Mikkeli Osteoporosis Index Identifies Fracture Risk Factors and Osteoporosis and Intervention Thresholds Parallel with FRAX

Osteoporosis Index (MOI) was developed from Fracture Index (FI), a validated fracture risk score, to identify also osteoporosis. MOI risk factors are age, weight, previous fracture, family history of hip fracture or spinal osteoporosis, smoking, shortening of the stature, and use of arms to rise from a chair. The association of these risk factors with BMD was examined in development cohorts of 300 Finnish postmenopausal women with a fracture and in a population control of 434 women aged 65–72. Validation cohorts included 200 fracture patients and a population control of 943 women aged 58–69. MOI identified femoral neck osteoporosis in these cohorts as well as the Osteoporosis Self-Assessment Tool (OST). In the pooled fracture cohort, the association of BMI-based FRAX fracture risk with MOI was good. After BMD measurement, MOI identified well FRAX hip fracture risk-based Intervention Thresholds (ITs) (AUC 0.74–0.90)

Long-term antipsychotic and benzodiazepine use. and brain volume changes in schizophrenia : The Northern Finland Birth Cohort 1966 study

High doses of antipsychotics have been associated with loss in cortical and total gray matter in schizophrenia. However, previous imaging studies have not taken benzodiazepine use into account, in spite of evidence suggesting adverse effects such as cognitive impairment and increased mortality. In this Northern Finland Birth Cohort 1966 study, 69 controls and 38 individuals with schizophrenia underwent brain MRI at the ages of 34 and 43 years. At baseline, the average illness duration was over 10 years. Brain structures were delineated using an automated volumetry system, volBrain, and medication data on cumulative antipsychotic and benzodiazepine doses were collected using medical records and interviews. We used linear regression with intracranial volume and sex as covariates; illness severity was also taken into account. Though both medication doses associated to volumetric changes in subcortical structures, after adjusting for each other and the average PANSS total score, higher scan-interval antipsychotic dose associated only to volume increase in lateral ventricles and higher benzodiazepine dose associated with volume decrease in the caudate nucleus. To our knowledge, there are no previous studies reporting associations between benzodiazepine dose and brain structural changes. Further studies should focus on how these observations correspond to cognition and functioning.Peer reviewe

Spontaneous blood oxygen fluctuation in awake and sedated brain cortex – a BOLD fMRI study

Abstract Functional magnetic resonance imaging (fMRI) has become a leading tool in the evaluation of the human brain function. In fMRI the activation induced blood oxygenation changes in the brain can be detected with an inherent blood oxygen level dependent (BOLD) contrast. Even small blood oxygen fluctuations in a resting brain can be depicted with the BOLD contrast. This thesis focuses on characterizing spontaneous oxygenation fluctuations of the brain by using BOLD fMRI. The effects of anesthetics on blood oxygen fluctuations were assessed in 38 children and 12 adults. The spatial distribution, frequency, synchrony, and statistical independence of the spontaneous oxygenation changes were analyzed. The role of imaging artifacts in the generation of BOLD signal fluctuations was investigated. The study aimed to develop and compare methods of detecting the nondeterministic oxygenation fluctuations of the brain. VLF BOLD signal fluctuation in the brain cortex is induced by physiological oscillation instead of imaging artifacts. This study shows for the first time how the power and synchrony of very low frequency (VLF <  0.05 Hz) blood oxygen fluctuation significantly increases after sedation. In deeper anesthesia, the VLF fluctuation overpowers other sources of blood oxygen variation as a sign of reduced blood flow and altered hemodynamic control. Regional hemodynamic mechanisms induce non-Gaussian features on the VLF blood oxygen fluctuation that can be depicted effectively with independent component analysis. Combined use of frequency, time, and spatial domain analysis guarantees a more complete picture of brain oxygenation fluctuations. The results of this thesis have a dualistic impact on fMRI research. First of all, VLF fluctuation alters the BOLD activation and connectivity results after sedation. Thus it has to be accounted for in the fMRI of sedated subjects. Secondly, by using the methods developed in this thesis, VLF fluctuation and other physiological BOLD signal sources can now be used in characterizing physiological alterations and pathology of the brain

Fractional amplitude of physiological fluctuations of resting state fNIRS in Alzheimer’s disease patient and healthy control

Abstract Functional magnetic resonance imaging (fMRI) is a common medical device to diagnose Alzheimer’s disease (AD), but it is not for all subjects due to its cost and other issues. We investigated the potential of functional near-infrared spectroscopy (fNIRS) to separate AD patients from controls as a pre-screening prior to more thorough examination using fMRI. For this purpose, two-channel fNIRS device with 690 nm and 830 nm, sampled at 10 Hz, was placed on the forehead with 3 cm distance between light source and detector to provide resting state fNIRS signals from both sides of pre-frontal cortex. We applied fractional amplitude of physiological fluctuation (fAPF), modified from fractional amplitude of low frequency fluctuation (fALFF), to oxy-, deoxy-, and total-hemoglobin in very low frequency (0.008‐0.1 Hz), respiratory (0.1‐0.6 Hz), and cardiac (0.6‐5 Hz) bands. A t-test at 0.05 significance level was used to evaluate if the fAPF score from AD patients and healthy controls is significantly different. We found that fAPF score of total hemoglobin from both side at cardiac band showed its potential to distinguish AD patients from healthy controls. This finding was in-line with the recent finding that heart failure may co-occur in AD patients with the prevalence of one third of cases

