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Neurobiology of Aging

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https://www.readbyqxmd.com/read/28438484/simultaneous-object-perception-deficits-are-related-to-reduced-visual-processing-speed-in-amnestic-mild-cognitive-impairment
#1
Adriana L Ruiz-Rizzo, Peter Bublak, Petra Redel, Timo Grimmer, Hermann J Müller, Christian Sorg, Kathrin Finke
Simultanagnosia, an impairment in simultaneous object perception, has been attributed to deficits in visual attention and, specifically, to processing speed. Increasing visual attention deficits manifest over the course of Alzheimer's disease (AD), where the first changes are present already in its symptomatic predementia phase: amnestic mild cognitive impairment (aMCI). In this study, we examined whether patients with aMCI due to AD show simultaneous object perception deficits and whether and how these deficits relate to visual attention...
April 4, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28438485/variations-in-the-apoe-allele-or-bdnf-val66met-polymorphism-are-not-associated-with-changes-in-cognitive-function-following-a-tertiary-education-intervention-in-older-adults-the-tasmanian-healthy-brain-project
#2
Megan E Thow, Mathew J Summers, Jeffery J Summers, Nichole L Saunders, James C Vickers
The apolipoprotein (APOE) ε4 allele and the Met variant of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism are associated with reduced cognitive function in older adults. The aim of this study was to examine the independent and interactional effect of the APOE ε4 allele and BDNF Val66Met polymorphism on cognitive function in a cohort of healthy older adults who had undertaken further university level education. Multiple group latent growth curve modeling revealed no change in cognitive function over time in APOE ε4-carriers or in BDNF Met-carriers, nor in carriers of both APOE-ε4 and BDNF-Met alleles...
April 2, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28438486/pti-125-binds-and-reverses-an-altered-conformation-of-filamin-a-to-reduce-alzheimer-s-disease-pathogenesis
#3
Hoau-Yan Wang, Kuo-Chieh Lee, Zhe Pei, Amber Khan, Kalindi Bakshi, Lindsay H Burns
We show that amyloid-β1-42 (Aβ42) triggers a conformational change in the scaffolding protein filamin A (FLNA) to induce FLNA associations with α7-nicotinic acetylcholine receptor (α7nAChR) and toll-like receptor 4 (TLR4). These aberrant associations respectively enable Aβ42's toxic signaling via α7nAChR to hyperphosphorylate tau protein, and TLR4 activation to release inflammatory cytokines. PTI-125 is a small molecule that preferentially binds altered FLNA and restores its native conformation, restoring receptor and synaptic activities and reducing its α7nAChR/TLR4 associations and downstream pathologies...
March 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28431754/effect-of-short-term-dhea-supplementation-on-serum-and-hippocampal-estrogen-concentrations-in-perimenopausal-female-rhesus-macaques
#4
Henryk F Urbanski, Krystina G Sorwell, Laszlo Prokai, Steven G Kohama
The hippocampus of rhesus macaques expresses genes that encode key enzymes involved in the intracrine conversion of dehydroepiandrosterone (DHEA) to estradiol. Therefore, it is plausible that supplementary DHEA may enhance hippocampal estradiol concentrations and help to compensate for the marked postmenopausal attenuation of circulating estrogen levels. To test this hypothesis, we used LC-MS/MS to measure estradiol and estrone concentrations in the serum and hippocampus of young and old perimenopausal female rhesus macaques, as well as old perimenopausal females that received daily DHEA (5 mg) oral supplementation for 1 week...
March 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28431287/age-and-gender-effects-of-11-c-itmm-binding-to-metabotropic-glutamate-receptor-type-1-in-healthy-human-participants
#5
Muneyuki Sakata, Jun Toyohara, Kenji Ishibashi, Kei Wagatsuma, Kenji Ishii, Ming-Rong Zhang, Kiichi Ishiwata
We examined possible age- and gender-related changes in binding of the selective antagonist N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM) to metabotropic glutamate receptor type 1 in healthy human brains. Dynamic (11)C-ITMM positron emission tomography scans (90 min) with serial arterial blood sampling were performed in 15 young and 24 older healthy adult volunteers. The total distribution volume (VT) of several brain regions was estimated with 2-tissue compartment model analysis...
