Cerebrospinal fluid amyloid levels are associated with delayed memory retention in cognitively normal biomarker-negative older adults.
Abstract Alzheimer's disease is defined by abnormal levels of amyloid and tau biomarkers. Even cognitively normal older adults with clinically relevant amyloid and tau levels perform worse on memory tests. However, it is unclear if the relationship between biomarker level and memory extends below clinical thresholds. We hypothesized that even subclinical biomarker levels are associated with memory when measured with neuropsychological tests designed to detect dysfunction in preclinical disease states. In a group of cognitively normal, "biomarker-negative" older men and women, we investigated the relation...
Source: Neurobiology of Aging - August 15, 2019 Category: Geriatrics Authors: Yeung LK, Hale C, Last BS, Andrews H, Sloan RP, Honig LS, Small SA, Brickman AM Tags: Neurobiol Aging Source Type: research

Benzodiazepine use and brain amyloid load in nondemented older individuals: a florbetapir PET study in the Multidomain Alzheimer Preventive Trial cohort.
In this study, we investigated associations between chronic use of BZDs and brain amyloid load, a hallmark of AD, in 268 nondemented older individuals. F18-florbetapir positron emission tomography scans were performed to assess amyloid load as measured by standardized uptake value ratios, which were compared between chronic BZD users and nonusers using adjusted multiple linear regressions. Short- versus long-acting BZDs were also considered in the analyses. Standardized uptake value ratios were significantly lower in BZD users (n = 47) than in nonusers (n = 221), independent of multiple adjustments. The effect wa...
Source: Neurobiology of Aging - August 14, 2019 Category: Geriatrics Authors: Desmidt T, Delrieu J, Lebouvier T, Robert G, David R, Balageas AC, Surget A, Belzung C, Arlicot N, Ribeiro MJ, Payoux P, Vellas B, El-Hage W, Tavernier E, Camus V, MAPT/DSA study group Tags: Neurobiol Aging Source Type: research

Optical measures of cerebral arterial stiffness are associated with white matter signal abnormalities and cognitive performance in normal aging.
Abstract Decline in fluid abilities in normal aging is associated with increased white matter lesions, measured on T1-weighted images as white matter signal abnormalities (WMSAs). WMSAs are particularly evident in hypertensive older adults, suggesting vascular involvement. However, because hypertension is assessed systemically, the specific role of cerebral arterial stiffening in WMSAs has yet to be demonstrated. In 93 cognitively normal adults (aged 18-87 years), we used a novel method to measure cerebral arterial elasticity (pulse relaxation function [PReFx]) with diffuse optical tomography (pulse-DOT) and inves...
Source: Neurobiology of Aging - August 10, 2019 Category: Geriatrics Authors: Tan CH, Low KA, Chiarelli AM, Fletcher MA, Navarra R, Burzynska AZ, Kong TS, Zimmerman B, Maclin EL, Sutton BP, Gratton G, Fabiani M Tags: Neurobiol Aging Source Type: research

Cerebral amyloid burden is associated with white matter hyperintensity location in specific posterior white matter regions.
We examined whether cerebral amyloid and tau burden, reflected in cerebrospinal fluid amyloid-beta 1-42 (Aβ-42) and phosphorylated tau (p-tau), are related to WMH location in a cohort of 517 memory clinic patients. Two lesion mapping techniques were performed: voxel-based analyses and region of interest-based linear regression. Voxelwise associations were found between lower Aβ-42 and parieto-occipital periventricular WMHs. Regression analyses demonstrated that lower Aβ-42 correlated with larger WMH volumes in the splenium of the corpus callosum and posterior thalamic radiation, also after controlling for ma...
Source: Neurobiology of Aging - August 9, 2019 Category: Geriatrics Authors: Weaver NA, Doeven T, Barkhof F, Biesbroek JM, Groeneveld ON, Kuijf HJ, Prins ND, Scheltens P, Teunissen CE, van der Flier WM, Biessels GJ, TRACE-VCI study group Tags: Neurobiol Aging Source Type: research

A novel V272D presenilin mutation associated with logopenia, disorientation, and apraxia in an autosomal-dominant Alzheimer's disease family.
l R Abstract In the present study, a novel mutation in the presenilin 1 gene was discovered in an Iraq-native patient with early-onset Alzheimer's disease, who presented with speech impairment and memory decline at age 46 years. Magnetic resonance imaging showed a frontotemporal atrophy. Sanger sequencing identified a heterozygous T to A transversion at position 815 (c.815T>A) in the presenilin 1 gene (PSEN1), resulting in a novel missense mutation at codon 272 from valine to aspartate (V272D). We tested this PSEN1 mutation in vitro and found V272D resulted in an altered Aβ42/40 ratio. PMID:...
Source: Neurobiology of Aging - August 7, 2019 Category: Geriatrics Authors: Mengel D, Liu L, Yamamoto R, Zülow S, Deuschl C, Hermann DM, Zerr I, Selkoe DJ, Dodel R Tags: Neurobiol Aging Source Type: research

