Biomedical subjects

M P Laakso

Publications and source records attributed to M P Laakso.

At least 19 recordsLinked to original sources

PubMed2006

Assessing the outcome of stroke: a comparison between MRI and clinical stroke scales.

OBJECTIVES: To assess the correlation of diffusion-weighted (DWI) and perfusion-weighted imaging (PWI) findings with the severity of acute neurologic deficit and their ability to predict short and long-term clinical outcomes of stroke. The ability of DWI and PWI to predict the outcome was compared with the ability of clinical stroke scales to predict the outcome. METHODS: Forty-eight patients with acute stroke underwent diffusion DWI and PWI on the first and eighth day after the ictus. Clinical and functional scales were carried out before each scan and 3 months after the stroke. RESULTS: The volumes of both the DWI and the PWI lesions correlated well with the acute neurologic deficit and the final outcome. The first day PWI (r = 0.64) and the National Institutes of Health Stroke Scale (NIHSS) scores (r = 0.70) correlated well with the final outcome. However, in logistic regression analysis, only the NIHSS score at the acute stage was the only independent predictor of the long-term clinical outcome. CONCLUSION: While the PWI and DWI lesion volumes correlated well with the outcome of the stroke, the imaging measurements did not improve the prognostic power over plain clinical stroke scale scores.

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PubMed2006

ApoE polymorphism and acute stroke: a study with diffusion- and perfusion-weighted MRI and MR angiography.

OBJECTIVES: We examined whether the apolipoprotein E (ApoE) allele epsilon4 influences imaging findings in stroke as assessed by diffusion- (DWI) and perfusion-weighted (PWI) magnetic resonance imaging, and MR angiography (MRA). METHODS: Eight ApoE epsilon4 carriers and 15 non-carriers with acute ischemic stroke in the anterior circulation underwent DWI, PWI, and MRA within 24 h of stroke. DWI and PWI were repeated a week later. The apparent diffusion coefficient, relative cerebral volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time were measured in three subregions on day one. RESULTS: In the ischemic core and the area of infarct growth, rCBV values were significantly higher in the epsilon4 carriers compared with the non-carriers. Based on the MRA findings, collateral blood flow was better in the epsilon4 carriers than in the non-carriers. Under the comparable severity of hypoperfusion, the hypoperfused area proceeded to infarction later or did not proceed to infarction at all in the non-carriers. CONCLUSION: These preliminary data suggest that in the ApoE allele epsilon4 carriers the threshold for the brain tissue to survive hypoperfusion versus to proceed to infarction seems to be different from that of the non-carriers.

Acute Disease↗

PubMed2005

Structural correlates of early and late onset Alzheimer's disease: voxel based morphometric study.

OBJECTIVE: To examine the brain structural correlates of age at onset in patients with Alzheimer's disease. METHODS: We studied nine patients with early onset (age < or =65 years), nine with late onset (age > 65) Alzheimer's disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age < or =65, n = 9) and older (OC, age > 65, n = 17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic. RESULTS: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype. CONCLUSIONS: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer's neuropathology.

Age of Onset↗

PubMed2005

A voxel based morphometry study on mild cognitive impairment.

BACKGROUND: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. OBJECTIVE: To study the pattern of brain atrophy in MCI. METHODS: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p < 0.001. RESULTS: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere-for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. CONCLUSIONS: The MRI findings in MCI resemble those seen in early AD.

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PubMed2004

Serum testosterone levels in males with Alzheimer's disease.

This study aimed to investigate whether there are differences in serum testosterone levels between male patients with Alzheimer's disease (AD) and cognitively normal male controls. Testosterone and sex hormone binding globulin (SHBG) levels were measured from 14 patients with mild to moderate AD and 16 age-matched control males. The AD patients had higher levels of serum total (P = 0.02) and free testosterone (P < 0.001), and higher free androgen index (FAI) (P = 0.02) compared to controls. No differences were found for the SHBG levels. These data provide no support for hypotheses of (disproportionally) decreased levels of serum testosterone in AD. These data also show that all cognitively normal controls had an FAI below the normal range.

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PubMed2004

Hippocampal MRI volumetry in cognitively discordant monozygotic twin pairs.

