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Biomedical subjects

T Erkinjuntti

Publications and source records attributed to T Erkinjuntti.

At least 19 recordsLinked to original sources
PubMed2000

Efficacy and safety of nimodipine in subcortical vascular dementia: a subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial.

In Western countries, vascular dementia (VaD) is the most common form of cognitive deterioration after Alzheimer's disease. Therapeutic trials in VaD have so far failed to yield satisfactory results. One explanation of this failure may be the etiological and clinical heterogeneity of the included patients. Patients with subcortical VaD, defined on a clinical and radiological basis, may constitute a more homogeneous group. Thus, we conducted a post-hoc subgroup analysis of the Scandinavian Multi-Infarct Dementia Trial that evaluated the efficacy and safety of oral nimodipine administered for 6 months in 259 patients. The original patients sample was divided on the basis of head CT in those with subcortical VaD (n=92, 45 nimodipine, 47 placebo) and those with multi-infarct dementia (n=167, 83 nimodipine, 84 placebo). While in the total trial population a treatment effect could not be proved, in this subgroup analysis, the subcortical VaD patients treated with nimodipine performed better on the majority of neuropsychological tests and functional scales in comparison with patients on placebo. No trend could be evidenced in the multi-infarct dementia patients. Treatment efficacy was in particular suggested for the Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency, and for the Instrumental Activities of Daily Living scale. The results did not reach statistical significance in this small sample. Our study preliminarily indicates that nimodipine could be effective in patients with small vessel subcortical VaD and supports the rationale for a further controlled and adequately powered trial to test nimodipine in patients with subcortical VaD.

Activities of Daily Living↗
PubMed2000

The Scandinavian Multi-Infarct Dementia Trial: a double-blind, placebo-controlled trial on nimodipine in multi-infarct dementia.

Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Brâne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.

Aged↗
PubMed2000

How complex interactions of ischemic brain infarcts, white matter lesions, and atrophy relate to poststroke dementia.

BACKGROUND: Cerebrovascular disease is a major factor related to cognitive impairment. However, behavioral correlates of ischemic brain lesions are insufficiently characterized. OBJECTIVE: To examine magnetic resonance imaging correlates of dementia in a large, well-defined series of patients with ischemic stroke. METHODS: Detailed medical, neurological, and neuropsychological examinations were conducted 3 months after ischemic stroke for 337 of 486 consecutive patients aged 55 to 85 years. Infarcts (type, site, side, number, and volume), extent of white matter lesions (WMLs), and degree of atrophy were categorized according to magnetic resonance images of the head. The definition for dementia of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) was used. RESULTS: Dementia was diagnosed in 107 (31.8%) of the patients and stroke-related dementia in 87 (25.8%). Volumes, numbers, distinct sites of infarcts, extent of WMLs, and degree of atrophy were different for the demented and nondemented subjects. Particularly, volumes of infarcts in any (right- or left-sided) superior middle cerebral artery territory (27.3 vs 13.7 cm(3), P =. 002) and left thalamocortical connection (14.8 vs 4.0 cm(3), P =. 002) differentiated the 2 groups. Logistic regression analysis showed that the correlates of any dementia included the combination of infarct features (volume of infarcts in any superior middle cerebral artery: odds ratio [OR], 1.11; frequency of left-sided infarcts: OR, 1.21), extent of WMLs (OR, 1.3), medial temporal lobe atrophy (OR, 2.1), and host factors (education; OR, 0.91). In the patients with stroke-related dementia, the main correlate was volume of infarcts in the left anterior corona radiata (OR, 1.68). CONCLUSION: Correlates of poststroke dementia do not include merely 1 feature but a combination of infarct features, extent of WMLs, medial temporal lobe atrophy, and host features.

Aged↗
PubMed2000

Research criteria for subcortical vascular dementia in clinical trials.