A pleiotropic role for exosomes loaded with the amyloid β precursor protein carboxyl-terminal fragments in the brain of Down syndrome patients.
A pleiotropic role for exosomes loaded with the amyloid β precursor protein carboxyl-terminal fragments in the brain of Down syndrome patients. Neurobiol Aging. 2019 Aug 01;84:26-32 Authors: Pérez-González R, Gauthier SA, Sharma A, Miller C, Pawlik M, Kaur G, Kim Y, Levy E Abstract Down syndrome (DS) is characterized by cognitive deficits throughout the life span and with the development of aging-dependent Alzheimer's type neuropathology, which is related to the triplication of the amyloid β precursor protein (APP) gene. A dysfunctional endosomal system in neurons is an early c...
Source: Neurobiology of Aging - August 1, 2019 Category: Geriatrics Authors: Pérez-González R, Gauthier SA, Sharma A, Miller C, Pawlik M, Kaur G, Kim Y, Levy E Tags: Neurobiol Aging Source Type: research

Staging the cognitive continuum in prodromal Alzheimer's disease with episodic memory.
We examined 387 MCI amyloid-positive subjects, cognitively staged as "early" or "late" on the basis of episodic memory impairment. Cross-sectional and longitudinal comparisons between these 2 groups were performed for each amyloid, tau, and neurodegeneration (AT(N)) profile. Cross-sectional analyses indicate that "early" MCI represents a transitional phase between normal cognition and "late" MCI in the AD biomarker pathway. After adjusting by confounders and levels of A, T, and (N), "late" MCI progressed significantly faster than "early" MCI only in profiles with ...
Source: Neurobiology of Aging - July 30, 2019 Category: Geriatrics Authors: Moscoso A, Silva-Rodríguez J, Aldrey JM, Cortés J, Fernández-Ferreiro A, Gómez-Lado N, Ruibal Á, Aguiar P, Alzheimer's Disease Neuroimaging Initiative Tags: Neurobiol Aging Source Type: research

Microstructural changes in the brain mediate the association of AK4, IGFBP5, HSPB2, and ITPK1 with cognitive decline.
This study included 521 participants (mean age 90.3, 65.9-108.3) with the postmortem reciprocal of transverse relaxation time (R2) magnetic resonance image. All participants came from one of the 2 ongoing longitudinal cohorts of aging and dementia, the Religious Orders Study and Rush Memory and Aging Project. Higher abundance of AK4, HSPB2, and IGFBP5 was associated with faster cognitive decline and mediated through lower postmortem R2 in the frontal and temporal white matter regions. In contrast, higher abundance of ITPK1 was associated with slower cognitive decline and mediated through higher postmortem R2 in the frontal...
Source: Neurobiology of Aging - July 26, 2019 Category: Geriatrics Authors: Kim N, Yu L, Dawe R, Petyuk VA, Gaiteri C, De Jager PL, Schneider JA, Arfanakis K, Bennett DA Tags: Neurobiol Aging Source Type: research

Subjective cognitive decline, brain imaging biomarkers, and cognitive functioning in patients with a history of vascular disease: the SMART-Medea study.
Abstract We estimated associations of subjective cognitive decline (SCD) with neuroimaging markers of dementia and cognitive functioning in patients with a history of vascular disease without objective cognitive impairment. Within the Second Manifestations of ARTerial disease-Memory, depression and aging study, 599 patients (62 ± 9 years) had 1.5 T brain magnetic resonance imaging and cognitive testing at the baseline and after 8 years of follow-up. Using multiple regression analyses, we estimated cross-sectional and longitudinal associations of SCD according to research criteria with volumes...
Source: Neurobiology of Aging - July 24, 2019 Category: Geriatrics Authors: Blom K, Koek HL, Zwartbol MHT, van der Graaf Y, Kesseler L, Biessels GJ, Geerlings MI, SMART Study Group Tags: Neurobiol Aging Source Type: research

Reduced cognitive performance in aged rats correlates with increased excitation/inhibition ratio in the dentate gyrus in response to lateral entorhinal input.
Abstract Aging often impairs cognitive functions associated with the medial temporal lobe (MTL). Anatomical studies identified the layer II pyramidal cells of the lateral entorhinal cortex (LEC) as one of the most vulnerable elements within the MTL. These cells provide a major excitatory input to the dentate gyrus hippocampal subfield through synapses onto granule cells and onto local inhibitory interneurons, and a fraction of these contacts are lost in aged individuals with impaired learning. Using optogenetics, we evaluated the functional status of the remaining inputs in an outbred rat model of aging that disti...
Source: Neurobiology of Aging - July 23, 2019 Category: Geriatrics Authors: Tran T, Bridi M, Koh MT, Gallagher M, Kirkwood A Tags: Neurobiol Aging Source Type: research

Age-related changes in cortical connectivity influence the neuromodulatory effects of transcranial electrical stimulation.
Abstract Transcranial electrical stimulation (tES) is a potentially viable tool for boosting cognitive performance in aging. However, most knowledge on tES effects is based on studies involving young adults. Here, we applied tES (transcranial random noise stimulation [tRNS] as an effective stimulation and anodal transcranial direct current stimulation [atDCS] as a "control" stimulation) to the visual cortex during visual perceptual learning (VPL) in healthy young and older individuals. Moreover, we measured transcranial magnetic stimulation-evoked potentials to investigate the neurophysiological underpin...
Source: Neurobiology of Aging - July 23, 2019 Category: Geriatrics Authors: Fertonani A, Pirulli C, Bollini A, Miniussi C, Bortoletto M Tags: Neurobiol Aging Source Type: research

