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Neurobiology of Aging

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https://www.readbyqxmd.com/read/29870951/association-of-telomere-length-with-general-cognitive-trajectories-a-meta-analysis-of-four-prospective-cohort-studies
#1
Yiqiang Zhan, Mark S Clements, Rosebud O Roberts, Maria Vassilaki, Brooke R Druliner, Lisa A Boardman, Ronald C Petersen, Chandra A Reynolds, Nancy L Pedersen, Sara Hägg
To investigate the association of telomere length (TL) with trajectories of general cognitive abilities, we used data on 5955 participants from the Sex Differences in Health and Aging Study and the Swedish Adoption/Twin Study of Aging in Sweden, and the Mayo Clinic Study of Aging, and the Health and Retirement Study in the United States. TL was measured at baseline, while general cognitive ability was assessed repeatedly up to 7 occasions. Latent growth curve models were used to examine the associations. One standard deviation increase of TL was associated with 0...
June 2, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29866399/clinical-features-and-genetic-characterization-of-two-dizygotic-twins-with-c9orf72-expansion
#2
Francesca Luisa Conforti, Rosanna Tortelli, Giovanna Morello, Rosa Capozzo, Maria Rosaria Barulli, Sebastiano Cavallaro, Giancarlo Logroscino
The objective of the study was to present a detailed clinical, genetic, and epigenetic characterization of 2 amyotrophic lateral sclerosis (ALS) concordant dizygotic twins. The described cases underwent clinical and paraclinical examinations according to the motor neuron disease protocol of our referral center. Mutation analysis of the major causative genes related to ALS was performed. The methylation profile of the CpG island located in the promoter region of C9orf72 and in the repeat region itself was investigated by bisulfite sequencing of C9orf72 expansion carriers...
June 1, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29864717/levels-of-retinal-iapp-are-altered-in-alzheimer-s-disease-patients-and-correlate-with-vascular-changes-and-hippocampal-iapp-levels
#3
Nina Schultz, Elin Byman, Malin Wennström
Islet amyloid polypeptide (IAPP) forms toxic aggregates in the brain of patients with Alzheimer's disease (AD). Whether IAPP also affects the retina in these patients is still unknown. Levels of IAPP in soluble and insoluble homogenate fractions of retina and hippocampus from AD patients and nondemented controls were analyzed using ELISA. Number of pericytes and vessel length were determined by analysis of immunostained retina and hippocampus. Insoluble retinal fractions of AD patients contained lower levels of unmodified IAPP, whereas soluble retinal fractions contained increased levels of the same...
June 1, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29864716/a-simple-and-clinically-relevant-combination-of-neuroimaging-and-functional-indexes-for-the-identification-of-those-at-highest-risk-of-alzheimer-s-disease
#4
Hossein Tabatabaei-Jafari, Erin Walsh, Marnie E Shaw, Nicolas Cherbuin
The current challenge in clinical practice is to identify those with mild cognitive impairment (MCI), who are at greater risk of Alzheimer's disease (AD) conversion in the near future. The aim of this study was to assess a clinically practical new hippocampal index-hippocampal volume normalized by cerebellar volume (hippocampus to cerebellum volume ratio) used alone or in combination with scores on the Mini-Mental State Examination, as a predictor of conversion from MCI to AD. The predictive value of the HCCR was also contrasted to that of the hippocampal volume to intracranial volume ratio...
June 1, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29859364/do-diurnal-cortisol-levels-mediate-the-association-between-sleep-disturbances-and-cognitive-impairment
#5
José Haba-Rubio, Sami Ouanes, Yannick Franc, Pedro Marques-Vidal, Gerard Waeber, Peter Vollenweider, Armin von Gunten, Martin Preisig, Christine Kuehner, Enrique Castelao, Raphaël Heinzer, Julius Popp
Previous research found an association between sleep disturbances and cognitive deficits on the one hand, and between increased cortisol levels and poor cognitive performance on the other hand. We hypothesized that cortisol may, at least partially, mediate the link between sleep disturbances and cognitive impairment (CI). We analyzed data from 440 nondemented subjects aged ≥65 years (72.4 ± 4.5 years old, 55.7% women) participating at the population-based CoLaus/PsyCoLaus study, who underwent cognitive evaluation, complete polysomnography and cortisol measures during the day...