OBJECTIVE: To investigate whether hippocampal atrophy, a proxy for incipient Alzheimer's disease, can be detected in non-demented monozygotic co-twins of demented twins by using volumetric magnetic resonance imaging (MRI). METHODS: Seven pairs of monozygotic female twins discordant for cognitive function (mean (SD) age 75 (4) years), and 10 age and education matched healthy controls (seven women, three men; mean age 73 (3) years) were studied with volumetric MRI. RESULTS: The mean normalised right hippocampal volume was 31% lower (p = 0.002) in the demented twins, and 6% lower (p = 0.45) in the non-demented twins than in the controls. In the left hippocampus, the mean normalised volume was 36% lower (p<0.001) in the demented twins, and 9% lower (p = 0.13) in the non-demented twins than in the controls. CONCLUSIONS: Significant hippocampal atrophy was detected in the demented twins compared with the controls. This is in line with previous imaging and pathological studies, with hippocampus showing the early changes in Alzheimer's disease. In the non-demented twins, only a minor, non-significant reduction was observed in the hippocampal volumes compared with the controls. This could reflect gene-environment interactions that have protected the non-demented twins longer than their demented co-twins and contributed to the relative preservation of their hippocampal volumes, or it could be a sign of preclinical Alzheimer's disease in the non-demented twins.

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PubMed2003

Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers.

Apolipoprotein E (ApoE) genotype has been shown to influence results in neuroimaging studies using a number of various imaging modalities. No in vivo data exists on whether or not there are ApoE-related changes observable by proton magnetic resonance spectroscopy (MRS). In this study we measured absolute peak areas of proton MR spectra obtained from the occipital cortex in 22 non-demented elderly with (n = 8) or without (n = 14) the ApoE epsilon4 allele. No statistically significant differences were found in levels of N-acetyl aspartate, myo-inositol, or choline containing compounds between the groups. Instead, compared with the non-carriers, the levels of creatine were significantly lower in the epsilon4 carriers, suggesting increased metabolic demands in the brain of the epsilon4 carriers. The levels of creatine also correlated significantly with age and performance on the Mini-Mental State Examination test in the epsilon4 carriers, but not in the non-carriers. These findings may be of significant clinical interest as potential indicator of incipient AD, and also from therapeutical point of view given the potential neuroprotective effects of creatine.

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PubMed2003

Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease.

Post mortem studies have revealed a loss of dopamine D2 receptors in the temporal lobes in Alzheimer's disease (AD). Moreover, the role of hippocampal D2 receptors on memory performance has been suggested in experimental studies. However, there are no previous in vivo studies on extrastriatal D2 receptors in AD. Our aim was to examine in vivo whether hippocampal or temporal cortical dopamine D2 receptors are affected in AD and whether D2 receptor availability is associated with the memory dysfunction seen in AD. Fourteen patients with probable AD and 11 age- and sex-matched controls were studied with positron emission tomography using a dopamine D2/D3 receptor antagonist [(11)C]FLB 457. The D2 receptor binding potentials (BPs) were measured in extrastriatal brain regions and a neuropsychological investigation was performed on the patients with AD. In AD, the D2 receptor availability was reduced in the hippocampus: by 34% (P = 0.03) in the right hippocampus and by 14% (P = 0.78) in the left hippocampus as compared with controls. Multiple linear regression analysis showed that the BP in the right hippocampus had a significant positive association with verbal memory performance (Wechsler Memory Scale - Revised) (P = 0.001) and picture naming (the Boston Naming Test) (P = 0.002). Our findings suggest a role for temporal lobe D2 receptors in the memory and naming performance in AD, and suggest that studies to evaluate the efficiency of dopaminergic medication on patients with early AD might be warranted.

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PubMed2002

Amygdaloid atrophy in frontotemporal dementia and Alzheimer's disease.

Crude and corrected amygdaloid volumes were computed from magnetic resonance scans in ten patients with frontotemporal dementia (FTD), 25 patients with Alzheimer's disease (AD) and 27 controls. Amygdaloid atrophy was present in FTD (P<0.005) compared to controls, and a trend for increasing atrophy from controls, through FTD to AD (P for trend <0.00005) showed that FTD amygdaloid volumes were intermediate between controls and AD. Behavioral and Klüver-Bucy-like symptoms, characteristic of FTD, cannot be explained by amygdaloid atrophy alone.