Associations among amyloid status, age, and longitudinal regional brain atrophy in cognitively unimpaired older adults.
Abstract The goal of this study was to compare regional brain atrophy patterns in cognitively unimpaired (CU) older adults with and without brain accumulation of amyloid-β (Aβ) to elucidate contributions of Aβ, age, and other variables to atrophy rates. In 80 CU participants from the Alzheimer's Disease Neuroimaging Initiative, we determined effects of Aβ and age on longitudinal, regional atrophy rates, while accounting for confounding variables including sex, APOE ε4 genotype, white matter lesions, and cerebrospinal fluid total and phosphorylated tau levels. We not only found overlappi...
Source: Neurobiology of Aging - July 22, 2019 Category: Geriatrics Authors: Rl N, Ps I, N M, D T, S B, D T, N S, Ps A, Mw W, Alzheimer's Disease Neuroimaging Initiative Tags: Neurobiol Aging Source Type: research

Longitudinal brain atrophy patterns and neuropsychological performance in older adults with HIV-associated neurocognitive disorder compared with early Alzheimer's disease.
Abstract Older HIV-infected patients are at risk for both HIV-associated neurocognitive disorder (HAND) and Alzheimer's disease. We investigated neuroimaging and neuropsychological performance of 61 virally suppressed older adults with HAND (mean (SD) age 64.3 (3.9) years), 53 demographically matched individuals with mild cognitive impairment of the Alzheimer's type (MCI-AD; 65.0 [4.8]), and 89 healthy controls (65.0 [4.3]) cross-sectionally and over 20 months. At the baseline, both disease groups exhibited lower volumes in multiple cortical and subcortical regions compared with controls. Hippocampal volume d...
Source: Neurobiology of Aging - July 11, 2019 Category: Geriatrics Authors: Milanini B, Samboju V, Cobigo Y, Paul R, Javandel S, Hellmuth J, Allen I, Miller B, Valcour V Tags: Neurobiol Aging Source Type: research

Tyrosol, a simple phenol from EVOO, targets multiple pathogenic mechanisms of neurodegeneration in a C.  elegans model of Parkinson's disease.
Tyrosol, a simple phenol from EVOO, targets multiple pathogenic mechanisms of neurodegeneration in a C. elegans model of Parkinson's disease. Neurobiol Aging. 2019 Jul 11;82:60-68 Authors: García-Moreno JC, Porta de la Riva M, Martínez-Lara E, Siles E, Cañuelo A Abstract Parkinson's disease (PD) is a common neurodegenerative disorder involving α-synuclein (α-syn) aggregation, oxidative stress, dysregulation of redox metal homeostasis, and neurotoxicity. Different phenolic compounds with known antioxidant or antichelating properties have been shown to also interfer...
Source: Neurobiology of Aging - July 11, 2019 Category: Geriatrics Authors: García-Moreno JC, Porta de la Riva M, Martínez-Lara E, Siles E, Cañuelo A Tags: Neurobiol Aging Source Type: research

Transforming growth factor beta 1 signaling is altered in the spinal cord and muscle of amyotrophic lateral sclerosis mice and patients.
ati M Abstract Gender differences characterize amyotrophic lateral sclerosis (ALS). Because ALS patients have increased circulating levels of transforming growth factor beta 1 (TGFB1), here we analyzed gender and disease progression-related modification of TGFB1 and its related signaling molecules in the spinal cord and skeletal muscle of ALS mice and in muscle biopsies from sporadic ALS patients. At presymptomatic stage, Tgfb1 mRNA expression is reduced in the mouse spinal cord but is increased selectively in the male skeletal muscle. At symptomatic stage, it is induced both in the mouse spinal cord and muscle, a...
Source: Neurobiology of Aging - July 10, 2019 Category: Geriatrics Authors: Meroni M, Crippa V, Cristofani R, Rusmini P, Cicardi ME, Messi E, Piccolella M, Tedesco B, Ferrari V, Sorarù G, Pennuto M, Poletti A, Galbiati M Tags: Neurobiol Aging Source Type: research

Late-life brain perfusion after prenatal famine exposure.
Abstract Early nutritional deprivation may cause irreversible damage to the brain and seems to affect cognitive function in older age. We investigated whether prenatal undernutrition was associated with brain perfusion differences in older age. We acquired Arterial spin labeling scans in 118 Dutch famine birth cohort members. Using linear regression analyses, cerebral blood flow was compared between exposed and unexposed groups in gray matter (GM) and white matter (WM), perfusion territories, the neurodegeneration-related regions anterior and posterior cingulate cortex and precuneus. Furthermore, we compared the G...
Source: Neurobiology of Aging - July 8, 2019 Category: Geriatrics Authors: de Rooij SR, Mutsaerts HJMM, Petr J, Asllani I, Caan MWA, Groot P, Nederveen AJ, Schwab M, Roseboom TJ Tags: Neurobiol Aging Source Type: research