Inverse correlation of fluctuations of cerebral blood and water concentrations in humans

Abstract Near-infrared spectroscopy (fNIRS) measures concentrations of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in the brain. Recently, we demonstrated its potential also for measuring concentrations of cerebral water (cH₂O). We performed fNIRS measurements during rest to study fluctuations in concentrations of cH₂O, HbO and HbR in 33 well-rested healthy control subjects (HC) and 18 acutely sleep-deprived HC. Resting-state fNIRS signal was filtered in full-band, cardiac, respiratory, low-, and very-low-frequency bands. The sum of HbO and HbR constitutes the regional cerebral blood volume (CBV). CBV and cH₂O concentrations were analyzed via temporal correlation and phase synchrony. Fluctuation in concentrations of cH₂O and CBV was strongly anti-correlated across all frequency bands in both frontal and parietal cortices. Fluctuation in concentrations of cH₂O and CBV showed neither a completely synchronous nor a random phase relationship in both frontal and parietal cortices. Acutely sleep-deprived subjects did not show significant differences in temporal correlation or phase synchrony between fluctuations in cH₂O and CBV concentrations compared with well-rested HC. The reciprocal interrelation between fluctuations in CBV and cH₂O concentrations is consistent with the Munro–Kellie doctrine of constant intracranial volume. This coupling may constitute a functional mechanism underlying glymphatic circulation, which persists despite acutely disturbed sleep patterns

Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy

Abstract Background: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls. Methods: In this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis. Results: We find that variance and fractional variance in the very low frequency (MREGvlf) band are greater in NT1 compared to HC, while cardiac (MREGcard) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREGvlf shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREGcard variance (R = −0.48, p = 0.0249). Conclusions: We suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1

Glymfaattinen järjestelmä avaa aivojen padot

Tiivistelmä Glymfaattinen (glia-lymfaattinen) järjestelmä eli glianestekierto on aivojen perivaskulaarinen puhdistusjärjestelmä, joka toimii syvän unen ja anestesian aikana ja mahdollistaa aivo-selkäydinnesteen virtauksen aivokudokseen huuhtomaan valveen aikana kertyneitä aineenvaihduntatuotteita. Aivo-selkäydinneste sukeltaa aivoihin valtimoita ympäröivissä perivaskulaaritiloissa ja pääsee aivokudokseen perivaskulaaritiloja ympäröivien astrosyyttien akvaporiini 4 (AQP4) -vesikanavien avustamana. Aivokudoksessa solunulkoinen neste ja sen sisältämät aineenvaihduntatuotteet, kuten beeta-amyloidi, sekoittuvat aivo-selkäydinnesteeseen. Tämä neste poistuu aivojen soluvälitilasta laskimoiden perivaskulaaritilojen kautta käyttämällä useita ulosvirtausreittejä, muun muassa aivokalvojen imusuonia. Glymfaattisen järjestelmän puutteellisen toiminnan arvellaan altistavan aivojen rappeumasairauksille sekä heikentävän toipumista aivoverenkiertohäiriöstä tai aivovammasta. Järjestelmän toimintaa tehostamalla voitaisiin puolestaan ehkäistä aivojen rappeumasairauksia tai edesauttaa esimerkiksi lääkkeiden pääsyä keskushermostoon. Glymfaattinen järjestelmä kuvattiin ensin koe-eläintutkimuksissa, ja ihmisen vastaavasta järjestelmästä tarvitaan vielä lisää tutkimusnäyttöä.Abstract The glymphatic (glial-lymphatic) system is mainly active during deep sleep and anesthesia, and allows the passage of cerebrospinal fluid into the brain parenchyma to wash the brain of harmful endogenous metabolic waste. Cerebrospinal fluid flows from the subarachnoid space to the periarterial spaces, and enters the brain parenchyma facilitated by astrocytic aquaporin 4 (AQP4) water channels. In the brain parenchyma, metabolic waste products in the interstitial fluid mix with the cerebrospinal fluid. This solute-containing fluid then flows to the perivenous spaces and is drained from the brain through several efflux routes, including the meningeal lymphatic vessels. Impaired glymphatic flow may contribute to the pathogenesis of several chronic neurodegenerative diseases and poor recovery from traumatic brain injury and ischemic stroke. On the other hand, enhancing glymphatic flow might help to prevent neurodegenerative diseases or facilitate drug delivery to the central nervous system. Although the glymphatic system was first described in rodents, recent studies suggest that a similar system functions in the human brain

Multimodal brain imaging with magnetoencephalography:a method for measuring blood pressure and cardiorespiratory oscillations

Abstract Studies with magnetoencephalography (MEG) are still quite rarely combined simultaneously with methods that can provide a metabolic dimension to MEG investigations. In addition, continuous blood pressure measurements which comply with MEG compatibility requirements are lacking. For instance, by combining methods reflecting neurovascular status one could obtain more information on low frequency fluctuations that have recently gained increasing interest as a mediator of functional connectivity within brain networks. This paper presents a multimodal brain imaging setup, capable to non-invasively and continuously measure cerebral hemodynamic, cardiorespiratory and blood pressure oscillations simultaneously with MEG. In the setup, all methods apart from MEG rely on the use of fibre optics. In particular, we present a method for measuring of blood pressure and cardiorespiratory oscillations continuously with MEG. The potential of this type of multimodal setup for brain research is demonstrated by our preliminary studies on human, showing effects of mild hypercapnia, gathered simultaneously with the presented modalities