Biomedical subjects

T Erkinjuntti

Publications and source records attributed to T Erkinjuntti.

At least 19 recordsLinked to original sources

PubMed2006

Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study.

BACKGROUND: White matter hyperintensities (WMH) on MRI are associated with disorders of gait and balance and with cognitive impairment. The most suitable method to assess WMH in relation to the clinical evaluation of disturbances in these areas has not yet been established. AIM: To compare a simple visual rating scale, a detailed visual rating scale and volumetric assessment of WMH with respect to their associations with clinical measures of physical performance and cognition. METHODS: Data were drawn from the multicentre, multinational LADIS study. Data of 574 subjects were available. MRI analysis included assessment of WMH using the simple Fazekas scale, the more complex Scheltens scale and a semi-automated volumetric method. Disturbances of gait and balance and general cognitive function were assessed using the Short Physical Performance Battery (SPPB) and the Mini Mental State Examination (MMSE), respectively. RESULTS: Irrespective of the method of measuring WMH, subjects with disturbances of gait and balance (SPPB < or = 10) had more WMH than subjects with normal physical performance. Subjects with mild cognitive deficits (MMSE < or = 25) had more WMH than subjects with normal cognition. Correlations between clinical measures and WMH were equal across methods of WMH measurement (SPPB: Spearman r = -0.22, -0.25, -0.26, all p < 0.001; MMSE: Spearman r = -0.11, -0.10, -0.09, all p < 0.05, for Fazekas scale, Scheltens scale and volumetry, respectively). These associations remained significant and comparable after correcting for age, gender and education in multivariate linear regression analyses. CONCLUSION: Simple and complex measures of WMH yield comparable associations with measures of physical performance and cognition. This suggests that a simple visual rating scale may be sufficient, when analyzing relationships between clinical parameters and WMH in a clinical setting.

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PubMed2006

Clinical significance of corpus callosum atrophy in a mixed elderly population.

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.

Age Factors↗

PubMed2006

Cognitive profile of subcortical ischaemic vascular disease.

OBJECTIVES: Subcortical ischaemic vascular disease (SIVD) is a subtype of vascular cognitive impairment characterised by extensive white matter lesions and multiple lacunar infarcts. Radiologically defined diagnostic criteria for SIVD have been introduced, but only a few studies have presented empirical data on its clinical and cognitive features. The aim of this study is to describe in detail the neuropsychological characteristics of patients with SIVD from a large well defined stroke cohort. METHODS: A sample of 323 consecutive patients with ischaemic stroke, aged 55-85 years, was investigated using neuropsychological examination and magnetic resonance imaging (MRI). Patients fulfilling the MRI criteria of SIVD (n = 85) were compared to the other stroke patients (n = 238) and to normal control subjects (n = 38). RESULTS: Cognitive performance of the SIVD group was inferior to that of the normal control group throughout all domains. As compared to the other stroke patients, the SIVD group performed significantly worse in tests measuring executive functions and delayed memory recall. Adjusting for depression had no effect on these results. Instead, after controlling for medial temporal lobe atrophy, the differences disappeared for delayed memory but remained significant for executive functions. CONCLUSION: Executive deficits are the most prominent cognitive characteristic associated with SIVD. Patients with SIVD also exhibit subtle deficits in delayed memory, which is explained in part by medial temporal lobe atrophy. Cognitive and mood changes seem to be parallel but independent processes related to SIVD. The results support the concept of SIVD as a separate clinical entity.

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PubMed2005

White matter hyperintensities as a predictor of neuropsychological deficits post-stroke.

OBJECTIVES: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients. METHODS: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses. RESULTS: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions. CONCLUSIONS: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.

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PubMed2005

Medial temporal lobe atrophy and white matter hyperintensities are associated with mild cognitive deficits in non-disabled elderly people: the LADIS study.

