Biomedical subjects

Juha O Rinne

Publications and source records attributed to Juha O Rinne.

At least 19 recordsLinked to original sources

PubMed2007

Brain function during multi-trial learning in mild cognitive impairment: a PET activation study.

We explored functional brain changes with positron emission tomography (PET) in mild cognitive impairment (MCI) patients and elderly normal controls by employing an episodic memory task that included two successive encoding trials of semantically related word-pairs and final retrieval. Both groups demonstrated significant learning across the two trials. The control group showed predominantly left frontal activity during encoding, and right frontal plus left temporal activity during retrieval. However, the MCI patients recruited partly different brain regions. They failed to activate right frontal and left temporal areas during retrieval, and failed to show any different activation for encoding on the first and second trials, whereas the controls activated a region of posterior cingulate. There was indication of compensatory increases in rCBF of the occipital cortex during incremental learning and the left frontal lobe during retrieval in the patients. These results suggest different episodic memory processing in the MCI group, and a possible over-reliance on semantic processing. Subtle functional changes occur in the pre-Alzheimer brain before there are marked structural or behavioural abnormalities.

Aged↗

PubMed2007

Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans.

UNLABELLED: We investigated the biodistribution and radiation dosimetry of the PET amyloid imaging agent (11)C-PIB ((11)C-6-OH-BTA-1) (where BTA is benzothiazole) in humans. Previous radiation exposure estimates have been based on animal experiments. A dosimetry study in humans is essential for a balanced risk-benefit assessment of (11)C-PIB PET studies. METHODS: We used data from 16 different (11)C-PIB PET scans on healthy volunteers to estimate radiation exposure. Six of these scans were dynamic imaging over the abdominal region: 3 covering the upper abdomen and 3 covering the middle abdomen. On average, 489 MBq of (11)C-PIB (range, 416-606 MBq) were injected intravenously, and dynamic emission scans were recorded for up to 40 min. Two subjects had whole-body imaging over the entire body to illustrate the biodistribution. PET brain scans and blood and urine radioactivity measurements from our previous (11)C-PIB studies were also analyzed. Thirteen source organs and the remainder of the body were studied to estimate residence times and mean radiation-absorbed doses. The MIRD method was used to calculate the radiation exposure of selected target organs and the body as a whole. RESULTS: There is a high degree of consistency between our human data and previous biodistribution information based on baboons. In our study, the highest radiation-absorbed doses were received by the gallbladder wall (41.5 microGy/MBq), liver (19.0 microGy/MBq), urinary bladder wall (16.6 microGy/MBq), kidneys (12.6 microGy/MBq), and upper large intestine wall (9.0 microGy/MBq). The hepatobiliary and renal systems were the major routes of clearance and excretion, with approximately 20% of the injected radioactivity being excreted into urine. The effective radiation dose was 4.74 microSv/MBq. CONCLUSION: The established clinical dose of (11)C-PIB required for 3-dimensional PET amyloid imaging has an acceptable effective radiation dose. This dose is comparable with the average exposure expected in other PET brain receptor tracer studies. (11)C-PIB is rapidly cleared from the body, largely by the kidneys. From the viewpoint of radiation safety, these results support the use of (11)C-PIB in clinical PET studies.

Adult↗

PubMed2006

Cost-utility model of rasagiline in the treatment of advanced Parkinson's disease in Finland.

BACKGROUND: The economic burden of Parkinson's disease (PD) is high, especially in patients experiencing motor fluctuations. Rasagiline has demonstrated efficacy against symptoms of PD in early and advanced stages of the disease. OBJECTIVE: To assess the cost-utility of rasagiline and entacapone as adjunctive therapies to levodopa versus standard levodopa care in PD patients with motor fluctuations in Finland. METHODS: A 2 year probabilistic Markov model with 3 health states: "25% or less off-time/day," "greater than 25% off-time/day," and "dead" was used. Off-time represents time awake with poor or absent motor function. Model inputs included transition probabilities from randomized clinical trials, utilities from a preference measurement study, and costs and resources from a Finnish cost-of-illness study. Effectiveness measures were quality-adjusted life years (QALYs) and number of months spent with 25% or less off-time/day. Uncertainty around parameters was taken into account by Monte Carlo simulations. RESULTS: Over 2 years from a societal perspective, rasagiline or entacapone as adjunctive therapies to levodopa showed greater effectiveness than levodopa alone at no additional costs. Benefits after 2 years were 0.13 (95% CI 0.08 to 0.17) additional QALYs and 5.2 (3.6 to 6.7) additional months for rasagiline and 0.12 (0.08 to 0.17) QALYs and 5.1 (3.5 to 6.6) months for entacapone, both in adjunct to levodopa compared with levodopa alone. CONCLUSIONS: The results of this study support the use of rasagiline and entacapone as adjunctive cost-effective alternatives to levodopa alone in PD patients with motor fluctuations in Finland. With a different mode of action, rasagiline is a valuable therapeutic alternative to entacapone at no additional charge to society.