May 30, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29909181/stress-related-deficits-of-older-adults-spatial-working-memory-an-eeg-investigation-of-occipital-alpha-and-frontal-midline-theta-activities
#6
Amanda C Marshall, Nicholas Cooper, Livia Rosu, Steffan Kennett
Studies highlight cumulative life stress as a significant predictor of accelerated cognitive aging. This study paired electrophysiological with behavioral measures to explore how cumulative stress affects attentional and maintenance processes underpinning working memory retention. We collected electroencephalographic recordings from 60 individuals (30 older, 30 younger) reporting high or low levels of cumulative stress during the performance of a spatial Sternberg task. We measured mid-occipital alpha (8-12 Hz) and frontal-midline theta (4-6 Hz) as indicators of attentional and maintenance processes...
May 29, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29909180/parkinsonism-is-associated-with-altered-primary-motor-cortex-plasticity-in-frontotemporal-dementia-primary-progressive-aphasia-variant
#7
Flavio Di Stasio, Suppa Antonio, Fabbrini Andrea, Marsili Luca, Asci Francesco, Conte Antonella, Trebbastoni Alessandro, De Lena Carlo, Berardelli Alfredo
In frontotemporal dementia (FTD), the behavioral variant (bv-FTD) and nonfluent variant of primary progressive aphasia (nfv-PPA) reflect a prominent neurodegenerative involvement of the frontal lobe networks, which may include the premotor and motor areas and thus cause heterogeneous clinical symptoms including parkinsonism. With the technique of transcranial magnetic stimulation, we investigated long-term potentiation- and long-term depression-like plasticity in the primary motor cortex of bv-FTD and nfv-PPA patients, with and without parkinsonism, by using the theta-burst stimulation (TBS) protocol...
May 29, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29909179/apoe-%C3%AE%C2%B54-status-in-healthy-older-african-americans-is-associated-with-deficits-in-pattern-separation-and-hippocampal-hyperactivation
#8
Neha Sinha, Chelsie N Berg, Nicholas J Tustison, Ashlee Shaw, Diane Hill, Michael A Yassa, Mark A Gluck
African Americans are 1.4 times more likely than European Americans to carry the apolipoprotein E (APOE) ε4 allele, a risk factor for Alzheimer's disease (AD). However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to genetic risk for AD. In particular, no past study on African Americans has examined the effect of APOE ε4 status on pattern separation-mnemonic discrimination performance and its corresponding neural computations in the hippocampus...
May 26, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29909144/pde8b-mutation-is-not-associated-with-parkinson-s-disease-in-a-taiwanese-population
#9
Tian-Sin Fan, Ruey-Meei Wu, Han-I Lin, Chieh Cheng, Chin-Hsien Lin
Mutations in the phosphodiesterase 8B gene (PDE8B) were recently linked to autosomal-dominant striatal degeneration clinically presenting as slowly progressive parkinsonism. PDE8B degrades cyclic adenosine monophosphate (cAMP), a second messenger involved in dopamine signaling. Dopamine deficiency is the pathognomonic feature of Parkinson's disease (PD). Few studies have explored the role of PDE8B in PD. We aim to address the genetic contribution of PDE8B in early-onset and familial PD in a Taiwanese population...
May 26, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29908415/curvilinear-locus-coeruleus-functional-connectivity-trajectories-over-the-adult-lifespan-a-7t-mri-study
#10
Heidi I L Jacobs, Lisa Müller-Ehrenberg, Nikos Priovoulos, Alard Roebroeck
The locus coeruleus (LC) plays a crucial role in modulating several higher order cognitive functions via its widespread projections to the entire brain. We set out to investigate the hypothesis that LC functional connectivity (FC) may fluctuate nonlinearly with age and explored its relation to memory function. To that end, 49 cognitively healthy individuals (19-74 years) underwent ultra high-resolution 7T resting-state functional magnetic resonance imaging and cognitive testing. FC patterns from the LC to regions of the isodendritic core network and cortical regions were examined using region of interest-to-region of interest analyses...
May 24, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29908416/postmortem-brain-mri-is-related-to-cognitive-decline-independent-of-cerebral-vessel-disease-in-older-adults
#11
Robert J Dawe, Lei Yu, Julie A Schneider, Konstantinos Arfanakis, David A Bennett, Patricia A Boyle
The purpose of this study was to determine whether metrics of brain tissue integrity derived from postmortem magnetic resonance imaging (MRI) are associated with late-life cognitive decline, independent of cerebral vessel disease. Using data from 554 older adults, we used voxelwise regression to identify regions where the postmortem MRI transverse relaxation rate constant R2 was associated with the rate of decline in global cognition. We then used linear mixed models to investigate the association between a composite R2 measure and cognitive decline, controlling for neuropathology including 3 indices of vessel disease: atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy...