OBJECTIVE: To assess the associations of medial temporal lobe atrophy (MTA) and white matter hyperintensities (WMH) with cognitive function in a large group of independently functioning elderly people. METHODS: Data were drawn from the multicentre, multinational leukoaraiosis and disability (LADIS) project which is studying prospectively the role of WMH as an independent predictor of the transition to disability in non-disabled elderly people. In all, 639 participants were enrolled in the LADIS study. For the present analysis, data on 581 subjects were available. Cognitive function was assessed by the mini-mental state examination (MMSE). Visual ratings of WMH and MTA were undertaken on magnetic resonance images (MRI). RESULTS: The presence of either severe WMH or MTA was associated with a modest but non-significant increase in frequency of mild cognitive deficits (severe WMH: odds ratio (OR) = 1.9 (95% confidence interval (CI), 1.0 to 3.7); MTA present: OR = 1.5 (95% CI, 0.8 to 2.8)). However, subjects with the combination of MTA and severe WMH had a more than fourfold increase in frequency of mild cognitive deficits (OR = 4.1 (95% CI, 2.3 to 7.4)). Analysis of variance with post hoc Bonferroni t tests showed that subjects with both MTA and severe WMH performed worse on MMSE than those with either no MRI abnormality or a single MRI abnormality (p<0.05). CONCLUSIONS: These results provide further evidence for the combined involvement of both Alzheimer type pathology and vascular pathology in the earliest stages of cognitive decline and suggest an additive effect of WMH and MTA.

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PubMed2004

White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease.

There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.

Arterioles↗

PubMed2004

Mild cognitive impairment--beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment.

The First Key Symposium was held in Stockholm, Sweden, 2-5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

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PubMed2004

Medial temporal lobe atrophy and memory deficits in elderly stroke patients.

Medial temporal lobe atrophy (MTA) and its role in memory deficits have been studied extensively in patients with various dementias and non-degenerative neurologic diseases. In stroke patients MTA is a significant risk factor for dementia. However, its role in memory decline in non-demented stroke patients is not yet known. Our aim was to evaluate the relationship between MTA and cognitive functions in a large cohort of elderly patients, who underwent a comprehensive neuropsychologic examination and magnetic resonance imaging 3 months after an ischemic stroke. The study sample (n = 260) was divided into three groups according to the severity of MTA. After adjusting for age, volume of infarcts and cortical atrophy, we found that patients with moderate to severe MTA performed significantly worse in tests of learning, story recall, visual reproduction, block design and mental speed. In contrast, the groups did not differ in tests of digit span, flexibility, verbal fluency and conceptualization. Our conclusion is that in aged stroke patients, MTA is associated with poor performance in specific cognitive domains. The most vulnerable domains are memory and visuospatial functions, whereas verbal and executive functions seem to be unrelated to MTA.

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PubMed2004

Poststroke depression and lesion location revisited.

Seventy patients with one brain infarct on magnetic resonance imaging (MRI) were studied 3 months after ischemic stroke by a standardized protocol to detail side, site, type, and extent of the brain infarct, as well as severity of white matter lesions and brain atrophy. Depression was diagnosed by DSM-III-R and DSM-IV criteria. The brain infarcts that affected structures of the frontal-subcortical circuits, (i.e., the pallidum and caudate, especially on the left side) predisposed stroke patients to depression. The size of the infarcts at these sites in the depressed patients was larger. Using a logistic regression analysis, the authors found that a brain infarct that affected pallidum was a strong independent MRI correlate for poststroke depression (odds ratio = 7.2).

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PubMed2003

Fibrinogen gene promoter -455 A allele as a risk factor for lacunar stroke.