Antiparkinson Agents↗

PubMed2006

Mobile phone affects cerebral blood flow in humans.

Mobile phones create a radio-frequency electromagnetic field (EMF) around them when in use, the effects of which on brain physiology in humans are not well known. We studied the effects of a commercial mobile phone on regional cerebral blood flow (rCBF) in healthy humans using positron emission tomography (PET) imaging. Positron emission tomography data was acquired using a double-blind, counterbalanced study design with 12 male subjects performing a computer-controlled verbal working memory task (letter 1-back). Explorative and objective voxel-based statistical analysis revealed that a mobile phone in operation induces a local decrease in rCBF beneath the antenna in the inferior temporal cortex and an increase more distantly in the prefrontal cortex. Our results provide the first evidence, suggesting that the EMF emitted by a commercial mobile phone affects rCBF in humans. These results are consistent with the postulation that EMF induces changes in neuronal activity.

Adult↗

PubMed2006

Striatal subregional 6-[18F]fluoro-L-dopa uptake in early Parkinson's disease: a two-year follow-up study.

Thirty-one drug-naive patients with Parkinson's disease (PD) underwent 6-[18F]fluoro-L-dopa (F-dopa) positron emission tomography (PET) scan at the time of the diagnosis (baseline) and 2 years later in order to investigate F-dopa uptake in striatal and extrastriatal regions during the first years of early PD. Twenty-four healthy controls underwent one F-dopa PET scan. The regional differences in the striatal and extrastriatal regions were analyzed with statistical parametric mapping and automated region of interest analyses. Our study shows that the F-dopa uptake in unmedicated early PD is most severely decreased in the dorsal part of caudal putamen but significant decrease can be seen throughout the striatum compared with controls. During the first years of PD, there is a progressive regional decline in striatal F-dopa uptake, the dorsal part of caudal putamen being still the most severely affected region. The absolute decline is equal between the striatal subregions. This suggests that the decline of dopamine function starts from the dorsocaudal putamen, but once started, the rate of progression is equal between the subregions of the striatum. In contrast to the striatal decline, the increased cortical F-dopa uptake prevails at least during the first years of PD.

Aged↗

PubMed2006

No association between the brain-derived neurotrophic factor 196 G>A or 270 C>T polymorphisms and Alzheimer's or Parkinson's disease.

The brain-derived neurotrophic factor (BDNF) promotes survival, differentiation and maintenance of neurons in the central nervous system. BDNF 196 G>A and 270 C>T polymorphisms have previously been associated with Alzheimer's disease (AD) and with Parkinson's disease (PD). To study the role of BDNF 196 G>A and 270 C>T polymorphisms in Finnish AD and PD patients we genotyped BDNF 196 G>A and 270 C>T polymorphisms in 97 sporadic AD patients, 52 PD patients and 101 control subjects with polymerase chain reaction. No associations were found between the genotypes studied and AD or PD in Finnish patients. Moreover, no interaction between either BDNF polymorphism and the epsilon 4 allele of apolipoprotein E was found. In conclusion, it seems that the BDNF gene does not contribute significantly to the risk of AD or PD in Finnish patients.

Aged↗

PubMed2005

Brain oscillatory responses to an auditory-verbal working memory task in mild cognitive impairment and Alzheimer's disease.

We report preliminary findings on EEG oscillatory correlates of working memory in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Event-related desynchronization (ERD) and synchronization (ERS) of the 1-20 Hz EEG frequencies were studied using wavelet transforms in elderly controls, MCI patients and mild probable AD patients performing an auditory-verbal Sternberg memory task. Behaviourally, the AD patients made more errors than the controls and the MCI group. Statistically significant differences during the encoding of the memory set were found between the controls and the MCI group, such that the latter group showed ERD in the approximately 10-20 Hz frequencies. The findings may reflect different, compensatory encoding strategies in MCI. During retrieval, the most obvious differences were observed between the controls and the AD group: the ERD in the approximately 7-17 Hz frequencies was absent in the AD group particularly in anterior and left temporal electrode locations. This finding might indicate that AD is associated with deficient lexical-semantic processing during the retrieval phase in working memory tasks. Future studies with larger patient groups are needed to establish the diagnostic value of ERD/ERS patterns in MCI and AD.