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PubMed2002

Effects of subcortical ischemic vascular dementia and AD on entorhinal cortex and hippocampus.

OBJECTIVE: To determine the effects of subcortical ischemic vascular dementia (SIVD) and AD on entorhinal cortex (ERC) and hippocampus. METHODS: Thirty-eight cognitively normal subjects, 18 patients with SIVD, and 22 patients with AD were included. Volumes of ERC and hippocampus were manually measured based on MRI. Global cerebral changes of cortical gray matter, subcortical gray matter, white matter, sulcal CSF, ventricular CSF (vCSF), and white matter signal hyperintensities (WMSH) were assessed. RESULTS: Patients with SIVD had 21.7% (p < 0.01) smaller ERC and 18.2% (p < 0.01) smaller hippocampi than cognitively normal subjects and 24.4% (p < 0.01) larger ERC and 11.1% (p < 0.05) larger hippocampi than patients with AD. In addition, patients with SIVD had less cortical gray matter and white matter and more vCSF and WMSH (all p < 0.01) than cognitively normal subjects and more vCSF and WMSH (p < 0.01) than patients with AD. The volumes of ERC and hippocampus were positively correlated to similar extents (p < 0.01) in SIVD and AD. Cortical gray matter loss was positively correlated (p < 0.01) with hippocampal atrophy, but not with ERC atrophy, in SIVD and AD. Hippocampal volume alone could classify 82% of patients with SIVD from cognitively normal subjects and 63% of patients with SIVD from subjects with AD. Adding global cerebral changes to hippocampus substantially improved the classification to 96% between patients with SIVD and cognitively normal subjects and 83% between subjects with SIVD and those with AD, whereas adding ERC change to hippocampus did not significantly improve the discrimination. CONCLUSIONS: The entorhinal cortex and hippocampus are less affected by subcortical ischemic vascular dementia than by AD.

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PubMed2002

Detection of grey matter loss in mild Alzheimer's disease with voxel based morphometry.

OBJECTIVES: To test the applicability of an automated method of magnetic resonance image analysis (voxel based morphometry) to detect presence and severity of regional grey matter density reduction-a proxy of atrophy-in Alzheimer's disease. METHODS: Twenty nine probable Alzheimer's patients and 26 non-demented controls (mini-mental state examinations mean (SD) 21 (4) and 29 (1)) underwent high resolution 3D brain magnetic resonance imaging. Spatial normalisation to a stereotactic template, segmentation into grey matter, white matter, and cerebrospinal fluid, and smoothing of the grey matter were carried out based on statistical parametric mapping (SPM99) algorithms. Analyses were carried out: (a) contrasting all Alzheimer's patients with all controls (p<0.05 corrected for multiple comparisons); (b) contrasting the three Alzheimer's patients with mini-mental state of 26 and higher with all controls (p<0.0001 uncorrected); and (c) correlating grey matter density with mini-mental state score within the Alzheimer's group (p<0.0001 uncorrected). RESULTS: When all Alzheimer's patients were compared with controls, the largest atrophic regions corresponded to the right and left hippocampal/amygdalar complex. All parts of the hippocampus (head, body, and tail) were affected. More localised atrophic regions were in the temporal and cingulate gyri, precuneus, insular cortex, caudate nucleus, and frontal cortex. When the mildest Alzheimer's patients were contrasted with controls, the hippocampal/amygdalar complex were again found significantly atrophic bilaterally. The mini-mental state score correlated with grey matter density reduction in the temporal and posterior cingulate gyri, and precuneus, mainly to the right. CONCLUSIONS: Voxel based morphometry with statistical parametric mapping is sensitive to regional grey matter density reduction in mild Alzheimer's disease.

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PubMed2001

Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study.

OBJECTIVE: To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer's Disease Research Center. BACKGROUND: MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. RESULTS: Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (> or =6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. CONCLUSION: Data point to a role for midlife vascular risk factors in the development of MCI in late life.

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PubMed2001

Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study.

OBJECTIVE: To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer's disease in later life. DESIGN: Prospective, population based study. SETTING: Populations of Kuopio and Joensuu, eastern Finland. PARTICIPANTS: Participants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years' follow up, a total of 1449 (73%) participants aged 65-79 took part in the re-examination in 1998. MAIN OUTCOME MEASURES: Midlife blood pressure and cholesterol concentrations and development of Alzheimer's disease in later life. RESULTS: People with raised systolic blood pressure (>/=160 mm Hg) or high serum cholesterol concentration (>/=6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer's disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer's disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer's disease. CONCLUSION: Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer's disease in later life.

