Intrinsic and task based interactions between structural and functional connectivity in midlife : implications for age-related brain vulnerability.

The proportion of older adults is increasing as people live longer, projecting a financial burden on society because of retirement and care costs. Cognitive functioning is a critical factor in functional independence and quality of life in older age. Although several theories explaining the relationship between brain aging and cognitive decline have been proposed, a unified understanding is lacking. The overarching goal of the current dissertation was to better characterize age related brain and cognitive changes in midlife in order to identify targets for future interventions. Midlife likely offers an optimal time for interventions that prevent or delay cognitive decline before an overwhelming accumulation of pathology. The three Aims of the dissertation used a large sample of middle-aged adults with neuropsychological testing, a metabolic health assessment, and multimodal magnetic resonance imaging. Together, the Aims identified age related changes in the brain, the effects on cognitive functioning, and examined potential mechanisms. Aim #1 reported that white matter structure was associated with network efficiency among the default mode and frontoparietal networks. Aim #2 reported that age was associated with a failure to inhibit the default mode network during an executive function task that required low cognitive demand. However, on a more challenging condition, age was associated with lower frontoparietal network activity. Better performance on the challenging condition was associated with lower default mode network activity and higher frontoparietal network activity. Aim #3 reported that metabolic syndrome did not accelerated age-related brain changes identified in Aim #2. The results challenge existing theories regarding the effect of age on the relationship between the brain and cognition. New lines of inquiry regarding the role of metabolic syndrome in typical aging are suggested. Lastly, the results present exciting implications for several potential interventions to prevent cognitive decline.Psycholog

CSF T-Tau/Aβ42 Predicts White Matter Microstructure in Healthy Adults at Risk for Alzheimer’s Disease

Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ42 are linked with Alzheimer’s disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ42, total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ42 were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ42 levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter

Maternal prepregnancy body mass index and offspring white matter microstructure: results from three birth cohorts

Prepregnancy maternal obesity is a global health problem and has been associated with offspring metabolic and mental ill-health. However, there is a knowledge gap in understanding potential neurobiological factors related to these associations. This study explored the relation between maternal prepregnancy body mass index (BMI) and offspring brain white matter microstructure at the age of 6, 10, and 26 years in three independent cohorts. Maternal BMI was associated with higher FA and lower MD in multiple brain tracts in offspring aged 10 and 26 years, but not at 6 years of age. Future studies should examine whether our observations can be replicated and explore the potential causal nature of the findings.This work was supported by the European Union’s Horizon 2020 research and innovation program [grant agreement no. 633595 DynaHEALTH] and no. 733206 LifeCycle], the Netherlands Organization for Health Research and Development [ZONMW Vici project 016.VICI.170.200]. The PREOBE cohort was funded by Spanish Ministry of Innovation and Science. Junta de Andalucía: Excellence Projects (P06-CTS-02341) and Spanish Ministry of Economy and Competitiveness (BFU2012-40254-C03-01). The first phase of the Generation R Study is made possible by financial support from the Erasmus Medical Centre, the Erasmus University, and the Netherlands Organization for Health Research and Development (ZonMW, grant ZonMW Geestkracht 10.000.1003). The Northern Finland Birth Cohort 1986 is funded by University of Oulu, University Hospital of Oulu, Academy of Finland (EGEA), Sigrid Juselius Foundation, European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643), NIH/NIMH (5R01MH63706:02

Effects of Ethanol and NAP on Cerebellar Expression of the Neural Cell Adhesion Molecule L1

The neural cell adhesion molecule L1 is critical for brain development and plays a role in learning and memory in the adult. Ethanol inhibits L1-mediated cell adhesion and neurite outgrowth in cerebellar granule neurons (CGNs), and these actions might underlie the cerebellar dysmorphology of fetal alcohol spectrum disorders. The peptide NAP potently blocks ethanol inhibition of L1 adhesion and prevents ethanol teratogenesis. We used quantitative RT-PCR and Western blotting of extracts of cerebellar slices, CGNs, and astrocytes from postnatal day 7 (PD7) rats to investigate whether ethanol and NAP act in part by regulating the expression of L1. Treatment of cerebellar slices with 20 mM ethanol, 10−12 M NAP, or both for 4 hours, 24 hours, and 10 days did not significantly affect L1 mRNA and protein levels. Similar treatment for 4 or 24 hours did not regulate L1 expression in primary cultures of CGNs and astrocytes, the predominant cerebellar cell types. Because ethanol also damages the adult cerebellum, we studied the effects of chronic ethanol exposure in adult rats. One year of binge drinking did not alter L1 gene and protein expression in extracts from whole cerebellum. Thus, ethanol does not alter L1 expression in the developing or adult cerebellum; more likely, ethanol disrupts L1 function by modifying its conformation and signaling. Likewise, NAP antagonizes the actions of ethanol without altering L1 expression

Regional white matter hyperintensities: aging, Alzheimer's disease risk, and cognitive function

Latar belakang perubahan berat badan merupakan salah satu efek samping yang sering dikeluhkan oleh akseptor KB implan, suntik, maupun pil.Kenaikan berat badan yang dialami oleh akseptor KB hormonal dipengaruhi oleh kadar Hormon Estrogen dan Progesteron yang terkandung didalam komponen KB hormonal. Tujuan untuk mengetahui variasi perubahan berat badan akseptor KB Implan, Suntik dan Pil. Metode Penelitian yaitu survey deskriptif.Teknik pengambilan sampel adal puerposive sampling berjumlah 62 responden. Hasil dari 62 responden akseptor KB sejumlah 48 orang (77,4%) mengalami peningkatan berat badan, 8 orang (12,9%) mengalami penurunan berat badan dan 6 orang (9,7%) tidak mengalami perubahan berat badan. Simpulan keseluruhan akseptor KB implan suntik maupun pil mengalami perubahan berat badan sebelum dan sesudah pemakaian alat kontrasepsi tersebut.Saran disarankan kepada bidan ataupun tenaga kesehatan untuk meningkatkan pelayanan tentang alat kontrasepsi baik keuntungan mapun kerugian dari alat kontrasepsi tersebut