Acoustic Stimulation↗

PubMed2005

Frontal and temporal dopamine release during working memory and attention tasks in healthy humans: a positron emission tomography study using the high-affinity dopamine D2 receptor ligand [11C]FLB 457.

Experimental studies on animals have shown that dopamine is a key neurotransmitter in the regulation of working memory (WM) functions in the prefrontal cortex. In humans, blood flow studies show prefrontal involvement in WM functions, but direct evidence for the involvement of the dopaminergic system in WM is lacking. Using positron emission tomography with a recently developed high-affinity dopamine D2 receptor tracer, [11C]FLB 457, we explored frontal, temporal, and parietal D2 receptor availability in 12 healthy volunteers while they were performing verbal WM and sustained attention tasks. During the performance of both tasks, reduced D2 receptor availability was observed in the left ventral anterior cingulate, suggesting an attention or arousal-related increase in dopamine release during these tasks. Compared with the sustained attention task, the verbal WM task reduced D2 receptor availability in the ventrolateral frontal cortex bilaterally and in the left medial temporal structures (amygdala, hippocampus), suggesting that dopamine release in these regions might have a specific role in WM. In addition, correlation analyses indicated that increased dopamine release in the right ventrolateral frontal cortex and the left ventral anterior cingulate during the WM task was associated with faster and more stable WM performance, respectively. Our results indicate that regionally specific components of the frontotemporal dopaminergic network are functionally involved in WM performance in humans.

Adult↗

PubMed2005

Naming of newly learned objects: a PET activation study.

The present study tracked the naming-related brain activity by positron emission tomography (PET) when successfully learned unfamiliar objects were named. Ten Finnish-speaking subjects participated in the study. Prior to the PET scan, each subject underwent a 4-day long training period in which 40 names of rare unfamiliar objects were taught. The stimulus categories were as follows: unfamiliar but real objects for which both the name and the definition were given during training, only the name was given, no information was given. In addition, familiar objects and visual noise patterns were used. The unfamiliar items mainly represented ancient domestic tools unknown to modern-day people. As semantic support did not affect the PET results, all trained items were pooled together. The trained objects vs. familiar objects contrast revealed rCBF increases in the left inferior frontal cortex (Broca's area), the left anterior temporal area, and the cerebellum. Likewise, the trained objects vs. unfamiliar objects (for which no information was given) contrast revealed more extensive left frontal (roughly Broca's area) and cerebellar rCBF increases, while anterior temporal activation was bilateral. Familiar objects, contrasted with both visual noise patterns and a rest condition, elicited activation increases in expected areas, i.e., bilateral occipital regions and the fusiform gyrus. Our results indicate that the naming of newly learned objects recruits more extensive brain areas than the naming of familiar items, namely a network that includes left-dominant frontotemporal areas and cerebellum. Its activity is tentatively related to enhanced lexical-semantic and lexical-phonological retrieval, as well as associative memory processes.

Aged↗

PubMed2005

Cortical 6-[18F]fluoro-L-dopa uptake and frontal cognitive functions in early Parkinson's disease.

Patients with Parkinson's disease (PD) have already at the early stages of the disease impaired performance especially in tests measuring frontal lobe functions such as attention. The pathophysiological basis of these deficits is unclear. In the present study, 21 non-demented, non-medicated patients at the early stage of PD and 24 healthy controls underwent a positron emission tomography (PET) scan with 6-[18F]fluoro-L-dopa (Fdopa) as the tracer. In addition, the PD patients performed a neuropsychological test battery, including a test measuring sustained attention (VIG) and a test requiring suppressed attention (Stroop). Both voxel-based Statistical Parametric Mapping (SPM) and automated region of interest (ROI) analysis were employed. Compared to controls, the PD patients had decreased Fdopa uptake in the striatum and a large cortical area of increased Fdopa uptake. The reaction time in the VIG test correlated positively with the Fdopa uptake of the dorsolateral prefrontal cortex and the performance in the Stroop test correlated negatively with the Fdopa uptake in an area including the medial frontal cortex and the anterior cingulate. The results show that cortical Fdopa uptake is increased in early non-medicated PD and suggest that the changes in frontal Fdopa uptake are related to cognitive impairments found in early PD.