May 23, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29886022/no-supportive-evidence-for-tia1-gene-mutations-in-a-european-cohort-of-als-ftd-spectrum-patients
#12
Yalda Baradaran-Heravi, Lubina Dillen, Hung Phuoc Nguyen, Sara Van Mossevelde, Jonathan Baets, Peter De Jonghe, Sebastiaan Engelborghs, Peter P De Deyn, Mathieu Vandenbulcke, Rik Vandenberghe, Philip Van Damme, Patrick Cras, Eric Salmon, Matthis Synofzik, Peter Heutink, Carlo Wilke, Javier Simon-Sanchez, Ricard Rojas-Garcia, Janina Turon-Sans, Alberto Lleó, Ignacio Illán-Gala, Jordi Clarimón, Barbara Borroni, Alessandro Padovani, Pau Pastor, Monica Diez-Fairen, Miquel Aguilar, Ellen Gelpi, Raquel Sanchez-Valle, Sergi Borrego-Ecija, Radoslav Matej, Eva Parobkova, Benedetta Nacmias, Sandro Sorbi, Silvia Bagnoli, Alexandre de Mendonça, Catarina Ferreira, Matthew J Fraidakis, Janine Diehl-Schmid, Panagiotis Alexopoulos, Maria Rosário Almeida, Isabel Santana, Christine Van Broeckhoven, Julie van der Zee
We evaluated the genetic contribution of the T cell-restricted intracellular antigen-1 gene (TIA1) in a European cohort of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) patients. Exonic resequencing of TIA1 in 1120 patients (693 FTD, 341 ALS, 86 FTD-ALS) and 1039 controls identified in total 5 rare heterozygous missense variants, affecting the TIA1 low-complexity domain (LCD). Only 1 missense variant, p.Met290Thr, identified in a familial FTD patient with disease onset at 64 years, was absent from controls yet received a combined annotation-dependent depletion score of 11...
May 23, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29909178/the-effect-of-apoe-genotype-on-alzheimer-s-disease-risk-is-influenced-by-sex-and-docosahexaenoic-acid-status
#13
REVIEW
Matthew Pontifex, David Vauzour, Anne-Marie Minihane
An apolipoprotein E ε4 (APOE-ε4) genotype is the strongest common genetic determinant of Alzheimer's disease (AD). The pleiotropic nature of apolipoprotein E has made elucidation of the aetiological basis difficult to establish, which is further complicated by the fact that the penetrance of the APOE-ε4 allele is modulated by sex, age, and nutrition. A greater metabolic consequence of the APOE-ε4 allele is likely to contribute to the fact that two-thirds of AD patients are female. A higher tissue status of the marine n-3 fatty acid docosahexaenoic acid (DHA) is associated with a lower AD risk...
May 21, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29909176/age-related-differences-in-striatal-medial-temporal-and-frontal-involvement-during-value-based-decision-processing
#14
Yu-Shiang Su, Jheng-Ting Chen, Yong-Jheng Tang, Shu-Yun Yuan, Anna C McCarrey, Joshua Oon Soo Goh
Appropriate neural representation of value and application of decision strategies are necessary to make optimal investment choices in real life. Normative human aging alters neural selectivity and control processing in brain regions implicated in value-based decision processing including striatal, medial temporal, and frontal areas. However, the specific neural mechanisms of how these age-related functional brain changes modulate value processing in older adults remain unclear. Here, young and older adults performed a lottery-choice functional magnetic resonance imaging experiment in which probabilities of winning different magnitudes of points constituted expected values of stakes...
May 21, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29894904/functional-networks-underlying-item-and-source-memory-shared-and-distinct-network-components-and-age-related-differences
#15
Zachary A Monge, Matthew L Stanley, Benjamin R Geib, Simon W Davis, Roberto Cabeza
Although the medial temporal lobes (MTLs) are critical for both item memory (IM) and source memory (SM), the lateral prefrontal cortex and posterior parietal cortex play a greater role during SM than IM. It is unclear, however, how these differences translate into shared and distinct IM versus SM network components and how these network components vary with age. Within a sample of younger adults (YAs; n = 15, Mage  = 19.5 years) and older adults (OAs; n = 40, Mage  = 68.6 years), we investigated the functional networks underlying IM and SM...