Genetic risk for Alzheimer's disease and functional brain connectivity in children and adolescents.
I, Salum GA Abstract Research suggested accumulation of tau proteins might lead to the degeneration of functional networks. Studies investigating the impact of genetic risk for Alzheimer's disease (AD) on early brain connections might shed light on mechanisms leading to AD development later in life. Here, we aim to investigate whether the polygenic risk score for Alzheimer's disease (AD-PRS) influences the connectivity among regions susceptible to tau pathology during childhood and adolescence. Participants were youth, aged 6-14 years, and recruited in Porto Alegre (discovery sample, n = 332) and S&atild...
Source: Neurobiology of Aging - July 6, 2019 Category: Geriatrics Authors: Axelrud LK, Sato JR, Santoro ML, Talarico F, Pine DS, Rohde LA, Zugman A, Junior EA, Bressan RA, Grassi-Oliveira R, Pan PM, Hoffmann MS, Simioni AR, Guinjoan SM, Hakonarson H, Brietzke E, Gadelha A, Pellegrino da Silva R, Hoexter MQ, Miguel EC, Belangero Tags: Neurobiol Aging Source Type: research

Association of PPP2R1A with Alzheimer's disease and specific cognitive domains.
group Abstract In an attempt to identify novel genetic variants associated with sporadic Alzheimer's disease (AD), a genome-wide association study was performed on a population isolate from Eastern Canada, referred to as the Québec Founder Population (QFP). In the QFP cohort, the rs10406151 C variant on chromosome 19 is associated with higher AD risk and younger age at AD onset in APOE4- individuals. After surveying the region surrounding this intergenic polymorphism for brain cis-eQTL associations in BRAINEAC, we identified PPP2R1A as the most likely target gene modulated by the rs10406151 C vari...
Source: Neurobiology of Aging - July 2, 2019 Category: Geriatrics Authors: Miron J, Picard C, Labonté A, Auld D, Breitner J, Poirier J, United Kingdom Brain Expression Consortium, PREVENT-AD research group Tags: Neurobiol Aging Source Type: research

Reduced sensory-evoked structural plasticity in the aging barrel cortex.
Abstract Impairments in synaptic connectivity have been linked to cognitive deficits in age-related neurodegenerative disorders and healthy aging. However, the anatomical and structural bases of these impairments have not been identified yet. A hallmark of neural plasticity in young adults is short-term synaptic rearrangement, yet aged animals already display higher synaptic turnover rates at the baseline. Using two-photon excitation (2PE) microscopy, we explored if this elevated turnover alters the aged brain's response to plasticity. Following a sensory-evoked plasticity protocol involving whisker stimulation, a...
Source: Neurobiology of Aging - June 26, 2019 Category: Geriatrics Authors: Voglewede RL, Vandemark KM, Davidson AM, DeWitt AR, Heffler MD, Trimmer EH, Mostany R Tags: Neurobiol Aging Source Type: research

Pharmacological antagonism of histamine H2R ameliorated L-DOPA-induced dyskinesia via normalization of GRK3 and by suppressing FosB and ERK in PD.
Abstract Parkinson's disease (PD) is often managed with L-3,4-dihydroxyphenylalanine (L-DOPA), which is still the gold standard to relieve the clinical motor symptoms of PD. However, chronic use of L-DOPA leads to significant motor complications, especially L-DOPA-induced dyskinesia (LID), which limit the therapeutic benefit. Few options are available for the pharmacological management of LID partly due to the inadequacy of our mechanistic understanding of the syndrome. We focused on the role of the histamine (HA) H2 receptor (H2R) in the striatum, which others have shown to be involved in the development of LID. ...
Source: Neurobiology of Aging - June 19, 2019 Category: Geriatrics Authors: Ahmed MR, Jayakumar M, Ahmed MS, Zamaleeva AI, Tao J, Li EH, Job JK, Pittenger C, Ohtsu H, Rajadas J Tags: Neurobiol Aging Source Type: research

A 4R tauopathy develops without amyloid deposits in aged cat brains.
Abstract Human tauopathies are neurodegenerative diseases with accumulation of abnormally phosphorylated and aggregated tau proteins forming neurofibrillary tangles. We investigated the development of tau pathology in aged cat brains as a model of neurofibrillary tangle formation occurring spontaneously during aging. In 4 of 6 cats aged between 18 and 21 years, we found a somatodendritic accumulation of phosphorylated and aggregated tau in neurons and oligodendrocytes. Two of these 4 cats had no amyloid immunoreactivity. These tau inclusions were mainly composed of 4R tau isoforms and straight filaments and c...
Source: Neurobiology of Aging - June 14, 2019 Category: Geriatrics Authors: Poncelet L, Ando K, Vergara C, Mansour S, Suain V, Yilmaz Z, Reygel A, Gilissen E, Brion JP, Leroy K Tags: Neurobiol Aging Source Type: research