March 28, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28434692/immune-hyperreactivity-of-a%C3%AE-plaque-associated-microglia-in-alzheimer-s-disease
#6
Zhuoran Yin, Divya Raj, Nasrin Saiepour, Debby Van Dam, Nieske Brouwer, Inge R Holtman, Bart J L Eggen, Thomas Möller, Joseph A Tamm, Aicha Abdourahman, Elly M Hol, Willem Kamphuis, Thomas A Bayer, Peter P De Deyn, Erik Boddeke
Alzheimer's disease (AD) is strongly associated with microglia-induced neuroinflammation. Particularly, Aβ plaque-associated microglia take on an "activated" morphology. However, the function and phenotype of these Aβ plaque-associated microglia are not well understood. We show hyperreactivity of Aβ plaque-associated microglia upon systemic inflammation in transgenic AD mouse models (i.e., 5XFAD and APP23). Gene expression profiling of Aβ plaque-associated microglia (major histocompatibility complex II(+) microglia) isolated from 5XFAD mice revealed a proinflammatory phenotype...
March 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28431286/age-related-changes-in-corticospinal-excitability-and-intracortical-inhibition-after-upper-extremity-motor-learning-a-systematic-review-and-meta-analysis
#7
Kelly M M Berghuis, John G Semmler, George M Opie, Aylin K Post, Tibor Hortobágyi
It is unclear how old age affects the neuronal mechanisms of motor learning. We reviewed the neuronal mechanisms of how healthy old and young adults acquire motor skills as assessed with transcranial magnetic stimulation. Quantitative meta-analyses of 11 studies, involving ballistic and visuomotor tasks performed by upper extremity muscles in 132 healthy old and 128 young adults, revealed that the motor practice-induced increase in corticospinal excitability (CSE) is task-dependent but not age-dependent, with an increase in CSE in both age groups after visuomotor but not ballistic training...
March 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28411410/spatio-temporal-patterns-of-event-related-potentials-related-to-audiovisual-synchrony-judgments-in-older-adults
#8
Yu Man Chan, Michael Julian Pianta, Stefan Bode, Allison Maree McKendrick
Older adults have altered perception of the relative timing between auditory and visual stimuli, even when stimuli are scaled to equate detectability. To help understand why, this study investigated the neural correlates of audiovisual synchrony judgments in older adults using electroencephalography (EEG). Fourteen younger (18-32 year old) and 16 older (61-74 year old) adults performed an audiovisual synchrony judgment task on flash-pip stimuli while EEG was recorded. All participants were assessed to have healthy vision and hearing for their age...
March 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28407521/genetic-or-pharmacological-activation-of-the-drosophila-pgc-1%C3%AE-ortholog-spargel-rescues-the-disease-phenotypes-of-genetic-models-of-parkinson-s-disease
#9
Chee-Hoe Ng, Adeline H Basil, Liting Hang, Royston Tan, Kian-Leong Goh, Sharon O'Neill, Xiaodong Zhang, Fengwei Yu, Kah-Leong Lim
Despite intensive research, the etiology of Parkinson's disease (PD) remains poorly understood and the disease remains incurable. However, compelling evidence gathered over decades of research strongly support a role for mitochondrial dysfunction in PD pathogenesis. Related to this, PGC-1α, a key regulator of mitochondrial biogenesis, has recently been proposed to be an attractive target for intervention in PD. Here, we showed that silencing of expression of the Drosophila PGC-1α ortholog spargel results in PD-related phenotypes in flies and also seem to negate the effects of AMPK activation, which we have previously demonstrated to be neuroprotective, that is, AMPK-mediated neuroprotection appears to require PGC-1α...
March 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28391068/abnormal-trajectories-in-cerebellum-and-brainstem-volumes-in-carriers-of-the-fragile-x-premutation
#10
Jun Yi Wang, David Hessl, Randi J Hagerman, Tony J Simon, Flora Tassone, Emilio Ferrer, Susan M Rivera
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder typically affecting male premutation carriers with 55-200 CGG trinucleotide repeat expansions in the FMR1 gene after age 50. The aim of this study was to examine whether cerebellar and brainstem changes emerge during development or aging in late life. We retrospectively analyzed magnetic resonance imaging scans from 322 males (age 8-81 years). Volume changes in the cerebellum and brainstem were contrasted with those in the ventricles and whole brain...