May 21, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29909177/-18-f-fmpep-d-2-pet-imaging-shows-age-and-genotype-dependent-impairments-in-the-availability-of-cannabinoid-receptor-1-in-a-mouse-model-of-alzheimer-s-disease
#16
Jatta S Takkinen, Francisco R López-Picón, Anna K Kirjavainen, Rea Pihlaja, Anniina Snellman, Tamiko Ishizu, Eliisa Löyttyniemi, Olof Solin, Juha O Rinne, Merja Haaparanta-Solin
Contradictory findings on the role of the type 1 cannabinoid receptor (CB1 R) during the pathogenesis of Alzheimer's disease (AD) have been reported. Here, we evaluated the CB1 R brain profile in an AD mouse model using longitudinal positron emission tomography with an inverse agonist for CB1 R, [18 F]FMPEP-d2 . APP/PS1-21 and wild-type (n = 8 in each group) mice were repeatedly imaged between 6 to 15 months of age, accompanied by brain autoradiography, western blot, and CB1 R immunohistochemistry with additional mice...
May 18, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29894903/independent-effects-of-age-and-levodopa-on-reversal-learning-in-healthy-volunteers
#17
Andrew Vo, Ken N Seergobin, Penny A MacDonald
The dopamine overdose hypothesis has provided an important theoretical framework for understanding cognition in Parkinson's disease. It posits that effects of dopaminergic therapy on cognition in Parkinson's disease depend on baseline dopamine levels in brain regions that support different functions. Although functions performed by more severely dopamine-depleted brain regions improve with medication, those associated with less dopamine deficient areas are actually worsened. It is presumed that medication-related worsening of cognition owes to dopamine overdose...
May 18, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29906661/loss-of-trem2-in-microglia-leads-to-widespread-disruption-of-cell-coexpression-networks-in-mouse-brain
#18
Guillermo Carbajosa, Karim Malki, Nathan Lawless, Hong Wang, John W Ryder, Eva Wozniak, Kristie Wood, Charles A Mein, Richard J B Dobson, David A Collier, Michael J O'Neill, Angela K Hodges, Stephen J Newhouse
Rare heterozygous coding variants in the triggering receptor expressed in myeloid cells 2 (TREM2) gene, conferring increased risk of developing late-onset Alzheimer's disease, have been identified. We examined the transcriptional consequences of the loss of Trem2 in mouse brain to better understand its role in disease using differential expression and coexpression network analysis of Trem2 knockout and wild-type mice. We generated RNA-Seq data from cortex and hippocampus sampled at 4 and 8 months. Using brain cell-type markers and ontology enrichment, we found subnetworks with cell type and/or functional identity...
May 17, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29895397/targeted-next-generation-sequencing-reveals-novel-and-rare-variants-in-indian-patients-with-amyotrophic-lateral-sclerosis
#19
Priyam Narain, Ashutosh Pandey, Shruti Gupta, James Gomes, Rohit Bhatia, Perumal Vivekanandan
Studies on genetic aberrations among Indian amyotrophic lateral sclerosis (ALS) patients are limited to C9orf72 and ATXN2 repeat expansions and mutations in the SOD1 gene. In this study, we used targeted next-generation sequencing to analyze 25 ALS-associated genes in a cohort of 154 Indian ALS patients. We identified known pathogenic mutations in SOD1 (G148D; H44R), TARDBP (M337V; N267S), DAO (R199Q), and ANG (K41I). In addition, we also identified 7 potentially pathogenic missense variants that have not been previously reported in ALS patients; this includes 3 novel variants (OPTN: K489E, DAO: E121K, and SETX: L2163V) that are not reported in large population databases and 4 rare variants (CHMP2B: E45K, SQSTM1: G262R and P438L, ERBB4: R103H) with a minor allele frequency of <0...
May 17, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29861043/evaluating-the-causality-of-novel-sequence-variants-in-the-prion-protein-gene-by-example
#20
Tze How Mok, Carolin Koriath, Zane Jaunmuktane, Tracy Campbell, Susan Joiner, Jonathan D F Wadsworth, Laszlo L P Hosszu, Sebastian Brandner, Ambereen Parvez, Thomas Clement Truelsen, Eva Løbner Lund, Romi Saha, John Collinge, Simon Mead
The estimation of pathogenicity and penetrance of novel prion protein gene (PRNP) variants presents significant challenges, particularly in the absence of family history, which precludes the application of Mendelian segregation. Moreover, the ambiguities of prion disease pathophysiology renders conventional in silico predictions inconclusive. Here, we describe 2 patients with rapid cognitive decline progressing to akinetic mutism and death within 10 weeks of symptom onset, both of whom possessed the novel T201S variant in PRNP...
May 15, 2018: Neurobiology of Aging
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