Vascular dementia (VaD) incorporate different vascular mechanisms and changes in the brain, and have different causes and clinical manifestations. Variation in defining the cognitive syndrome, in vascular etiologies, and allowable brain changes in current clinical definitions of VaD have resulted in variable estimates of prevalence, of groups of subjects, and of the types and distribution of putative causal brain lesions. Thus current criteria for VaD select an etiologically and clinically heterogeneous group. This definitional heterogeneity may have been a factor in "negative" clinical trials. An alternative for clinical drug trials is to focus on a more homogeneous group, such as those with subcortical (ischemic) VaD. This designation incorporates two small vessel clinical entities "Binswanger's disease" and "the lacunar state". It comprises small vessel disease as the primary vascular etiology, lacunar infarct(s) and ischaemic white matter lesions as the primary type of brain lesions, and subcortical location as the primary location of lesions. The subcortical clinical syndrome is the primary clinical manifestation, a definition which still requires additional empirical data. We expect that subcortical VaD show a more predictable clinical picture, natural history, outcome, and treatment responses. We propose a modification of the NINDS-AIREN criteria as a new research criteria for subcortical VaD.

Clinical Trials as Topic↗
PubMed2000

Hippocampal and temporal lobe atrophy and age-related decline in memory.

OBJECTIVES: To evaluate the relationship of memory decline that accompanies aging with structural changes in the medial temporal lobe, in healthy middle-aged and older subjects. MATERIAL AND METHODS: A sample of 35 neurologically non-diseased subjects, between 55 and 70 years of age, were examined in a 5-year follow-up study. Neuropsychological investigation included tests of learning, verbal memory, and visual memory. MRI was performed with a superconducting MRI system operating at 1.0 T, using coronal slices of T1-weighted images. Medial temporal lobe atrophy was rated separately in the neocortical, entorhinal and hippocampal regions. RESULTS: We did not find any statistically significant relationship between mild hippocampal or temporal atrophy and memory test performance. Nor did the longitudinal decline in memory show a relationship with temporal lobe atrophy. CONCLUSIONS: The main outcome of our study was that age-related memory decline was not related to mild temporal lobe atrophy in healthy subjects without mild cognitive impairment. There could be other factors influencing memory functions besides age-related structural changes in temporal lobes.

Aged↗
PubMed2000

Limitations of clinical criteria for the diagnosis of vascular dementia in clinical trials. Is a focus on subcortical vascular dementia a solution?

Vascular dementia (VaD) includes several different vascular mechanisms and changes in the brain, and has different causes and clinical manifestations. Critical to its conceptualization and diagnosis are definitions of the cognitive syndrome, vascular etiologies, and changes in the brain. Variation in these has resulted in different definitions of VaD, estimates of prevalence, and types and distribution of brain lesions. This definitional heterogeneity may have been a factor for negative results in prior clinical trials on VaD. We propose that the division of VaD into subtypes can identify a more homogeneous group of patients for drug trials. A so-called "subcortical" VaD could incorporate two old clinical entities "Binswanger's disease" and "the lacunar state." Small vessel disease is the primary vascular etiology, lacunar infarcts and ischemic white matter lesions are the primary type of brain lesions, the subcortical areas and frontal connections are the primary location of lesions, and a subcortical syndrome as the primary clinical manifestation. The clinical syndromes are likely more variable, and urgently need to be categorized. Selection of these patients for clinical trials could mainly be based on brain imaging features, where the essential changes and the main aspects of the lesions include extensive ischemic white matter lesions and lacunar infarcts in the deep gray and white matter structures. Subcortical VaD is expected to show a more predictable clinical picture, natural history, outcomes, and treatment responses.

Brain↗
PubMed2000

Subcortical vascular dementia as a specific target for clinical trials.

Vascular cognitive impairment is considered the second most common form of mental deterioration in the elderly after degenerative dementias. Therapeutic approaches to vascular dementia mainly rely on the identification and treatment of risk factors. A number of drugs have also been tested with the aim of improving or slowing cognitive decline in patients affected by various forms of cerebrovascular disease. Most of these trials have yielded unsatisfactory results. We hypothesize that some of these failures depend on the inclusion of patients with pathophysiologically heterogeneous types of vascular cognitive decline. In this paper, we review some of the most important trials that tested drugs with a preventive or therapeutic aim in vascular dementia patients. Preliminary results suggest that some beneficial effects can be detected only when the trial population is homogeneous on a clinical and pathogenic basis. In particular, subcortical vascular dementia, a form with a rather univocal clinical, radiological, and pathological picture, seems a particularly apt choice as a target for future clinical studies. At present, only one therapeutic trial is being conducted in patients affected by this specific form of vascular dementia.

Aged↗
PubMed2000

MRI pontine hyperintensity after supratentorial ischemic stroke relates to poor clinical outcome.

