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Biomedical subjects

R Ylikoski

Publications and source records attributed to R Ylikoski.

At least 19 recordsLinked to original sources

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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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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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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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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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.

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Does apolipoprotein E influence learning and memory in the nondemented oldest old?

The objective of this study was to analyze the relationship of the apolipoprotein E (apoE) epsilon4 and epsilon2 alleles to learning and memory performances in the nondemented oldest old. Forty-six nondemented persons aged 85 years or over from a randomly selected group of 128 subjects in Vantaa, Finland, were studied. ApoE genotyping was performed using the minisequencing technique. A structured clinical examination and interview were carried out. The test variables studied were learning and memory scores (from the Fuld Object-Memory Evaluation), verbal fluency, and conceptualization (the Similarities subtest of the WAIS-R). We compared apoE-epsilon4 carriers to noncarriers and apoE-epsilon2 carriers to noncarriers. No statistically significant differences were found in any of the test variables. The results failed to confirm the hypotheses that poor cognitive performance is associated with the apoE-epsilon4 allele and good performance with the apoE-epsilon2 allele in the oldest old. This suggests that the apoE alleles do not have a detectable relationship to learning and memory in nondemented very elderly people.

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MRI correlates of dementia after first clinical ischemic stroke.

BACKGROUND AND PURPOSE: Dementia after first clinical stroke frequently has been found, but the clinical and radiological correlates have not been fully detailed. We examined magnetic resonance imaging (MRI) correlates of dementia in a large well-defined series of patients with first clinical ischemic stroke. METHODS: Detailed medical, neurological and neuropsychological examination was conducted 3 months after ischemic stroke for 273 patients with first clinical stroke from a consecutive series of 486 patients aged 55-85 years. MRI of the head categorised infarcts (type, site, side, number, volume), extent of white matter lesions (WMLs) and degree of atrophy. The DSM-III definition for dementia was used. RESULTS: Dementia was diagnosed in 79 (28.9%) of the patients with first clinical stroke. Volumes, numbers, distinct sites of infarcts, extent of WMLs and degree of atrophy were different for the demented and nondemented subjects. Logistic regression analysis showed that the correlates of dementia included the combination of infarct features (volume of infarcts in left-sided anterior corona radiata; OR 1.86), extent of WMLs (OR 1. 37), medial temporal lobe atrophy (OR 3.4) and host factors (low education; OR 1.11). The additive effect of having more than one correlate was detected (OR 2.53). CONCLUSIONS: Dementia occurring after first clinical stroke is frequent and not solely due to a single stroke, but contain a combination of infarcts features, extent of WMLs, medial temporal lobe atrophy and host factors reflecting more than one underlying pathology.

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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.

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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.

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Comparison of different clinical criteria (DSM-III, ADDTC, ICD-10, NINDS-AIREN, DSM-IV) for the diagnosis of vascular dementia. National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences.

BACKGROUND AND PURPOSE: The criteria for vascular dementia (VaD) include definition of the cognitive syndrome and the vascular cause. Different criteria for dementia identify different frequencies and clusters of patients. In addition, variation in defining the cause and etiology may have an effect. We compared different clinical criteria for VaD in series of patients with poststroke dementia. METHODS: The study group comprised 107 patients fulfilling the Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM-III) definition for dementia from a cohort of consecutive patients with ischemic stroke who completed a comprehensive neuropsychological test battery and MRI. The mean age (SD) of the patients was 71.4 (7.6) years. The definitions of vascular cause of VaD were those of the DSM-III (1980), Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC; 1992), International Statistical Classification of Diseases, 10th Revision (ICD-10; 1992), National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN; 1993), and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; 1994). RESULTS: The number of cases that could be classified as VaD according to the different criteria varied considerably: 36.4% (n=39) by DSM-III, 86.9% (n=93) by ADDTC, 32.7% (n=35) by NINDS-AIREN, 36.4% (n=39) by ICD-10, and 91.6% (n=98) by DSM-IV criteria. The concordance between DSM-III/ICD-10 was perfect (100%; kappa=1.0), between ICD-10/NINDS-AIREN and ADDTC/DSM-IV good to moderate (85.0% and 87. 3%; kappa=0.87 and 0.37, respectively), but otherwise poor between the other criteria. Only 31 patients fulfilled all the criteria for VaD applied. Major discriminating factors between the criteria were requirement of (1) focal neurological signs, (2) unequal distribution of deficits in higher cortical functions, and (3) evidence of relevant CVD based on brain imaging findings. CONCLUSIONS: Current criteria of VaD identify different frequencies and clusters of patients and are not interchangeable. Optimally, prospective studies with clinicopathological correlation could identify new criteria. Meanwhile, focus on more homogeneous subtypes (eg, small-vessel subcortical VaD) and detailed neuroimaging criteria could improve the diagnostics.

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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↗

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↗

A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1.

