Kognitiiviset ongelmat ovat yleisiä Parkinsonin taudissa

• Parkinsonin taudissa kognitiivisia ongelmia voi ilmetä jo alkuvaiheissa. • Voimakkaimmin heikentyvät tarkkaavuus, hahmottaminen ja toiminnanohjaus. • Kognitiivisen heikentymän riskiä ennustavat erityisesti vaikeampi motorinen oireisto, ikä, miessukupuoli sekä ei-motoristen oireiden laajuus. • Patologinen tausta liittyy sekä alfasynukleiinin kertymään, välittäjäainejärjestelmien muutoksiin että osin amyloidin kertymään. • Parkinsonin taudin muistisairauden hoidon kulmakivi on asetyylikoliiniesteraasin estäjälääkitys.</p

Bupropion Causes Misdiagnosis in Brain Dopamine Transporter Imaging for Parkinsonism

Objective: The objective of this study was to report long-lasting effects of bupropion on brain dopamine transporter (DAT) in a patient with depression and parkinsonism. Methods: The patient was a 52-year old man who had been treated with 150 mg/d of bupropion for depression. The patient developed cognitive problems, bradykinesia, and reduced stride length for which he was scanned with [123I]FP-CIT single photon emission computed tomography after the recommended 1-week discontinuation of bupropion. Levodopa treatment trial was initiated without a response. Eleven months later, the patient was scanned for a second time after a 1-month stoppage of bupropion. Results: The first scan was abnormal with left putamen specific binding ratio of 1.99 (SDs from the reference value mean, −2.40), right putamen of 2.27 (SD, −1.84), left caudate of 2.33 (SD, −2.26), and right caudate of 2.29 (SD, −2.18). The second scan (after 1-month discontinuation) was normal, and specific binding ratios had increased from 5.2% to 31.7% in all striatal regions as compared with the first scan. Brain magnetic resonance imaging and [18F]fluorodeoxyglucose positron emission tomography imaging were normal, and there was no levodopa response or other features supporting neurodegenerative parkinsonism. Conclusions: Bupropion has previously generally been discontinued 1 week prior DAT imaging, which meets the recommended, albeit arbitrary, time interval of 5 plasma clearance half-lives before the scan. One-week discontinuation of bupropion before DAT imaging may be insufficiently short. Our case shows that longer medication washout and rescan may be needed when there is contradiction between the imaging result and clinical outcome in patients with medications affecting DAT binding</p

Association of Peripheral Insulin Resistance and Other Markers of Type 2 Diabetes Mellitus with Brain Amyloid Deposition in Healthy Individuals at Risk of Dementia

We explored the association of type 2 diabetes related blood markers with brain amyloid accumulation on PiB-PET scans in 41 participants from the FINGER PET sub-study. We built logistic regression models for brain amyloid status with12 plasma markers of glucose and lipid metabolism, controlled for diabetes and APOE epsilon 4 carrier status. Lower levels of insulin, insulin resistance index (HOMA-IR), C-peptide, and plasminogen activator (PAI-1) were associated with amyloid positive status, although the results were not significant after adjusting for multiple testing. None of the models found evidence for associations between amyloid status and fasting glucose or HbA1c.Peer reviewe

Virkeänä ratissa : Käsikirja

Käsikirjaan on koottu tietoa, vinkkejä ja toimintamalleja, joita on kehitetty yhdessä eri vaikuttajatahojen kanssa

The Impact of Bdnf Gene Deficiency to the Memory Impairment and Brain Pathology of APPswe/PS1dE9 Mouse Model of Alzheimer's Disease

Peer reviewe

Associations of CAIDE Dementia Risk Score with MRI, PIB-PET measures, and cognition

Background: CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile. Objectives: This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures. Methods: FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation. Results: Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (beta- coefficient -0.29, p = 0.001) and hippocampal volume (beta- coefficient -0.28, p = 0.003), lower cortical thickness (beta-coefficient -0.19, p = 0.042), and poorer cognition (beta-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p <0.001). Higher CAIDE Dementia Risk Score including APOE genotype was additionally related to more pronounced MTA (OR 1.15,95% CI 1.00-1.30). No associations were found with periventricular WML or amyloid accumulation. Conclusions: The CAIDE Dementia Risk Score was related to indicators of cerebrovascular changes and neurodegeneration on MRI, and cognition. The lack of association with brain amyloid accumulation needs to be verified in studies with larger sample sizes.Peer reviewe