March 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28391067/n-type-ca-2-channels-are-affected-by-full-length-mutant-huntingtin-expression-in-a-mouse-model-of-huntington-s-disease
#11
Flavia R Silva, Artur S Miranda, Rebeca P M Santos, Isabella G Olmo, Gerald W Zamponi, Tomas Dobransky, Jader S Cruz, Luciene B Vieira, Fabiola M Ribeiro
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the amino-terminal region of the huntingtin (htt) protein. In addition to facilitating neurodegeneration, mutant htt is implicated in HD-related alterations of neurotransmission. Previous data showed that htt can modulate N-type voltage-gated Ca(2+) channels (Cav2.2), which are essential for presynaptic neurotransmitter release. Thus, to elucidate the mechanism underlying mutant htt-mediated alterations in neurotransmission, we investigated how Cav2...
March 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28431288/longitudinal-whole-brain-atrophy-and-ventricular-enlargement-in-nondemented-parkinson-s-disease
#12
Elijah Mak, Li Su, Guy B Williams, Michael J Firbank, Rachael A Lawson, Alison J Yarnall, Gordon W Duncan, Brit Mollenhauer, Adrian M Owen, Tien K Khoo, David J Brooks, James B Rowe, Roger A Barker, David J Burn, John T O'Brien
We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively...
March 16, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28407520/anticholinergic-drug-use-is-associated-with-episodic-memory-decline-in-older-adults-without-dementia
#13
Goran Papenberg, Lars Bäckman, Laura Fratiglioni, Erika J Laukka, Johan Fastbom, Kristina Johnell
Anticholinergic drug use is common in older adults and has been related to increased dementia risk. This suggests that users of these drugs may experience accelerated cognitive decline. So far, however, longitudinal data on this topic are absent and the available evidence is inconclusive with respect to effects on specific cognitive domains due to suboptimal control of confounding variables. We investigated whether anticholinergic medication use is associated with cognitive decline over 6 years in a population-based study of older adults (aged 60-90; n = 1473) without dementia...
March 16, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28395177/regional-amyloid-burden-and-lacune-in-pure-subcortical-vascular-cognitive-impairment
#14
Yun Jeong Hong, Chan-Mi Kim, Ji Eun Kim, Jee Hoon Roh, Jae Seung Kim, Sang Won Seo, Duk L Na, Jae-Hong Lee
We investigated the amyloid and vascular burden in Pittsburgh compound B (PiB)-negative subcortical vascular mild cognitive impairment (svMCI) and PiB-negative subcortical ischemic vascular dementia (SIVD) to elucidate the potential roles of amyloid deposition and small vessel disease (SVD). Thirty-eight svMCI patients and 42 SIVD patients were enrolled. The regional PiB uptake values and SVD markers were obtained and compared between groups. Additionally, correlations among amyloid burden, SVD, and cognition were made...
March 16, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28392172/decreased-gene-expression-of-cd2ap-in-chinese-patients-with-sporadic-alzheimer-s-disease
#15
Qing-Qing Tao, Zhi-Jun Liu, Yi-Min Sun, Hong-Lei Li, Ping Yang, De-Shan Liu, Bin Jiang, Xiao-Yan Li, Jian-Feng Xu, Zhi-Ying Wu
Many sporadic Alzheimer's disease (SAD) risk genes have been identified in the last decades, but most of them have not been consistently accepted. Here, we sought to identify SAD-associated genes and their potential mechanisms involved in SAD pathogenesis. A 2-stage design was employed. In stage 1, 95 variants in 75 genes that were previously reported as SAD-risk genes in Caucasian populations were evaluated in 1857 subjects (422 SAD patients and 1435 controls). In stage 2, a subset of promising variants found in stage 1 were further evaluated in an independent cohort of 1001 subjects (254 SAD and 747 controls)...