We describe a novel variant of Alzheimer's disease (AD) in a Finnish pedigree with 17 affected individuals of both sexes in three generations. The disease is characterized by progressive dementia which is, in most cases, preceded by spastic paraparesis. Neuropathological investigations revealed numerous, distinct, large, round and eosinophilic plaques as well as neurofibrillary tangles and amyloid angiopathy throughout the cerebral cortex. The predominant plaques resembled cotton wool balls and were immunoreactive for Abeta but lacked a congophilic dense core or marked plaque-related neuritic pathology. Molecular genetic analysis revealed that the disease was caused by a deletion of exon 9 (delta9) of the presenilin 1 (PS1) gene from the mRNA: unlike previous examples of the delta9 variant, the deletion was not caused by a splice acceptor site mutation.

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Clinical determinants of poststroke dementia.

BACKGROUND AND PURPOSE: Frequency of poststroke dementia is high, and stroke considerably increases the risk of dementia. The risk factors for dementia related to stroke are still incompletely understood. We sought to examine clinical determinants of poststroke dementia in a large well-defined stroke cohort. 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, neurological, 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. The DSM-III definition for dementia was used. RESULTS: Frequency of any poststroke dementia was 31.8% (107/337), that of stroke-related dementia (mixed Alzheimer's disease plus vascular dementia excluded) was 28.4% (87/306), and that of dementia after first-ever stroke was 28.9% (79/273). The patients with poststroke dementia were older and more often had a low level of education, history of prior cerebrovascular disease and stroke, left hemispheric stroke (reflecting laterality), major dominant stroke syndrome (reflecting laterality and size), dysphasia, gait impairment, and urinary incontinence. The demented patients were also more frequently current smokers, had lower arterial blood pressure values, and more frequently had an orthostatic reaction compared with the nondemented stroke patients. The correlates of dementia in logistic regression analysis were dysphasia (odds ratio [OR], 5.6), major dominant stroke syndrome (OR, 5.0), history of prior cerebrovascular disease (OR, 2.0), and low educational level (OR, 1.1). When we excluded those with cerebrovascular disease plus Alzheimer's disease or those with recurrent stroke, the order of correlates remained the same. When the patients with dysphasia (n=30) were excluded, the correlates were major dominant syndrome (OR, 4.6) and low educational level (OR, 1.1). CONCLUSIONS: Our data suggest that a single explanation for poststroke dementia is not adequate; rather, multiple factors including stroke features (dysphasia, major dominant stroke syndrome), host characteristics (educational level), and prior cerebrovascular disease each independently contribute to the risk.

Age Factors↗

Differences in neuropsychological functioning associated with age, education, neurological status, and magnetic resonance imaging findings in neurologically healthy elderly individuals.

In a cross-sectional study, a sample of 113 individuals, 55 to 85 years old, without any neurological diseases was investigated. The study provides information on differences associated with age, education, and gender, and in relation to neurological status, magnetic resonance imaging, and cognitive functioning. Differences between age groups were shown in memory, constructional, and language functions, and especially in tests related to speed and attention. Education was related to most of the cognitive functions, but especially to verbal intellectual functions, visual and logical memory, language functions, and calculation. Gender differences were found in finger tapping, constructional functions, and verbal intellectual functions. Primitive reflexes showed a tendency to correlate with comprehension and memory of sentences. Extrapyramidal signs were related to psychomotor speed, and attention, verbal fluency, and set shifting together with intellectual functions and learning. Central atrophy on magnetic resonance imaging was related to memory functions in those 65 and 70 years of age, whereas in the oldest age groups immediate recall was associated with the severity of lesions.

Journal Article↗

Functional assessment scales in detecting dementia.

AIM: to evaluate the use of different functional scales in detecting dementia in a population study. METHODS: the study is part of the Helsinki Ageing Study. A random sample of 795 subjects aged 75 (n = 274), 80 (n = 266) and 85 years (n = 255) was taken. The prevalences of dementia (DSM-III-R criteria) in these age groups were 4.6, 13.1 and 26.7% respectively. The functional scale scores were known for 71% of the non-demented and 66% of the demented subjects. A structured questionnaire completed by a close informant included four functional scales: the index of activities of daily living (ADL), the modified Blessed dementia scale (DS), the instrumental activities of daily living scale (IADL) and the Functional Assessment Questionnaire (FAQ). RESULTS: all the functional scales discriminated demented from non-demented subjects. Based on receiver operating characteristics analysis, the area under the curve (95% confidence interval) was 0.90 (0.80-0.94) for the ADL, 0.94 (0.87-0.97) for the DS, 0.95 (0.90-0.98) for the IADL and 0.96 (0.92-0.98) for the FAQ. The effects of age, sex and education in detecting dementia were minor or non-existent in the ADL, DS and FAQ scales, but age had an effect on the performance of the IADL scale. All the scales detected even mild dementia adequately. CONCLUSIONS: functional scales can be used in detecting dementia when functional assessment is already used for other purposes, such as among elderly primary care patients.

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Usefulness of the Clinical Dementia Rating scale in screening for dementia.

The Clinical Dementia Rating (CDR) scale is a qualitative staging instrument that has traditionally been used for assessing the severity of dementia. We used it for screening dementia in a population study of 75-, 80-, and 85-year-old people. The modified CDR scale was easy to establish and it proved to be useful in screening dementia. A more thorough examination is needed in the second phase to identify the false positives. The sensitivity of the CDR scale was 95% and the specificity 94%.

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