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Timo Erkinjuntti

Publications and source records attributed to Timo Erkinjuntti.

32 records · Page 2Linked to original sources
PubMed2003

An open-label extension trial of galantamine in patients with probable vascular dementia and mixed dementia.

BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are the most common types of dementia worldwide. Galantamine, an acetylcholinesterase inhibitor and allosteric nicotinic modulator, has shown broad clinical benefits in patients with mild to moderate dementia due to AD, probable VaD, or AD with cerebrovascular disease (CVD)-so-called mixed dementia. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety profiles of galantamine 24 mg/d in patients with VaD or AD with CVD over the longer term (>6 months). METHODS: This was an open-label extension of a 6-month double-blind study of galantamine. Patients who had been randomized to receive galantamine 24 mg/d or placebo in the double-blind phase were eligible to continue open-label treatment with galantamine 24 mg/d for 6 months. The primary efficacy end point was change in cognition, based on scores on the 11-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog/11). Secondary measures included changes in functional ability (as measured on the Disability Assessment for Dementia [DAD]) and behavior (as measured on the Neuropsychiatric Inventory [NPI]). Safety and tolerability were also monitored. RESULTS: Four hundred fifty-nine patients (240 men, 219 women; mean [SE] age, 75.2 [0.33] years) entered the open-label phase. Of these patients, 195 (42.5%) had a diagnosis of probable VaD, and 238 (51.9%) had a diagnosis of AD with CVD; the remainder had an inconclusive diagnosis. At month 12 of the study, improvements from baseline (the start of the double-blind phase) in ADAS-cog/11 scores were observed in both the group that received placebo during the double-blind phase (placebo/galantamine group: -0.3 point; 95% CI, -1.64 to 1.06) and the group that received galantamine during the double-blind phase (galantamine/galantamine group: -0.9 point; 95% CI, -1.73 to 0.03). Improvement in functional ability was demonstrated by statistically significant mean (SE) changes from baseline in DAD score in both the placebo/galantamine group (-7.4 [1.68]; P < or = 0.001) and the galantamine/galantamine group (-3.6 [1.33]; P < or = 0.01). There was no significant change in mean (SE) NPI scores in either group (0.2 [0.98] and 0.1 [0.70], respectively). Galantamine treatment was well tolerated. CONCLUSIONS: In these patients with VaD and AD with CVD, galantamine treatment produced similar sustained benefits in terms of maintenance of or improvement in cognition (ADAS-cog/11), functional ability (DAD), and behavior (NPI) after 12 months.

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PubMed2003

Vascular cognitive impairment.

Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.

Cerebrovascular Disorders↗
PubMed2003

Subcortical ischemic vascular disease and dementia.

Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischemic white-matter lesions (WMLs) as primary type of brain lesions, subcortical location as the primary location of lesions, and subcortical syndrome as the primary clinical manifestation. It incorporates two clinical entities: Binswanger's syndrome and the lacunar state. Patients with SIVD present with extensive white-matter lesions and multiple lacunae on neuroimaging. SIVD is expected to be a more homogenous subtype of vascular cognitive impairment and dementia. Recently modified NINDS-AIREN research criteria for SIVD have been proposed. Further empirical research is needed to refine the syndrome and stages and validate the brain imaging criteria, as well as to detail the natural history and outcomes of SIVD.

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PubMed2003

Classification and subtypes of vascular dementia.

Vascular dementia (VaD) is a heterogeneous entity with a large clinicopathological spectrum. It has been classified and subclassified in many different ways. The difficulty in identifying the various subtypes is a problem in the diagnostic process. For clinical purposes, it is desirable to find subtypes of VaD that are homogeneous enough to allow meaningful comparisons across studies. This article presents candidates for such subtypes: poststroke dementia, subcortical VaD, and combined Alzheimer's disease and VaD (AD + VaD). The first two candidates are easy to identify. Poststroke dementia occurs with cognitive decline in close temporal relation to a transient ischemic attack. Subcortical VaD has a relatively homogeneous clinical picture for which detailed criteria are suggested. AD + VaD is more difficult to identify but is possible, sometimes with the aid of neuroimaging and/or biological markers.

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PubMed2003

Vascular dementia.

Vascular dementia (VaD) is a term used to describe a particular constellation of cognitive and functional impairment, and is now generally seen as a subset of the larger syndrome of vascular cognitive impairment (VCI). The latter is seen as cognitive impairment in the face of cerebrovascular disease. VCI can be classified clinically by whether patients meet criteria for dementia, and whether the syndrome is distinct or overlaps with primary neurodegenerative diseases, such as Alzheimer's disease. This clinical classification can be further classified by neuroimaging, with subgroups that show cortical infarction, subcortical infarction and white matter changes, each alone or in combination. Understood in this way, VCI is likely the most common form of cognitive impairment in the population. Attempts to treat VaD had varying degrees of success, but it now appears that many forms of VCI might be preventable, especially with good control of vascular risk factors in middle age.