BACKGROUND AND PURPOSE: MRI studies in patients with atherosclerosis often reveal ill-defined hyperintensity in the pons on T2-weighted images. This pontine hyperintensity (PHI) does not fulfill the criteria of a brain infarct, and its clinical relevance is not established. We examined the frequency, as well as the radiological and clinical correlates, of PHI in poststroke patients. METHODS: Three hundred nineteen patients were studied 3 months after supratentorial ischemic stroke with the use of 1.0-T MRI. Brain infarcts, atrophy, white matter hyperintensities, and PHI were registered. The clinical outcome was assessed 3 and 15 months after the stroke. RESULTS: Of the patients, 152 (47.6%) had PHI. The risk factors for stroke did not differ in patients without or with PHI. PHI was related to a higher frequency (P=0.002) and larger volume (P<0.001) of supratentorial brain infarcts, to parietal (P=0.020) and temporal (P=0.002) atrophy, to central atrophy (P< or =0.040), and to white matter hyperintensity grade (P<0.001). Brain infarcts that affected the corpus striatum (putamen, caudate, and pallidum) (P< or =0. 011) or pyramidal tract (P<0.001) were more frequent in patients with PHI. The 3- and 15-month outcomes were worse in patients with PHI (P< or =0.004). The total volume of brain infarcts (OR 1.22), mean atrophy (OR 3.59), and PHI (OR 3.76) were independent correlates of a poor 15-month outcome. CONCLUSIONS: PHI after supratentorial ischemic stroke deserves attention because it relates to poor clinical outcome.

Activities of Daily Living↗
PubMed1999

The prevalence and distribution of white-matter changes on different MRI pulse sequences in a post-stroke cohort.

No uniform criteria currently exist for rating white-matter (WM) high-signal foci on MRI. Ratings are based on descriptive terms, different pulse sequences and different WM areas. Reports on the prevalence and clinical correlates of high-signal foci have been contradictory. We wanted to examine the contribution of the pulse sequence and WM area on rating WM changes. We analysed WM changes separately on T2-, protondensity (PD)- and T1-weighted images in periventricular, subcortical, watershed area and deep WM. The difference between T2- and PD-weighted images was significant for frontal caps, counting small foci or analysing subcortical changes. T1-weighted images showed significantly less change, but the number of foci detected was greater than previously thought. The prevalence of WM high-signal foci was greatest in the watershed zone and smallest in the subcortical area. There was a significant correlation between foci in different areas.

Aged↗
PubMed1999

Impaired preconscious auditory processing and cognitive functions in Alzheimer's disease.

OBJECTIVE: To study whether preconscious auditory processing is deteriorated in patients with Alzheimer's disease (AD) having mild to moderate cognitive symptoms. To investigate whether auditory processing correlates with the impairment of the higher cortical functions. METHODS: P50m and N100m responses elicited by a sequence of repetitive tones were recorded with a whole-head magnetometer from 22 patients with probable AD and from 18 healthy age-matched controls. In addition, an extensive neuropsychological test battery assessing main cognitive domains was administered to all subjects. RESULTS: The patients with AD had significantly delayed N100m responses in the left hemisphere that correlated with the impairment of the language functions. CONCLUSIONS: N100m auditory responses measured with magnetoencephalography may be useful in evaluating the severity and progression of the cortical dysfunction in dementia.

Aged↗
PubMed1999

Heterogeneity of cognitive profiles in aging: successful aging, normal aging, and individuals at risk for cognitive decline.

Neuropsychological clinical decision-making is complicated by the fact that variability in test performance increases with advancing age. This research explores the presence of homogeneous subgroups in 120 neurologically healthy individuals, from 55 to 85 years of age. Subjects at risk for dementing diseases were diagnosed as Aging-Associated Cognitive Decline (AACD) and Mild Cognitive Impairment (MCI). Cluster analysis was applied on 11 neuropsychological variables assessing logical memory immediate recall and retention percentage, visual memory immediate recall and retention, conceptual thinking, naming, verbal fluency, constructional functions, motor speed, flexibility and finger tapping. Five clusters were extracted, one representing cognitively successfully aged, and two consisting of individuals with normal or average level of performance. One cluster was characterized by older subjects with difficulties in visual memory, visuoconstructional functions, and speed and attention, most of the younger subjects in the same cluster had a diagnosis of AACD or MCI. The fifth cluster represented individuals at risk for dementing diseases; most of them were diagnosed having AACD and more than half had a diagnosis of MCI. Age, activity and intellectual levels, and to a lesser degree education, were significantly related to the cluster solution. The present findings caution against treating samples of elderly individuals as homogeneous.