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PubMed2001

A morphometric MRI study of the hippocampus in first-episode, neuroleptic-naïve schizophrenia.

Magnetic resonance imaging (MRI) studies have frequently, although not unambiguously, reported hippocampal volume deficit in schizophrenia. Data on the hippocampal volumes in first-episode schizophrenia, however, are sparse. In addition, a recent topographic MRI study proposed a regionally specific volume loss in the hippocampus of chronic schizophrenics, but to date no reports have replicated this finding. In this study two-dimensional MRI-based topographic brain mapping was used to study the possibility of regional changes in the hippocampus of 22 controls and 18 patients with first-episode, neuroleptic-naïve schizophrenia. Compared to controls, there were no significant differences between hippocampal volumes, regional volumes, or length of the hippocampus in the patients with schizophrenia. These data are at odds with the previous reports on hippocampal volume loss in first-episode schizophrenia, and with the hypothesis of regionally specific hippocampal volume deficit in schizophrenia.

Adult↗

PubMed2001

APOE-epsilon4 is associated with weight loss in women with AD: a population-based study.

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.

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PubMed2001

Psychopathy and the posterior hippocampus.

Neurobiology of psychopathy is of interest, not only because neural underpinnings of psychopathy remain obscure, but also because psychopaths may provide a model to study violent behavior, neurology of morals and impaired decision-making. Medial temporal lobe pathology has been suggested to be a part of the neural systems dysfunction which manifests as violent and psychopathic behavior. Yet, so far no sound evidence of neuroanatomical correlates for psychopathic behavior has been found. In this study regional hippocampal volumes were measured using magnetic resonance imaging in 18 habitually violent offenders with antisocial personality disorder and type 2 alcoholism (derived from forensic psychiatric evaluation). The regional volumes along the anteroposterior axis of the hippocampus were correlated with the subjects' degree of psychopathy as evaluated by the Psychopathy Checklist-Revised. Strong negative correlations, up to -0.79, were observed, among the study subjects, between the psychopathy scores and the posterior half of the hippocampi bilaterally. These data are in accordance with experimental studies proposing that lesions of the dorsal hippocampus impair acquisition of conditioned fear, and with theories on psychopathology according to which one of the central features in the birth of psychopathy is a deficit in acquisition of conditioned fear.

Adult↗

PubMed2001

Magnetic resonance imaging of the entorhinal cortex and hippocampus in mild cognitive impairment and Alzheimer's disease.

OBJECTIVES: To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups. METHODS: This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation. RESULTS: Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC. CONCLUSIONS: Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.

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PubMed2000

Hippocampus and entorhinal cortex in frontotemporal dementia and Alzheimer's disease: a morphometric MRI study.

BACKGROUND: Magnetic resonance imaging (MRI) of hippocampal atrophy is a sensitive but not specific method to support the clinical diagnosis of early Alzheimer's disease (AD). We recently described our findings that atrophy of the entorhinal cortex (ERC) in frontotemporal dementia (FTD) is equal to that found in AD but that hippocampal atrophy in FTD is less than that found in AD. The MRI volumes of these structures provide a topographic representation of the region of interest. We hypothesized that two different dementias with distinct histopathologic and clinical features might, in addition to quantitative patterns, display topographically different patterns of atrophy. METHODS: We adopted a morphometric approach to monitor the pattern of atrophy of the hippocampus and the ERC by computing two-dimensional profiles from MRI volumes of the structures in control subjects and patients with FTD and AD. RESULTS: Compared with control subjects, atrophy of the hippocampus in patients with AD was diffuse. In patients with FTD, atrophy of the hippocampus was localized predominantly in the anterior hippocampus, suggesting a different pattern of hippocampal atrophy in FTD compared with AD. The amount and pattern of atrophy of the entorhinal cortex was virtually equal in both demented groups. CONCLUSIONS: This study provides novel data on the nature of medial temporal lobe atrophy in FTD. Morphometric MRI may be a useful technique for characterizing different patterns of atrophy in primary degenerative dementias in vivo.

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