Wintertime subarctic new particle formation from Kola Peninsula sulfur emissions

The metallurgical industry in the Kola Peninsula, north-west Russia, form, after Norilsk, Siberia, the second largest source of air pollution in the Arctic and subarctic domain. Sulfur dioxide (SO2/emissions from the ore smelters are transported to wide areas, including Finnish Lapland. We performed investigations on concentrations of SO2, aerosol precursor vapours, aerosol and ion cluster size distributions together with chemical composition measurements of freshly formed clusters at the SMEAR I station in Finnish Lapland relatively close (similar to 300 km) to the Kola Peninsula industrial sites during the winter 2019-2020. We show that highly concentrated SO2 from smelter emissions is converted to sulfuric acid (H2SO4/in sufficient concentrations to drive new particle formation hundreds of kilometres downwind from the emission sources, even at very low solar radiation intensities. Observed new particle formation is primarily initiated by H2SO4-ammonia (negative-)ion-induced nucleation. Particle growth to cloud condensation nuclei (CCN) sizes was concluded to result from sulfuric acid condensation. However, air mass advection had a large role in modifying aerosol size distributions, and other growth mechanisms and condensation of other compounds cannot be fully excluded. Our results demonstrate the dominance of SO2 emissions in controlling wintertime aerosol and CCN concentrations in the subarctic region with a heavily polluting industry.Peer reviewe

White Matter Changes on Diffusion Tensor Imaging in the FINGER Randomized Controlled Trial

Background: Early pathological changes in white matter microstructure can be studied using the diffusion tensor imaging (DTI). It is not only important to study these subtle pathological changes leading to cognitive decline, but also to ascertain how an intervention would impact the white matter microstructure and cognition in persons at-risk of dementia.Objectives: To study the impact of a multidomain lifestyle intervention on white matter and cognitive changes during the 2-year Finnish Geriatric Intervention Study to prevent Cognitive Impairment and Disability (FINGER), a randomized controlled trial in at-risk older individuals (age 60-77 years) from the general population.Methods: This exploratory study consisted of a subsample of 60 FINGER participants. Participants were randomized to either a multidomain intervention (diet, exercise, cognitive training, and vascular risk management, n = 34) or control group (general health advice, n = 26). All underwent baseline and 2-year brain DTI. Changes in fractional anisotropy (FA), diffusivity along domain (F1) and non-domain (F2) diffusion orientations, mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and their correlations with cognitive changes during the 2-year multidomain intervention were analyzed.Results: FA decreased, and cognition improved more in the intervention group compared to the control group (p < 0.05), with no significant intergroup differences for changes in F1, F2, MD, AxD, or RD. The cognitive changes were significantly positively related to FA change, and negatively related to RD change in the control group, but not in the intervention group.Conclusion: The 2-year multidomain FINGER intervention may modulate white matter microstructural alterations

27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial

Background: 27-Hydroxycholesterol (27-OH), the main circulating oxysterol in humans and the potential missing link between peripheral hypercholesterolemia and Alzheimer's disease (AD), has not been investigated previously in relation to cognition and neuroimaging markers in the context of preventive interventions.Methods: The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older individuals (60-77 years) at increased risk for dementia but without dementia or substantial cognitive impairment from the general population. Participants were randomized to a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice) in a 1:1 ratio. Outcome assessors were masked to group allocation. This FINGER exploratory sub-study included 47 participants with measures of 27-OH, cognition, brain MRI, brain FDG-PET, and PiB-PET. Linear regression models were used to assess the cross-sectional and longitudinal associations between 27-OH, cognition, and neuroimaging markers, considering several potential confounders/intervention effect modifiers.Results: 27-OH reduction during the intervention was associated with improvement in cognition (especially memory). This was not observed in the control group. The intervention reduced 27-OH particularly in individuals with the highest 27-OH levels and younger age. No associations were found between changes in 27-OH levels and neuroimaging markers. However, at baseline, a higher 27-OH was associated with lower total gray matter and hippocampal volume, and lower cognitive scores. These associations were unaffected by total cholesterol levels. While sex seemed to influence associations at baseline, it did not affect longitudinal associations.Conclusion: 27-OH appears to be a marker not only for dementia/AD risk, but also for monitoring the effects of preventive interventions on cholesterol metabolism