A patient with early-onset Alzheimer's disease with a novel PSEN1 p.Leu424Pro mutation.
Abstract "Presenilin 1" (PSEN1) gene mutations are the major known genetic cause of early-onset Alzheimer's disease. Herein, we report a novel heterozygous PSEN1 mutation (p.Leu424Pro) in a Turkish patient presenting with deterioration of short-term memory and visuospatial skills starting at the age of 47 years. This novel mutation is located in the conserved residue of transmembrane domain 8 coded by exon 12. At the protein level, this mutation caused a disruption in the alpha helix structure of PSEN1. The structural and possible functional consequences of the mutation suggest that it has probably ...
Source: Neurobiology of Aging - June 13, 2019 Category: Geriatrics Authors: Guven G, Erginel-Unaltuna N, Samanci B, Gulec C, Hanagasi H, Bilgic B Tags: Neurobiol Aging Source Type: research

Temporal progression of Alzheimer's disease in brains and intestines of transgenic mice.
Abstract The amyloid beta (Aβ) peptide is associated with the neurodegenerative and inflammatory changes in brains affected by Alzheimer's disease (AD). We hypothesized that the enteric nervous system also produces Aβ in an intestinal component of disease. To test this idea, we compared C57BL/6 wild-type (WT) male and female mice to two models of Alzheimer's disease, amyloid precursor protein (APP)/presenilin 1 (PS1) mice and amyloid precursor protein NL-G-F (AppNL-G-F) mice, at 3, 6, and 12 months of age. Brain Aβ plaque deposition in AppNL-G-F mice preceded that in the APP/PS1 mice, observabl...
Source: Neurobiology of Aging - June 13, 2019 Category: Geriatrics Authors: Manocha GD, Floden AM, Miller NM, Smith AJ, Nagamoto-Combs K, Saito T, Saido TC, Combs CK Tags: Neurobiol Aging Source Type: research

The missense p.Trp7Arg mutation in GRN gene leads to progranulin haploinsufficiency.
Ber I Abstract GRN null mutations are among the main genetic causes of frontotemporal dementia through progranulin haploinsufficiency. Most missense mutations are considered not pathogenic. The p.Trp7Arg substitution is localized within the signal peptide domain and no formal evidence for its pathogenicity has yet been provided. We identified the p.Trp7Arg substitution in 3 carriers with low plasma progranulin levels. This evidences that this missense mutation leads to functional haploinsufficiency and should thus be considered pathogenic. Assessing the pathogenicity of variants of unknown significance has signifi...
Source: Neurobiology of Aging - June 10, 2019 Category: Geriatrics Authors: Saracino D, Sellami L, Clot F, Camuzat A, Lamari F, Rucheton B, Benyounes I, Roué-Jagot C, Lagarde J, Sarazin M, Jornea L, Forlani S, LeGuern E, Dubois B, Brice A, Le Ber I Tags: Neurobiol Aging Source Type: research

Identification of a novel PSEN1 Gly111Val missense mutation in a Chinese pedigree with early-onset Alzheimer's disease.
Abstract Presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) genes account for the majority of autosomal dominant Alzheimer's disease (AD), with PSEN1 being the most common. We screened these genes for mutations in a Chinese proband from an autosomal dominant early-onset AD pedigree. Early-onset AD is defined as the age at onset of AD  T) of PSEN1, which results in a missense mutation (p.Gly111Val), was identified. Three prediction programs suggested this mutation was disease causing. When PSEN1 Gly111Val was overexpressed in HEK293/APPswe cells, the ratio of Aβ42/Aβ40 wa...
Source: Neurobiology of Aging - May 31, 2019 Category: Geriatrics Authors: Qiu Q, Jia L, Wang Q, Zhao L, Jin H, Li T, Quan M, Xu L, Li B, Li Y, Jia J Tags: Neurobiol Aging Source Type: research

Mice heterozygous for the Cdh23/Ahl1 mutation show age-related deficits in auditory temporal processing.
In this study, we used the amplitude modulation following response (AMFR) to test whether mice heterozygous for Cdh23735A> G have an auditory phenotype that includes temporal processing deficits. The hearing of mice heterozygous for the Cdh23735A> G mutation was compared with age-matched mice homozygous for either the mutation or the wild type in 3 cohorts of mice of both sexes at 2-3, 6, and 12 months of age. The AMFR technique was used to generate objective hearing thresholds for all mice across their range of hearing and to test their temporal processing. We found a genotype-dependent hearing loss in mice hom...
Source: Neurobiology of Aging - May 30, 2019 Category: Geriatrics Authors: Burghard AL, Morel NP, Oliver DL Tags: Neurobiol Aging Source Type: research

Visuomotor task acquisition is reduced by priming paired associative stimulation in older adults.
Abstract Transcranial magnetic stimulation may represent an effective means for improving motor function in the elderly. The aim of this study was therefore to investigate the effects of paired associative stimulation (PAS; a plasticity-inducing transcranial magnetic stimulation paradigm) on acquisition of a novel visuomotor task in young and older adults. Fourteen young (20.4 ± 0.6 years) and 13 older (69.0 ± 1.6 years) adults participated in 3 experimental sessions during which training was preceded (primed) by PAS. Within each session, the interstimulus interval used for PAS was set at e...
Source: Neurobiology of Aging - May 29, 2019 Category: Geriatrics Authors: Opie GM, Hand BJ, Coxon JP, Ridding MC, Ziemann U, Semmler JG Tags: Neurobiol Aging Source Type: research