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PubMed2003

Generalized anxiety disorders three to four months after ischemic stroke.

BACKGROUND AND OBJECTIVE: The main objective of our study was to detail the frequency and clinical determinants of poststroke generalized anxiety disorders in a large, well-defined stroke cohort. METHODS: A total of 277 stroke patients aged 55-85 were subjected to a comprehensive psychiatric evaluation between 3 and 4 months after ischemic stroke. Primary generalized anxiety disorder or generalized anxiety disorder due to stroke were diagnosed according to DSM-IV symptom criteria. RESULTS: The frequency of any generalized anxiety disorder was 20.6% (n = 57). According to a logistic model, any generalized anxiety disorder was associated with a history of epilepsy, comorbid depressive disorder, severity of depression, severity of anxiety, and the use of anxiolytic drugs. A discriminant analysis identified four factors that distinguished the two diagnostic subgroups from one another: the level of psychosocial functioning (worse score in patients with generalized anxiety due to stroke), a history of migraine, anterior circulation stroke localization (more frequent in patients with generalized anxiety disorder due to stroke), and a history of insomnia (more frequent in patients with primary generalized anxiety disorder). CONCLUSIONS: Clinically significant anxiety is common in ischemic stroke patients and may hamper their rehabilitation.

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PubMed2003

Galantamine in the treatment of cognitive decline in patients with vascular dementia or Alzheimer's disease with cerebrovascular disease.

INTRODUCTION: Alzheimer's disease and vascular dementia are the two most common types of dementia, with significant overlap of clinical symptoms and pathology. Previous results from a 6-month, double-blind, placebo-controlled, international, multicentre study of the cholinomimetic galantamine in patients with probable vascular dementia or mixed dementia (Alzheimer's disease with cerebrovascular disease) showed significant cognitive, behavioural and functional benefits in these patients. Furthermore, results of a 6-month, open-label extension of this study confirmed that patients with vascular dementia or Alzheimer's disease with cerebrovascular disease may benefit from galantamine therapy for at least 1 year. The objective of the current analysis was to determine if the long-term cognitive benefits of galantamine seen in the above-mentioned study are influenced by dementia type (probable vascular dementia vs Alzheimer's disease with cerebrovascular disease). STUDY DESIGN: A post hoc sub-analysis of a 6-month, multicentre, randomised, double-blind, placebo-controlled study and a subsequent 6-month, open-label extension. PATIENTS AND METHODS: Patients diagnosed with probable vascular dementia or Alzheimer's disease with cerebrovascular disease were treated with galantamine (Reminyl) 24 mg/day for 12 months (6 months double-blind and 6 months open-label) or placebo for 6 months (double-blind) followed by galantamine 24 mg/day for 6 months (open-label). Changes in scores on the 11-item Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog/11) were assessed at months 6, 7.5 and 12. Mean changes from baseline were analysed. RESULTS: Patients with probable vascular dementia treated with galantamine for 6 or 12 months showed significant improvements in ADAS-cog/11 scores versus baseline, which were maintained at the end of the 12-month study. Patients who had Alzheimer's disease with cerebrovascular disease continuously treated with galantamine maintained the cognitive abilities seen at baseline for at least 12 months. Additionally, patients who had Alzheimer's disease with cerebrovascular disease who were switched from placebo to open-label galantamine therapy for 6 months demonstrated cognitive benefits, but these benefits were significantly less than those observed in patients treated with galantamine continuously for the 12-month period. Galantamine was well tolerated throughout the entire 12-month study. CONCLUSIONS: These findings suggest that the drug is efficacious for such common forms of dementia as vascular dementia and Alzheimer's disease with cerebrovascular disease. Moreover, some patients benefit from galantamine therapy that is initiated early, soon after diagnosis, and continued for at least 1 year.

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PubMed2002

Treatment options: the latest evidence with galantamine (Reminyl).

Vascular dementia (VaD) has a great deal of overlap (in terms of features and symptoms) with Alzheimer's disease (AD). Mixed dementia, or AD with concomitant cerebrovascular disease (AD with CVD), is increasingly being recognized as a distinct clinical condition that occurs with substantial frequency. The robust evidence for the effectiveness of cholinergic treatments such as galantamine (Reminyl) in AD suggests its potential use in the treatment of dementias related to CVD, and preclinical evidence supports this rationale. Galantamine, which has a unique dual cholinergic mode of action, may be of particular benefit in VaD and AD with CVD. For example, behavioral symptoms, which can be more severe in VaD than in AD and are important determinants of the impact of dementia, may be especially benefited by galantamine. This results from its potential to modulate systems involving other neurotransmitters such as 5-HT (serotonin) and dopamine, which affect mood and emotional balance. The results of a recent landmark clinical trial with galantamine in patients with VaD, or AD with CVD, indicate that galantamine produces benefits across a broad range of symptoms of dementia in both patient populations. Significant cognitive improvements over 6 months, long-term maintenance of cognition for at least 12 months, and global benefits, as well as efficacy in both behavioral and functional symptoms, indicate efficacy with galantamine that is so far unsurpassed by any other drug treatment for dementia. Galantamine therefore has potential to benefit a wide range of patients with dementia in the clinic.