Age Factors↗
PubMed1999

Executive functions and speed of mental processing in elderly patients with frontal or nonfrontal ischemic stroke.

Impairments in executive functions have been related to aging and frontal lobe lesions. Aging also causes slowing of mental processing. We examined whether ischemic stroke in the frontal brain area results in dysexecutive syndrome, or whether the frontal stroke causes increased slowing of mental processing. Neurological, radiological and neuropsychological examinations were carried out 3 months post-stroke on 250 ischemic stroke patients (55-85 years) and on 39 healthy control subjects. Of the patients, 62 had frontal and 188 had nonfrontal lesions. The neuropsychological examination comprised several cognitive domains, including tests considered to measure executive functions. The frontal group was slower than the nonfrontal group in tasks measuring speed of mental processing which were time-limited (Trail Making A, Stroop dots and fluency). They were also inferior in the Digit Span backwards task. There were no differences between the groups in other cognitive domains, nor in some tests which are considered to be measures of executive functions (e.g. WCST). Impairments in executive functions were evident in both the frontal and the nonfrontal groups compared with the controls, but no dysexecutive syndrome specifically related to frontal lesions was found. Frontal stroke related mainly to the slowing of mental processing.

Age Factors↗
PubMed1999

Clinical and radiological determinants of prestroke cognitive decline in a stroke cohort.

OBJECTIVES: Stroke seems to be related to dementia more often than previously assumed and vascular factors are also related to Alzheimer's disease. The pathophysiology of poststroke dementia includes ischaemic changes in the brain, a combination of degenerative and vascular changes, and changes only related to Alzheimer's disease. Some cognitive decline recognised after a stroke may be due to pre-existing cognitive decline. The aim of this study was to determine the clinical and radiological determinants of prestroke cognitive decline. METHODS: The study group comprised 337 of 486 consecutive patients aged 55 to 85 years who 3 months after ischaemic stroke completed a comprehensive neuropsychological test battery; structured medical, neurological, and mental status examination; interview of a knowledgeable informant containing structured questions on abnormality in the cognitive functions; assessment of social functions before the index stroke; and MRI. RESULTS: Frequency of prestroke cognitive decline including that of dementia was 9.2% (31/337). The patients with prestroke cognitive decline were older, more often had less than 6 years of education, and had history of previous stroke. Vascular risk factors did not differ significantly between these two groups. White matter changes (p=0.004), cortical entorhinal, hippocampal, and medial temporal atrophy (p<0.001), cortical frontal atrophy (p=0.008); and any central atrophy (p<0.01), but not the frequencies or volumes of old, silent, or all infarcts on MRI differentiated those with and without prestroke cognitive decline. The correlates of prestroke cognitive decline in logistic regression analysis were medial temporal cortical atrophy (odds ratio (OR) 7.5, 95% confidence interval (95%CI) 3.2-18.2), history of previous ischaemic stroke (OR 4.4, 95% CI 1.8-10.6), and education (OR 0.9, 95% CI 0.8-0.9). CONCLUSIONS: History of previous stroke, but not volumes or frequencies was found to correlate with prestroke cognitive decline. Other associating factors were rather those usually associated with degenerative dementia: white matter changes and cerebral atrophy; and in multiple models medial temporal cortical atrophy and education. The possible overlap between two or more underlying diseases must be remembered in diagnosis and treatment of patients with vascular cognitive impairment.

Aged↗
PubMed1999

White matter changes in stroke patients. Relationship with stroke subtype and outcome.

White matter changes (WMC), detected by imaging techniques, are frequent in stroke patients. The aim of the study was to determine how WMC relate to stroke subtypes and to stroke outcome. We made a systematic Medline search for articles appearing with two of the following key words: either 'WMC or white matter lesions or leukoencephalopathy or leukoaraiosis' and 'stroke or cerebral infarct or cerebral hemorrhage or cerebrovascular disease or transient ischemic attack (TIA)'. WMC, as defined radiologically, are present in up to 44% of patients with stroke or TIA and in 50% of patients with vascular dementia. WMC are more frequent in patients with lacunar infarcts, deep intracerebral hemorrhages, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and cerebral amyloid angiopathy. After an acute ischemic stroke, WMC are associated with a higher risk of death or dependency, recurrent stroke of any type, cerebral bleeding under anticoagulation, myocardial infarction, and poststroke dementia. WMC in stroke patients are often associated with small-vessel disease and lead to a higher risk of death, and poor cardiac and neurological outcome. However, several questions remain open and need further investigations.