The value of hippocampal volume, shape, and texture for 11-year prediction of dementia: a population-based study.
jne M Abstract Hippocampal volume and shape are known magnetic resonance imaging biomarkers of neurodegeneration. Recently, hippocampal texture has been shown to improve prediction of dementia in patients with mild cognitive impairment, but it is unknown whether texture adds prognostic information beyond volume and shape and whether the predictive value extends to cognitively healthy individuals. Using 510 subjects from the Rotterdam Study, a prospective, population-based cohort study, we investigated if hippocampal volume, shape, texture, and their combination were predictive of dementia and determined how predic...
Source: Neurobiology of Aging - May 28, 2019 Category: Geriatrics Authors: Achterberg HC, Sørensen L, Wolters FJ, Niessen WJ, Vernooij MW, Ikram MA, Nielsen M, de Bruijne M Tags: Neurobiol Aging Source Type: research

One-carbon metabolism gene polymorphisms are associated with cognitive trajectory among African-American adults.
Abstract The sex-specific link between longitudinal annual rate of cognitive change (LARCC) and polymorphisms in one-carbon metabolism enzymatic genes remains unclear, particularly among African-American adults. We tested associations of 14 single nucleotide polymorphisms (SNPs) from MTHFR, MTRR, MTR, and SHMT genes and select MTHFR haplotypes and latent classes (SNPHAP/SNPLC) with LARCC. Up to 797 African-American participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (age: 30-64 y, 52% women) had 1.6-1.7 (i.e., 1 or 2) repeated measures (follow-up time, mean = 4.69 y...
Source: Neurobiology of Aging - May 23, 2019 Category: Geriatrics Authors: Beydoun MA, Tajuddin SM, Shaked D, Beydoun HA, Evans MK, Zonderman AB Tags: Neurobiol Aging Source Type: research

The relationship between domain-specific subjective cognitive decline and Alzheimer's pathology in normal elderly adults.
Abstract We evaluated the associations of subjective (self-reported everyday cognition [ECog]) and objective cognitive measures with regional amyloid-β (Aβ) and tau accumulation in 86 clinically normal elderly subjects from the Alzheimer's Disease Neuroimaging Initiative. Regression analyses were conducted to identify whether individual ECog domains (Memory, Language, Organization, Planning, Visuospatial, and Divided Attention) were equally or differentially associated with regional [18F]florbetapir and [18F]flortaucipir uptake and how these associations compared to those obtained with objective cognitiv...
Source: Neurobiology of Aging - May 23, 2019 Category: Geriatrics Authors: Shokouhi S, Conley AC, Baker SL, Albert K, Kang H, Gwirtsman HE, Newhouse PA, Alzheimer's Disease Neuroimaging Initiative Tags: Neurobiol Aging Source Type: research

Lifespan normative data on rates of brain volume changes.
va D, Vaneckova M, Gasperini C, Ruggeri S, De Stefano N, MAGNIMS Study Group Abstract We provide here normative values of yearly percentage brain volume change (PBVC/y) as obtained with Structural Imaging Evaluation, using Normalization, of Atrophy, a widely used open-source software, developing a PBVC/y calculator for assessing the deviation from the expected PBVC/y in patients with neurological disorders. We assessed multicenter (34 centers, 11 acquisition protocols) magnetic resonance imaging data of 720 healthy participants covering the whole adult lifespan (16-90 years). Data of 421 participants with a f...
Source: Neurobiology of Aging - May 22, 2019 Category: Geriatrics Authors: Battaglini M, Gentile G, Luchetti L, Giorgio A, Vrenken H, Barkhof F, Cover KS, Bakshi R, Chu R, Sormani MP, Enzinger C, Ropele S, Ciccarelli O, Wheeler-Kingshott C, Yiannakas M, Filippi M, Rocca MA, Preziosa P, Gallo A, Bisecco A, Palace J, Kong Y, Horak Tags: Neurobiol Aging Source Type: research

Genome-wide association study identifies Alzheimer's risk variant in MS4A6A influencing cerebrospinal fluid sTREM2 levels.
Abstract The triggering receptor expressed on myeloid cells 2 (TREM2) gene has been reported to increase the risk of Alzheimer's disease (AD). The soluble TREM2 protein (sTREM2) in cerebrospinal fluid (CSF) was also associated with AD. However, the role of sTREM2 in AD and its genetic modifiers remain unclear. We carried out a genome-wide association study for CSF sTREM2 levels using participants from the Alzheimer's Disease Neuroimaging Initiative and validated the significant association in an independent cohort from Chinese Alzheimer's Biomarker and LifestylE study. rs7232 in membrane spanning 4-domains A6A (MS...
Source: Neurobiology of Aging - May 21, 2019 Category: Geriatrics Authors: Hou XH, Bi YL, Tan MS, Xu W, Li JQ, Shen XN, Dou KX, Tan CC, Tan L, Alzheimer's Disease Neuroimaging Initiative, Yu JT Tags: Neurobiol Aging Source Type: research