BACKGROUND AND PURPOSE: Elevated fibrinogen levels are suggested to increase the risk of myocardial infarction and stroke. Carriers of the A allele of the fibrinogen -455G/A polymorphism have increased plasma fibrinogen levels. We studied the association of this polymorphism with stroke subtype in the Stroke Aging Memory (SAM) cohort. METHODS: The SAM cohort comprises 486 consecutive patients 55 to 85 years of age who, 3 months after ischemic stroke, completed a detailed stroke assessment. Stroke subtypes were examined with MRI. -455G/A genotype was determined by polymerase chain reaction. MRI and genotype data were available for the 299 patients who constitute the present study population. RESULTS: Genotype distributions were 64.9% (GG), 31.8% (GA), and 3.3% (AA). In a logistic regression model with age, sex, hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, myocardial infarction, arrhythmia, atrial fibrillation, peripheral arterial disease, and smoking as possible confounders, there was a significant association between A+ genotype and >or=3 lacunar infarcts (odds ratio [OR], 2.57; 95% CI, 1.23 to 5.36; P=0.01). Hypertensive patients carrying the A allele had increased risk (OR, 4.24; 95% CI, 1.29 to 13.99; P=0.02) for >or=3 lacunar infarcts. A similar increase in risk was observed among smokers with the A+ genotype (OR, 2.67; 95% CI, 0.92 to 7.77; P=0.07). CONCLUSIONS: Stroke patients carrying the A allele of the Bbeta-fibrinogen -455G/A polymorphism frequently presented with multiple lacunar infarcts. This association was stronger among hypertensives and smokers. These associations suggest that the A allele may predispose to atherothrombotic events in cerebrovascular circulation.

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PubMed2003

Semantic decision making in early probable AD: a PET activation study.

We studied the neural correlates of semantic decision making in early probable Alzheimer disease patients and age-matched controls by measuring changes in relative cerebral blood flow by PET (oxygen-15) while they performed a category-specific word-matching task with either animal or artefact names. In comparison to a baseline (matching words by physical identity), semantic decision making elicited increased blood flow in the left frontal lobe (BA 6, 11, 47) and in the contralateral cerebellum in the controls. The only category-specific difference in controls was activation of the left supplementary motor area (BA 6) when making decisions on artefacts. In contrast, the patients recruited more extensive brain regions, encompassing areas in the left frontal lobe (BA 44, 45, 47), right occipital cortex (BA 18), midbrain, and the cerebellum bilaterally. Behaviorally, the patients performed the tasks with equal success albeit more slowly. No animal-artefact differences emerged in the patients' activation patterns, indicating that their activation increases reflected a generalized, presumably compensatory reaction to higher task demands in the face of a progressive neurological disease.

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PubMed2003

MRI correlates of executive dysfunction in patients with ischaemic stroke.

Executive dysfunction (ED) may lead to problem behaviour and impaired activities of daily living in many neuropsychiatric disorders, but the neuroanatomical correlates of ED are still not well known. Different aspects of executive functions were studied by widely used neuropsychological tests in 214 elderly patients 3 months after ischaemic stroke, and a sum score of eight different measures was counted in each patient. The number and site of brain infarcts as well as severity and location of white matter lesions (WMLs) and brain atrophy on magnetic resonance imaging were recorded and compared between patients with and without ED. ED was present in 73 (34.1%) of the 214 patients. The mean frequency of brain infarcts in the brain and in the left hemisphere was higher in the patients with ED. Lesions affecting the frontal-subcortical circuits (e.g. pallidum, corona radiata or centrum semiovale) were more frequent in patients with ED than in those without. Also, patients with pontine brain infarcts frequently had ED, but this may have been due to more extensive ischaemic changes in these patients in general. Mean number of brain infarcts affecting the pons and posterior centrum semiovale on the left side, moderate to severe medial temporal atrophy, the Fazekas white matter score, the Mini-Mental State Examination score and low education were independent correlates of ED. Brain infarcts and WML affecting the frontal-subcortical circuits or the pons may increase risk for ED in stroke patients.

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PubMed2003

Long-term safety and cognitive effects of galantamine in the treatment of probable vascular dementia or Alzheimer's disease with cerebrovascular disease.