Aging↗

PubMed2005

Binge drinking in midlife and dementia risk.

BACKGROUND: Studies examining the long-term effects of alcohol consumption on cognitive functioning have produced conflicting results. Our goal was to determine whether a long follow-up period combined with information about drinking patterns, in addition to total alcohol consumption, would provide new insights about the relationship of alcohol use with dementia risk. METHODS: A population-based cohort of 554 Finnish twins, who had provided data on alcohol consumption in questionnaires in 1975 and 1981, was followed for 25 years. Subjects were age 65 years or older at the time of dementia assessment in 1999-2001. Dementia risk was analyzed with respect to varying patterns of alcohol use by log-linear modeling, adjusted for age, sex, and education. RESULTS: By the end of follow-up, 103 participants had developed dementia. Binge drinking (ie, alcohol exceeding the amount of 5 bottles of beer or a bottle of wine on 1 occasion at least monthly), as reported in 1975, was associated with a relative risk of 3.2 (95% confidence interval=1.2-8.6) for dementia. Passing out at least twice as a result of excessive alcohol use during the previous year, as reported in 1981, was associated with a relative risk of 10.5 (2.4-46) for dementia in drinkers. CONCLUSIONS: Binge drinking in midlife is associated with an increased risk of dementia.

Aged↗

PubMed2004

Interaction between matrix metalloproteinase 3 and the epsilon4 allele of apolipoprotein E increases the risk of Alzheimer's disease in Finns.

Polymorphisms affecting the expression of matrix metalloproteinases (MMPs), i.e. proteolytic enzymes that degrade intercellular material, have been found at position -1607 (1G/2G) in MMP1 and at -1171 (5A/6A) in MMP3. Interestingly, elevated levels of MMP1 and MMP3 have been observed in the brains of Alzheimer's disease (AD) patients and those of tissue inhibitors of MMPs in the cerebrospinal fluid of AD and Parkinson's disease (PD) patients, suggesting a role for MMPs in these disorders. The aim was to investigate a possible association between the afore-mentioned MMP1 and MMP3 polymorphisms and the risk of developing AD or PD. The polymorphisms were genotyped in 97 AD, 52 PD and 101 control patients. We found an interaction between MMP3*5A and APOE 4 alleles (P < 0.0001) which increases the risk of AD (OR: 23.7, 95% CI: 5.8-144.9, P < 0.0001) compared to those who possess neither MMP3*5A nor APOE 4. In conclusion, our finding suggests that the MMP3 gene, especially together with APOE 4, may contribute to the development of AD.

Aged↗

PubMed2004

Neuropsychological functions in variant Alzheimer's disease with spastic paraparesis.

Few data exist on the effects of specific Alzheimer's disease (AD)-related mutations on cognitive function. We present neuropsychological test results in eight members of a large kindred with variant Alzheimer's disease (VarAD) due to a deletion of the presenilin 1 (PS-1) gene, encompassing exon 9. The disease was neuropathologically characterized by the presence of large, unusual, "cotton wool" plaques (CWP). Four surviving patients were prospectively tested, and retrospective neuropsychological data were collected from additional four deceased patients. The neuropsychological evaluation was based on tests of verbal and visual memory, abstract thinking, and visuoconstructive and spatial functions. In addition, psychiatric symptoms were evaluated. In four patients, brain glucose metabolism was examined by positron emission tomography (PET). PET showed temporoparietal hypometabolism typical of AD. In addition, variable patterns of hypometabolism (hemispherical asymmetry and occipital accentuation) were related to individual deficits of cognitive performance. However, all these early-onset patients (age range 43-63 years) with a deletion mutation of PS-1 gene showed prominent memory impairment and deficits in visuoconstructive and intellectual functions.

Alzheimer Disease↗

PubMed2004

Positron emission tomography examination of cerebral blood flow and glucose metabolism in young CADASIL patients.