Novel presenilin 1 mutation (p.Thr-Pro116-117Ser-Thr) in a Spanish family with early-onset Alzheimer's disease.
We describe the clinical and genetic study of a 37-year-old male patient with a novel mutation in PSEN1 (p.Thr-Pro116-117Ser-Thr). We have studied the pedigree of his family with a further 9 members affected, all of them with onset in their 30s. We have also described the clinical data and results of brain biopsies in 2 of them. DNA sequencing of a tissue sample from an uncle of the patient, who died of AD in the 80s, showed the same mutation as in the patient. These data and predictive analysis indicate the pathogenicity of the mutation. PMID: 31204041 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 20, 2019 Category: Geriatrics Authors: Blanco JA, Alonso A, Blanco J, Rojo E, Tellería JJ, Torres MA, Uribe F Tags: Neurobiol Aging Source Type: research

Regional patterns of 18F-florbetaben uptake in presenilin 1 mutation carriers.
ña F, Sánchez-Valle R Abstract Individuals with autosomal dominant Alzheimer's disease (ADAD) present amyloid deposits before symptoms onset. We aimed to investigate efficacy and safety of 18F-florbetaben (FBB) for assessing amyloid deposition in ADAD. We acquired FBB positron emission tomography and magnetic resonance imaging of 25 individuals from PSEN1 families (NCT02362880). We studied individual uptake patterns, group differences, and correlation with estimated years to symptoms onset, as well as adverse events. We found that asymptomatic carriers (N = 14) showed increased FBB uptake across...
Source: Neurobiology of Aging - May 17, 2019 Category: Geriatrics Authors: Sala-Llonch R, Falgàs N, Bosch B, Fernández-Villullas G, Balasa M, Antonell A, Perissinotti A, Pavía J, Campos F, Lladó A, Lomeña F, Sánchez-Valle R Tags: Neurobiol Aging Source Type: research

Cyclic O3 exposure synergizes with aging leading to memory impairment in male APOE ε3, but not APOE ε4, targeted replacement mice.
In this study, we tested the hypothesis that O3 exposure synergizes with the genetic risk factor APOE ε4 and aging leading to AD, using male apolipoprotein E (apoE)4 and apoE3 targeted replacement mice as men have increased risk exposure to high levels of O3 via working environments and few studies have addressed APOE ε4 effects on males. Surprisingly, our results show that O3 exposure impairs memory in old apoE3, but not old apoE4 or young apoE3 and apoE4, male mice. Further studies show that old apoE4 mice have increased hippocampal activities or expression of some enzymes involved in antioxidant defense,...
Source: Neurobiology of Aging - May 17, 2019 Category: Geriatrics Authors: Jiang C, Stewart LT, Kuo HC, McGilberry W, Wall SB, Liang B, van Groen T, Bailey SM, Kim YI, Tipple TE, Jones DP, McMahon LL, Liu RM Tags: Neurobiol Aging Source Type: research

Synergism between fornix microstructure and beta amyloid accelerates memory decline in clinically normal older adults.
In conclusion, altered fornix microstructure may accelerate memory decline in preclinical Alzheimer's disease. PMID: 31207468 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 16, 2019 Category: Geriatrics Authors: Rabin JS, Perea RD, Buckley RF, Johnson KA, Sperling RA, Hedden T Tags: Neurobiol Aging Source Type: research

Age- and disease-related cerebral white matter changes in patients with Parkinson's disease.
Abstract As age and Parkinson's disease (PD) both play a role in the degeneration of brain white matter, we aimed to investigate a possible interaction effect of age and disease presence on white matter integrity in patients with PD. We studied white matter hyperintensity volume, global fractional anisotropy, mean diffusivity and mean magnetization transfer ratio of normal appearing white matter in 163 patients with PD and 218 age- and gender-matched healthy control subjects. We investigated the relationship between age and these parameters in both groups, and interaction between age and disease presence. Patients...
Source: Neurobiology of Aging - May 13, 2019 Category: Geriatrics Authors: de Schipper LJ, Hafkemeijer A, Bouts MJRJ, van der Grond J, Marinus J, Henselmans JML, van Hilten JJ Tags: Neurobiol Aging Source Type: research

An analog derived from phenylpropanoids ameliorates Alzheimer's disease-like pathology and protects mitochondrial function.
Abstract The abnormal proliferation and neurogenesis of neural progenitor cells (NPCs) is usually associated with the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). Mitochondrial stress is one of the most prominent features of AD and is thought to be involved in the impairment of the neurogenesis and proliferation of NPCs. Thus, restoring mitochondrial function by pharmaceutical intervention may alleviate disease-related defects in neurogenesis and is considered a potential therapeutic strategy for AD. In the present study, we found that the oral administration of PL201A, a design...
Source: Neurobiology of Aging - May 9, 2019 Category: Geriatrics Authors: Huang S, Cao X, Zhou Y, Shi F, Xin S, He S, An Y, Gao L, Yang Y, Yu B, Pei G Tags: Neurobiol Aging Source Type: research

