VaD accounts for almost 50% of all dementias. Case-control studies have identified risk factors for VaD including ageing, hypertension, diabetes mellitus, hyperlipidemia, recurrent stroke, cardiac disease, smoking, sleep apnea, and more recently, hyperhomocysteinemia, among others. Hypertension treatment may prevent VaD and AD. This finding has enormous importance from the Public Health viewpoint to decrease the future number of patients with dementia in the elderly. Along with advances in the field of VaD came a number of controversies and damaging misconceptions and myths. Myth no. 1--Vascular dementia is a non-entity: The false idea that VaD does not exist is particularly destructive because it creates the perspective that VaD is unworthy of study or research. A condition that either does not exist or represents only a minute proportion of all cases of dementia in the elderly, lacks public health relevance and becomes a low priority for research by funding agencies and industry. In fact, vascular brain lesions are the commonest and most important component of dementia in the elderly. Myth no. 2--Vascular dementia is so difficult to diagnose that only experts can recognize and identify it accurately: VaD does exist and the diagnosis of post-stroke VaD, in particular is straightforward. Most cases fulfill NINDS-AIREN criteria for probable VaD; i.e., (1) there is acute onset of dementia demonstrated by impairment of memory and two other cognitive domains, such as orientation, praxis or executive dysfunction; (2) relevant cerebrovascular lesions are demonstrated by neuroimaging; and (3) a temporal relation between stroke and cognitive loss is evident. In the donepezil trials on VaD, post-stroke dementia represented about 75% of the >1,200 patients enrolled. Myth no. 3--Improvement in clinical trials of cholinergics in VaD is due to underlying AD, not to the vascular lesions. Experimental, clinical and pathological evidence has demonstrated cholinesterase deficits in VaD (independently of any concomitant AD pathology), including low acetylcholine in cerebrospinal fluid, and reduced choline acetyltransferase (ChAT) in the brain.

Aged↗
PubMed2004

Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia.

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions. Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.

Aged↗
PubMed2004

Brain hypoperfusion: a critical factor in vascular dementia.

Subcortical ischemic vascular dementia is a relatively common form of dementia. Anatomical changes of ageing in the brain arteries predispose the elderly to the effects of hypotension. Depending on their circulatory pattern, particular regions of the brain are susceptible to ischemic hypoperfusive lesions. These regions include the periventricular white matter, basal ganglia, and hippocampus. Interruption of prefrontal-basal ganglia circuits important for cognition and memory may result from these lesions. Hypotension and hypoperfusion explain the high risk for the development of cognitive impairment and vascular dementia in older patients affected by orthostatic hypotension, congestive heart failure, as well as in those undergoing surgical procedures such as hip and knee replacement and coronary artery bypass graft (CABG). Recognition of the susceptibility of elderly subjects to cerebral lesions induced by hypoperfusion should result in appropriate preventive measures and better treatment.

Age Factors↗
PubMed2004

Donepezil: a clinical review of current and emerging indications.

This article reviews the piperidine derivative, donepezil hydrochloride (E2020, Aricept), a reversible central acetylcholinesterase inhibitor currently approved for treatment of mild-to-moderate Alzheimer's disease. Donepezil is well absorbed orally, unaffected by food or by time of administration; it reaches therapeutic levels in doses of 5-10 mg/day and peak plasma concentrations are obtained 3-4 h after oral administration. A single bedtime dose is recommended due to the long elimination half-life of the drug (70 h). Donepezil does not cause liver toxicity or significant drug interactions and is relatively well-tolerated. Initial side effects include nausea, vomiting, diarrhoea, insomnia, muscle cramps, fatigue, anorexia and syncope. Caution is advised in patients with bradycardia. Long-term use of donepezil in AD has been found to delay nursing-home placement and to result in caregiver respite. Donepezil also slows deterioration of cognition and global function in patients with moderate-to-severe AD, with improvement of abnormal behaviours. In addition to AD, donepezil demonstrates significant improvement in cognition, global function and activities of daily living in comparison with placebo-treated patients with vascular dementia and has potential therapeutic benefit for other neurological conditions.

Alzheimer Disease↗
PubMed2004

Myelopathy in Sjögren's syndrome: role of nonsteroidal immunosuppressants.

The incidence, aetiology and optimal treatment of CNS Sjögren's syndrome, including myelopathy associated with Sjögren's syndrome, are unknown at the present time. CNS Sjögren's syndrome is thought to be the result of an autoimmune vasculitis, but other mechanisms may be important. Spinal cord involvement in CNS Sjögren's syndrome may present as acute transverse myelitis, progressive myelitis, Brown-Séquard syndrome, neurogenic bladder or lower motor neurone disease. Optic nerve pathology frequently accompanies spinal cord involvement. Acute transverse myelitis has a high mortality and appears to be the most frequent form of spinal cord involvement in CNS Sjögren's syndrome, occurring in about 1% of all patients with Sjögren's syndrome. The patient's symptomatology and clinical course dictate current treatment of myelopathy. First-line treatment appears to be corticosteroid therapy. However, when the patient's condition fails to improve or deteriorates a nonsteroidal immunosuppressant agent should be considered. Agents used to treat myelopathy include cyclophosphamide, chlorambucil, azathioprine, ciclosporin (cyclosporin) and methotrexate in conjunction with corticosteroids. Most data exist as anecdotal reports. The agent of first choice, based on adverse effect profile and efficacy, appears to be cyclophosphamide given intravenously in pulse doses. Other nonsteroidal immunosuppressant agents should be considered, especially when lack of efficacy of, or intolerance to, cyclophosphamide exists in the patient's history. Glandular and other extraglandular symptoms may benefit concomitantly from the immunosuppressant treatment. In addition, when acute relief of symptomatology is needed, the patient may benefit from a trial of plasmapheresis or intravenous immunoglobulin. Infliximab (anti-tumour necrosis factor-alpha antibodies) has not been used as a treatment modality for myelopathy, but has shown some usefulness in the treatment of extraglandular symptoms, as well as peripheral nervous system manifestations of Sjögren's syndrome. This agent might be considered when all other treatment modalities have failed given the presumed importance of tumour necrosis factor in the pathogenesis of Sjögren's syndrome.

Clinical Trials as Topic↗
PubMed2003

Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial.

BACKGROUND AND PURPOSE: Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. METHODS: Patients (n=603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d (n=198), donepezil 10 mg/d (5 mg/d for first 28 days; n=206), or placebo (n=199). Analyses were based on the intent-to-treat population. RESULTS: At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale-cognitive subscale (mean change from baseline score effect size: donepezil 5 mg/d, -1.90; P=0.001; donepezil 10 mg/d, -2.33; P<0.001). Significant improvements in patients' global function were seen versus placebo at week 24 (observed cases), on the Clinician's Interview-Based Impression of Change-Plus version only for patients on donepezil 5 mg/d (P=0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d (P=0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale (mean change from baseline score effect size at week 24: donepezil 5 mg/d, -1.31, P=0.02; donepezil 10 mg/d, -1.31, P=0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low (placebo, 11.1%; donepezil 5 mg/d, 11.1%; donepezil 10 mg/d, 21.8%; P=0.005 versus placebo). CONCLUSIONS: These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition.

Activities of Daily Living↗