BACKGROUND AND PURPOSE: CADASIL causes repeated ischemic strokes leading to subcortical vascular dementia. The purpose of this study was to assess whether cerebral blood flow (CBF) and regional cerebral metabolic rates of glucose (rCMR(gluc)) in CADASIL patients are affected in early adulthood. METHODS: CBF and rCMR(gluc) were examined with positron emission tomography in correlation with magnetic resonance imaging (MRI) in 14 adult (19 to 41 years) CADASIL patients with the Notch3 R133C mutation. Seven patients had experienced transient ischemic attack and 3 had experienced > or =1 strokes. RESULTS: The mean CBF in the CADASIL patients was significantly lower in both frontal (P=0.019) and occipital (P=0.009) white matter (WM) than those in the controls. CBF decreased significantly with increased severity of the disease. The patients had lower mean rCMR(gluc) values than the controls, although differences were not statistically significant. Sum scores of semiquantitative MRI rating scale (Scheltens) correlated significantly with WM CBF but not with rCMR(gluc). CONCLUSIONS: In CADASIL, there is an early and significant decrease in the CBF of WM associated with simultaneous MRI changes. These are obviously caused by the arteriopathy in long penetrating arteries and indicate early tissue damage, also expressed as impaired rCMR(gluc) in the WM.

Adult↗

PubMed2004

Dopaminergic effects of caffeine in the human striatum and thalamus.

Epidemiological studies have provided evidence that caffeine, an adenosine receptor antagonist, reduces the risk for Parkinson's disease. There are indications of specific interactions between striatal adenosine A(2A) and dopamine D(2) receptors, but the in vivo effects of caffeine on human dopamine system have not been investigated. In the present study, the dopaminergic effects of caffeine were examined with [(11)C]raclopride positron emission tomography (PET) in eight healthy habitual coffee drinkers after 24 h caffeine abstinence. Compared to oral placebo, 200 mg oral caffeine induced a 12% decrease in midline thalamic binding potential (p < 0.001). A trend-level increase in ventral striatal [(11)C]raclopride binding potential was seen with a correlation between caffeine-related arousal and putaminal dopamine D(2) receptor binding (r = -0.81, p = 0.03). The findings indicate that caffeine has effects on dopaminergic neurotransmission in the human brain, which may be differential in the striatum and the thalamus.

Adult↗

PubMed2004

Insular dopamine D2 receptors and novelty seeking personality in Parkinson's disease.

Novelty seeking is a temperament trait characterized by impulsiveness and exploratory behavior. Dopamine has been suggested to be the primary neurotransmitter modulator of novelty seeking, and in young healthy subjects, a correlation between increased novelty seeking and decreased insular cortical dopamine D2 receptor availability has been reported. The proposed link between dopamine deficiency and reduction in novelty seeking in Parkinson's disease is controversial. The present study examined whether a link between insular D2 receptor availability and novelty seeking can be replicated in Parkinson's disease patients. [11C]FLB 457 positron emission tomography imaging was carried out in 28 patients with Parkinson's disease, and the data were analyzed using voxel-based statistical analysis. The results demonstrated a negative correlation between the novelty seeking score and the dopamine D2 availability bilaterally in the insular cortex (corrected P=0.001; r=-0.74 [right hemisphere]; r=-0.66 [left hemisphere]). The results provide further support for a relationship between novelty seeking and insular D2 receptors. They indicate that the association is cross-cultural, independent of age, and unaffected by dopaminergic degeneration.

Aged↗

PubMed2004

Visual object recognition deficits in early Parkinson's disease.

The nature of the visual perception deficits in Parkinson's disease (PD) has remained unclear. The present study explored whether there emerge deficits in the different stages of visual object recognition in early PD. Twenty-eight patients and 14 healthy controls were studied. A set of reaction time tasks were applied to measure the different stages of object recognition. The results indicate some selective problems in both basic perceptual and semantic visual processing at an early stage of cognitive deterioration in PD.

Aged↗

PubMed2004

Expectation of caffeine induces dopaminergic responses in humans.

Recent neuroimaging studies indicate that placebo treatments can induce clinically relevant neurobiological responses in patients with Parkinson's disease, depression and pain. The present study aimed to investigate neurotransmitter function in psychostimulant expectation, with the focus on dopaminergic effects of placebo caffeine in healthy human subjects. Eight habitual coffee drinkers were examined twice with [11C]raclopride positron emission tomography after no treatment and after oral placebo tablets in a counter-balanced setting. During the placebo condition the subjects were instructed that they had a 50% chance of receiving caffeine, but all received placebo. As compared with no treatment, placebo induced a significant bilateral dopamine release in the thalamus, as reflected by a 15% reduction in thalamic [11C]raclopride binding (P < 0.001). The level of arousal after placebo correlated positively with the tracer binding in the putamen (r = -0.91, P = 0.004). The results indicate that caffeine expectation induces dopaminergic placebo effects, and that these effects are similar to previous findings with oral caffeine. The results therefore suggest that caffeine and placebo caffeine may share some dopaminergic mechanisms of action.

Adult↗