The relationship between cholinergic dysfunction and cognitive and functional impairment in patients with vascular dementia (VaD) and Alzheimer's disease (AD) with cerebrovascular disease (CVD) suggests a potential role for cholinomimetic therapy. Initial studies of galantamine demonstrated cognitive, behavioral, and functional benefits in these populations. 326 patients with VaD or AD with CVD who completed an initial 12-month trial were treated with galantamine 24 mg/day in a 24-month, open-label extension. This interim analysis was performed at month 12 of the open-label extension (248 completed the trial). Galantamine (up to 24 months total) was well tolerated in both groups. The most frequently reported adverse events, characteristic of older dementia patients, included depression, agitation, and insomnia. Gastrointestinal adverse events were less common than initially, indicating declining incidence with long-term therapy. Patients taking galantamine for the entire study demonstrated the least cognitive decline on AD Assessment Scale-cog/11: 2.7 points vs. 3.1 points in those given placebo initially (P < 0.001 and P = 0.003, respectively). The long-term benefits of galantamine were evident in both groups; cognitive baseline levels were maintained for approximately 21 months in VaD patients and for 12 months in patients with AD with CVD. Long-term (up to 24 months) galantamine therapy in patients with VaD and AD with CVD is well tolerated and associated with prolonged maintenance of cognitive function.

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PubMed2003

Alcohol misuse: a risk factor for putaminal damage by ischemic brain infarct?

The relationship between alcohol consumption and the risk of ischemic stroke has been widely studied, whereas the effect of alcohol use on stroke features is not well established. This study compared the clinical and stroke features of ischemic stroke in two groups of patients with ischemic stroke: those with a history of alcohol misuse and those with a history of more social drinking. DSM-IV criteria were used to diagnose alcohol use disorder (dependency or abuse) in 275 of 486 consecutive patients aged 55-85 years, 3-4 months after ischemic stroke. Magnetic resonance imaging of the head was performed 3 months after stroke. Alcohol use disorder was diagnosed in 37/275 (13.5%) of ischemic stroke patients. These patients had more frequently (70.3 vs. 34.5%; OR 4.5; 95% CI 2.2-9.1; p < 0.000) an infarct affecting the putamen compared with patients who indulged in more social drinking. Another predisposed area was the superior anterior cerebral artery area. The stroke due to large- artery atherosclerosis was more common in patients with alcohol use disorder. The misuse of alcohol seemed to be associated with cerebral infarct localization in the putamen and superior anterior cerebral artery area. Prospective studies are needed to verify our preliminary finding.

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PubMed2003

Potential long-term effects of rivastigmine on disease progression may be linked to drug effects on vascular changes in Alzheimer brains.

Alzheimer's disease patients with hypertension or other vascular risk factors have been shown to receive greater symptomatic benefits than patients with strictly Alzheimer's disease following short-term treatment with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase. We evaluated the long-term efficacy of rivastigmine in Alzheimer's disease patients with or without hypertension. Subjects in a 26-week placebo-controlled trial of rivastigmine entered an open-label extension study for 104 weeks. Efficacy measures included the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Progressive Deterioration Scale (PDS) and Global Deterioration Scale (GDS). Subjects were stratified by the presence or absence of hypertension at baseline. At 104 weeks, there was a trend for hypertensive patients from the original rivastigmine 6-12 mg/day group (early starters), who received rivastigmine for the full 104 weeks) to have better ADAS-cog scores than the original placebo group (late starters), who received open-label rivastigmine for the last 78 weeks only). Significant treatment differences were observed in the hypertensive subgroup on the PDS and GDS. In non-hypertensive patients, changes from baseline at week 104 were similar in 'early' and 'late' starters of rivastigmine treatment. The additional apparent benefits on disease progression detected in patients with hypertension and Alzheimer's disease may be linked to drug effects on cerebrovascular factors. These findings may have an important influence on the way cholinesterase inhibitors are prescribed.

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PubMed2002

Diagnosis and management of vascular cognitive impairment and dementia.