Age Factors↗
PubMed1999

Magnetic resonance imaging white matter hyperintensities and mechanism of ischemic stroke.

BACKGROUND AND PURPOSE: We sought to determine the relations between infarct subtype and white matter hyperintensities (WMHIs) on MRI. MATERIALS AND METHODS: We studied 395 ischemic stroke patients with 1. 0-T MRI. The number of lacunar, border-zone, and cortical infarcts was registered. WMHIs were analyzed in 6 areas. Univariate and multivariate statistical analyses were used to find the risk factors for different infarct subtypes and to study the connections between WMHIs and brain infarcts. RESULTS: Lacunar infarcts were associated with hypertension (odds ratio [OR], 1.79; 95% CI, 1.17 to 2.73), alcohol consumption (OR, 1.96; 95% CI, 1.17 to 3.28), and age (OR, 1. 03; 95% CI, 1.00 to 1.06). Border-zone infarcts were associated with carotid atherosclerosis (OR, 2.20; 95% CI, 1.15 to 4.19). Atrial fibrillation (OR, 3.02; 95% CI, 1.66 to 5.50) and carotid atherosclerosis (OR, 1.94; 95% CI, 1.12 to 3.36) were independent positive predictors, and history of hyperlipidemia (OR, 0.44; 95% CI, 0.26 to 0.75) and migraine (OR, 0.48; 95% CI, 0.25 to 0.93) were negative predictors for cortical infarcts. Patients with lacunar infarcts had more severe WMHIs than patients with nonlacunar infarcts in all WM areas (P</=0.001). Patients with border-zone infarcts showed severe periventricular lesions (P=0.002), especially around posterior horns (P=0.003). The extent of WMHIs in patients with cortical infarcts did not differ from that in those without cortical infarcts. CONCLUSIONS: Various infarct subtypes have different risk profiles. The association between lacunar infarcts and WMHIs supports the concept of small-vessel disease underlying these 2 phenomena. The connection between border-zone infarcts and periventricular WMHIs again raises the question of the disputed periventricular vascular border zone.

Aged↗
PubMed1998

Rapid apolipoprotein E genotyping from mailed buccal swabs.

Genetic polymorphism of apolipoprotein E (apoE) is linked with the risk of cardiovascular and Alzheimer's disease (AD). We determined apoE genotypes from mailed buccal cell swabs in 36 healthy individuals and 18 demented patients suffering from AD. DNA was released from the swabs by a rapid lysis technique. Polymerase chain reaction using 'hot start' and restriction enzyme digestion by HhaI was used for genotyping of apoE alleles, which were detected by polyacrylamide or MetaPhor agarose gel. ApoE genotypes determined from buccal cells or from stored leucocytes were identical to previously done phenotyping. An advantage of the present simplified buccal cell collection procedure is the possibility to collect DNA samples for apoE genotyping rapidly by mail from patients visiting their physician geographically distant from research laboratory. Moreover, venepuncture and storing of the samples in refrigerators are avoided and costs are reduced. This non-invasive and painless method is also applicable to other genetic screening tests in risk populations.

Adult↗
PubMed1998

Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease.

The epsilon 4 allele of the apolipoprotein E (apoE) is associated with Alzheimer's disease (AD) and also with elevated serum total cholesterol and low-density lipoprotein levels. However, the interrelationships between apoE genotype, plasma cholesterol levels and AD risk have been studied very little. We examined the possible role of serum total cholesterol in the pathogenesis of AD in a population-based sample of 444 men, aged 70-89 years, who were survivors of the Finnish cohorts of the Seven Countries Study. Previous high serum cholesterol level (mean level > or = 6.5 mmol/l) was a significant predictor of the prevalence of AD (odds ratio = 3.1; 95% confidence interval = 1.2, 8.5) after controlling for age and the presence of apoE epsilon 4 allele. In men who subsequently developed AD the cholesterol level decreased before the clinical manifestations of AD. We conclude that high serum total cholesterol may be an independent risk factor for AD and some of the effect of the apoE epsilon 4 allele on risk of AD might be mediated through high serum cholesterol.

Adult↗