Alzheimer Disease↗
PubMed2002

Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial.

BACKGROUND: Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer's disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer's disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer's disease combined with cerebrovascular disease. METHODS: Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer's disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician's interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward. FINDINGS: Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect 2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0.0001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0.002 and p=0.016, respectively). Galantamine was well tolerated. INTERPRETATION: Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.

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PubMed2002

Subcortical ischaemic vascular dementia.

Vascular dementia is the second most common type of dementia. The subcortical ischaemic form (SIVD) frequently causes cognitive impairment and dementia in elderly people. SIVD results from small-vessel disease, which produces either arteriolar occlusion and lacunes or widespread incomplete infarction of white matter due to critical stenosis of medullary arterioles and hypoperfusion (Binswanger's disease). Symptoms include motor and cognitive dysexecutive slowing, forgetfulness, dysarthria, mood changes, urinary symptoms, and short-stepped gait. These manifestations probably result from ischaemic interruption of parallel circuits from the prefrontal cortex to the basal ganglia and corresponding thalamocortical connections. Brain imaging (computed tomography and magnetic resonance imaging) is essential for correct diagnosis. The main risk factors are advanced age, hypertension, diabetes, smoking, hyperhomocysteinaemia, hyperfibrinogenaemia, and other conditions that can cause brain hypoperfusion such as obstructive sleep apnoea, congestive heart failure, cardiac arrhythmias, and orthostatic hypotension. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)and some forms of cerebral amyloid angiopathy have a genetic basis. Treatment is symptomatic and prevention requires control of treatable risk factors.

Brain↗
PubMed2002

Subcortical vascular dementia.

Vascular dementia (VaD) incorporates different vascular mechanisms and changes in the brain, and has different causes and clinical manifestations. Current criteria for VaD select an aetiologically and clinically heterogeneous group and this definitional heterogeneity has affected clinical trial results. Focus on a more homogeneous group, such as that with subcortical (ischaemic) VaD, could be an alternative in clinical drug trials. This subtype incorporates two small vessel clinical entities - 'Binswanger's disease' and 'the lacunar state'. It comprises small vessel disease as the primary vascular aetiology, lacunar infarct(s) and ischaemic white matter lesions as the primary type of brain lesions, subcortical location as the primary location of lesions, and the subcortical clinical syndrome as the primary clinical manifestation. Subcortical VaD is expected to show a more predictable clinical picture, natural history, outcome and treatment responses.

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PubMedDate not supplied

Clinical features of MRI-defined subcortical vascular disease.

BACKGROUND AND PURPOSE: Vascular cognitive impairment and vascular dementia are now seen to extend much beyond the traditional multi-infarct dementia.A more homogeneous subtype is the subcortical ischemic vascular disease (SIVD). We applied magnetic resonance imaging (MRI) criteria based on research criteria for SIVD in a large cohort of patients with ischemic stroke. We compared clinical features of patients with SIVD and patients with other stroke type. SUBJECT AND METHODS: The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischemic stroke completed a comprehensive neuropsychological test battery and MRI, including structured medical, neurologic, and laboratory evaluations; clinical mental status examination; interview of a knowledgeable informant; detailed history of risk factors; and evaluation of stroke type, localization, and syndrome. RESULTS: Patients with SIVD (n = 86) more often had a history of progressive cognitive decline (22.8% vs. 6.9%, P = 0.0002), walking disorder before stroke (27.9% vs. 2.0%, P = 0.02), and urinary difficulties (12.8% vs. 5.6%, P = 0.028) in comparison with patients with other stroke type (n = 251). Of the study population, 107 (31.8%) had DSM-III dementia. The patients with SIVD more often had DSM-III dementia (40.7% vs. 28.7%, P = 0.04), had less severe stroke as measured by Scandinavian Stroke Scale (56.6 vs. 55.1, P = 0.03), were more dependent in activities of daily living (ADL) functions as measured by FAQ scale (8.9 vs. 5.4, P = 0.001), were more dependent in instrumental activities of daily living (IADL) functions as measured by the Lawton scale (5.5 vs. 6.3, P = 0.01), and were more depressed as measured by the Beck Depression Inventory (11.8 vs. 8.4, P = 0.0003) poststroke than the patients without SIVD. The main cognitive domain that differentiated the patients with SIVD from those without was executive dysfunction (51.2% vs. 38.7%, P = 0.04). According to multiple regression model, apractic-atactic gait disorder (odds ratio 2.82, 95% confidence interval 1.21-6.53), ADL functions (odds ratio 1.04, 95% confidence interval 1.01-1.08), and the Beck Depression Inventory (odds ratio 1.05, 95% confidence interval 1.02-1.09) related to SIVD. CONCLUSIONS: The most significant clinical features of MRI-defined SIVD were found to be apractic-atactic gait, impaired ADL functions, and depression.

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