Vascular dementias (VaDs) are the second most common cause of dementia. Cerebrovascular disease (CVD) and stroke relates to high risk of cognitive impairment, but also relate to Alzheimer's disease (AD): Vascular cognitive impairment (VCI) and dementias extend beyond the traditional multi-infarct dementia. Pathophysiology of VaD incorporates interactions between vascular etiologies (CVD and vascular risk-factors), changes in the brain (infarcts, white matter lesions, atrophy), host factors (age, education) and cognition. Variation in defining the cognitive syndrome, in vascular etiologies, and allowable brain changes in current criteria have resulted in variable estimates of prevalence, of groups of subjects, and of the types and distribution of putative causal brain lesions. Should new criteria be developed? Ideally in constructing new criteria the diagnostic elements should be tested with prospective studies with clinical-pathological correlation: replace dogma with data. Meanwhile focus on more homogenous subtypes of VaD, and on imaging criteria could be a solution. Subcortical ischemic vascular disease and dementia (SIVD) incorporate small vessel disease as the chief vascular etiology, lacunar infarct and ischaemic white matter lesions 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 disease" and "the lacunar state". AD with VaD (mixed dementia) has been underestimated as a prevalent cause in the older population. In addition to simple co-existence, VaD and AD have closer interaction: several vascular risk factors and vascular brain changes relate to clinical manifestation of AD, and they share also common pathogenetic mechanisms. Vascular cognitive impairment (VCI) is a category aiming to replace the "Alzhemerized" dementia concept in the setting of CVD, and substitute it with a spectrum that includes subtle cognitive deficits of vascular origin, post-stroke dementia, and the complex group of the vascular dementias. As far there is no standard treatment for VaDs, and still little is known on the primary prevention (brain at risk for CVD) and secondary prevention (CVD brain at risk for VCI/VaD). There is no standard symptomatic treatment for VaD. Recently symptomatic cholinergic treatment has shown promise in AD with VaD, as well as probable VaD. Future focus should be directed to the distinct etiological and pathological factors: the vascular and the AD burden of the brain.

Alzheimer Disease↗

PubMed2002

Cognitive decline and treatment options for patients with vascular dementia.

Cognitive impairment is the primary symptom of vascular dementia (VaD). Animal and human studies indicate that, as with Alzheimer's disease (AD), deficits in cholinergic transmission -- including nicotinic receptor binding abnormalities -- may be responsible for the development of cognitive impairment associated with VaD. Therefore, studies of acetylcholinesterase inhibitors (AChEIs) have been initiated and have shown promising results to date. These agents have demonstrated cognitive and global benefits in patients with VaD. Additionally, functional and behavioral benefits have been reported with the dual-mechanism AChEI galantamine. These studies suggest a potential role for AChEIs in the management of cognitive impairment associated with VaD.

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PubMed2002

Post-stroke depression, executive dysfunction and functional outcome.

The early diagnosis of vascular cognitive impairment has been challenged and executive control function has been suggested to be a rational basis for the diagnosis of vascular dementia. We sought to examine the correlates of executive dysfunction in a well-defined stroke cohort. A group of 256 patients from a consecutive cohort of 486 patients with ischaemic stroke, aged 55-85 years, was subjected to a comprehensive neuropsychological examination 3-4 months after ischaemic stroke and 188 of them in addition to detailed psychiatric examination. Basic and complex activities of daily living (ADLs) (bADLs and cADLs) post-stroke were assessed. The DSM-III-R criteria were used for the diagnosis of the depressive disorders. Altogether 40.6% (n=104) of the patients had executive dysfunction. The patients with executive dysfunction were older, had lower level of education, were more often dependent, did worse in bADLs and cADLs, had more often DSM-III dementia, had worse cognition as measured by Mini Mental State Examination (MMSE) and were more depressed as measured by the BECK depression scale, but not with the more detailed psychiatric evaluation. They had more often stroke in the anterior circulation and less often in the posterior circulation. The independent correlates of executive dysfunction were cADLs (OR 1.1, 95% CI 1.03-1.16), each point of worsening in cognition by MMSE (OR 1.7, 95% CI 1.42-1.97) and stroke in the posterior circulation area (OR 0.4, 95% CI 0.18-0.84). Clinically significant executive dysfunction is frequent after ischaemic stroke and is closely connected with cADLs and to overall cognitive status but could be distinguished from depression by detailed neuropsychological examination. Executive measures may detect patients at risk of dementia and disability post-stroke.

Activities of Daily Living↗