March 16, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28385550/currents-of-memory-recent-progress-translational-challenges-and-ethical-considerations-in-fornix-deep-brain-stimulation-trials-for-alzheimer-s-disease
#16
REVIEW
John Noel M Viaña, James C Vickers, Mark J Cook, Frederic Gilbert
The serendipitous discovery of triggered autobiographical memories and eventual memory improvement in an obese patient who received fornix deep brain stimulation in 2008 paved the way for several phase I and phase II clinical trials focused on the safety and efficacy of this potential intervention for people with Alzheimer's disease. In this article, we summarize clinical trials and case reports on fornix deep brain stimulation for Alzheimer's disease and review experiments on animal models evaluating the physiological or behavioral effects of this intervention...
March 11, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28431289/klotho-apoe%C3%AE%C2%B54-cognitive-ability-brain-size-atrophy-and-survival-a-study-in-the-aberdeen-birth-cohort-of-1936
#17
Clarisse F de Vries, Roger T Staff, Sarah E Harris, Dorota Chapko, Daniel S Williams, Polina Reichert, Trevor Ahearn, Christopher J McNeil, Lawrence J Whalley, Alison D Murray
A single copy of klotho allele KL-VS is associated with longevity, better health, increased cognition, and bigger regional brain volume. However, its longitudinal effects on cognition and brain volumes, both global and regional, in late life are unclear. In this study we show that, relative to noncarriers, KL-VS heterozygotes had (1) shorter survival; (2) smaller white matter volumes; (3) slower cognitive decline; and (4) greater right frontal lobe volumes. The KL-VS heterozygote survival and white matter volume disadvantages were unexpected...
March 7, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28419892/plasma-apolipoproteins-and-physical-and-cognitive-health-in-very-old-individuals
#18
Julia Muenchhoff, Fei Song, Anne Poljak, John D Crawford, Karen A Mather, Nicole A Kochan, Zixuan Yang, Julian N Trollor, Simone Reppermund, Kate Maston, Adam Theobald, Susanne Kirchner-Adelhardt, John B Kwok, Robyn L Richmond, Mark McEvoy, John Attia, Peter W Schofield, Henry Brodaty, Perminder S Sachdev
Apolipoproteins play a crucial role in lipid metabolism with implications in cardiovascular disease, obesity, diabetes, Alzheimer's disease, and longevity. We quantified 7 apolipoproteins in plasma in 1067 individuals aged 56-105 using immunoassays and explored relationships with APOE polymorphism ε2/3/4, vascular health, frailty, and cognition. ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH, and ApoJ decreased from mid-life, although ApoE and ApoJ had U-shaped trends. Centenarians had the highest ApoE levels and the lowest frequency of APOE ε4 allele relative to younger groups...
March 1, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28292535/maintained-memory-in-aging-is-associated-with-young-epigenetic-age
#19
Sofie Degerman, Maria Josefsson, Annelie Nordin Adolfsson, Sigrid Wennstedt, Mattias Landfors, Zahra Haider, Sara Pudas, Magnus Hultdin, Lars Nyberg, Rolf Adolfsson
Epigenetic alterations during aging have been proposed to contribute to decline in physical and cognitive functions, and accelerated epigenetic aging has been associated with disease and all-cause mortality later in life. In this study, we estimated epigenetic age dynamics in groups with different memory trajectories (maintained high performance, average decline, and accelerated decline) over a 15-year period. Epigenetic (DNA-methylation [DNAm]) age was assessed, and delta age (DNAm age - chronological age) was calculated in blood samples at baseline (age: 55-65 years) and 15 years later in 52 age- and gender-matched individuals from the Betula study in Sweden...
February 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28259365/loss-of-precuneus-dendritic-spines-immunopositive-for-spinophilin-is-related-to-cognitive-impairment-in-early-alzheimer-s-disease
#20
Zhiping Mi, Eric E Abrahamson, Angela Y Ryu, Kenneth N Fish, Robert A Sweet, Elliott J Mufson, Milos D Ikonomovic
Precuneus (PreC) cortex is affected with amyloid plaques early in Alzheimer's disease (AD), and this pathology may be associated with alterations in PreC synapses and cognitive impairment. We quantified the spinophilin-immunoreactive (ir) dendritic spine density and the intensity of spinophilin immunofluorescence, the latter as a measure of relative protein levels of spinophilin, in PreC lamina III from 33 subjects with clinical diagnoses of no cognitive impairment (NCI), mild cognitive impairment (MCI), mild-moderate AD (mAD), or severe AD (sAD)...
February 4, 2017: Neurobiology of Aging
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