A novel mutation in PSEN1 (p.T119I) in an Argentine family with early- and late-onset Alzheimer's disease.
, Surace EI Abstract Mutations in PSEN1 are the most common cause of early-onset Alzheimer's disease (AD). In this article, we present an Argentine family with autosomal dominant early- and late-onset AD. The proband and 6 family members were available for genetic testing and clinical and neuropsychological assessments. Cerebrospinal fluid biomarkers were analyzed in the proband and a cousin (mutation carrier), who also underwent positron emission tomography using F-18-2-fluoro-2-deoxy-D-glucose and Pittsburgh compound B. Exon sequencing of PSEN1, PSEN2, and APP revealed a novel heterozygous variant in PSEN1 (c.35...
Source: Neurobiology of Aging - May 9, 2019 Category: Geriatrics Authors: Itzcovich T, Chrem-Méndez P, Vázquez S, Barbieri-Kennedy M, Niikado M, Martinetto H, Allegri R, Sevlever G, Surace EI Tags: Neurobiol Aging Source Type: research

The role of C9orf72 in neurodegenerative disorders: a systematic review, an updated meta-analysis, and the creation of an online database.
Abstract A pathologic expansion of a noncoding GGGGCC hexanucleotide repeat of the C9orf72 gene has been strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) cases predominantly in Caucasian populations. In the last decade, scientific interest had been drawn to this gene and many studies conducted have shown a possible correlation with other neurodegenerative diseases as well. We performed an extensive literature search for C9orf72 mutation and its frequency in various neurological and psychiatric diseases. In addition, we performed a meta-analysis of the data...
Source: Neurobiology of Aging - April 24, 2019 Category: Geriatrics Authors: Marogianni C, Rikos D, Provatas A, Dadouli K, Ntellas P, Tsitsi P, Patrinos G, Dardiotis E, Hadjigeorgiou G, Xiromerisiou G Tags: Neurobiol Aging Source Type: research

APOE effects on cognition from childhood to adolescence.
Abstract The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = -0.13), with larger eff...
Source: Neurobiology of Aging - April 18, 2019 Category: Geriatrics Authors: Reynolds CA, Smolen A, Corley RP, Munoz E, Friedman NP, Rhee SH, Stallings MC, DeFries JC, Wadsworth SJ Tags: Neurobiol Aging Source Type: research

Individual slow-wave morphology is a marker of aging.
izs R Abstract Slow-wave activity is a hallmark of deep non-rapid eye movement sleep. Scalp slow wave morphology is stereotypical and it is highly correlated with the synchronized onset and cessation of cortical neuronal firing measured from the surface or depth of the cortex. It is also strongly affected by aging, and these changes are causally associated with age-related cognitive decline. We investigated how normal aging affects the individual morphology of the slow wave and whether these changes are captured by the summary slow wave parameters generally used in the literature. We recorded full-night polysomnog...
Source: Neurobiology of Aging - April 16, 2019 Category: Geriatrics Authors: Ujma PP, Simor P, Steiger A, Dresler M, Bódizs R Tags: Neurobiol Aging Source Type: research

Predicting Alzheimer's disease severity by means of TMS-EEG coregistration.
Abstract Clinical manifestations of Alzheimer's disease (AD) are associated with a breakdown in large-scale communication, such that AD may be considered as a "disconnection syndrome." An established method to test effective connectivity is the combination of transcranial magnetic stimulation with electroencephalography (TMS-EEG) because the TMS-induced cortical response propagates to distant anatomically connected regions. To investigate whether prefrontal connectivity alterations may predict disease severity, we explored the relationship of dorsolateral prefrontal cortex connectivity (derived from TMS-...
Source: Neurobiology of Aging - April 13, 2019 Category: Geriatrics Authors: Bagattini C, Mutanen TP, Fracassi C, Manenti R, Cotelli M, Ilmoniemi RJ, Miniussi C, Bortoletto M Tags: Neurobiol Aging Source Type: research

Reduced serotonin receptors and transporters in normal aging adults: a meta-analysis of PET and SPECT imaging studies.
Abstract Alterations in serotonin (5-HT) function have been hypothesized to underlie a range of physiological, emotional, and cognitive changes in older age. Here, we conducted a quantitative synthesis and comparison of the effects of age on 5-HT receptors and transporters from cross-sectional positron emission tomography and single-photon emission computed tomography imaging studies. Random-effects meta-analyses of 31 studies including 1087 healthy adults yielded large negative effects of age in 5-HT-2A receptors (largest in global cortex), moderate negative effects of age in 5-HT transporters (largest in thalamu...
Source: Neurobiology of Aging - April 5, 2019 Category: Geriatrics Authors: Karrer TM, McLaughlin CL, Guaglianone CP, Samanez-Larkin GR Tags: Neurobiol Aging Source Type: research

Correlation between plasma and CSF concentrations of kynurenine pathway metabolites in Alzheimer's disease and relationship to amyloid- β and tau.
Correlation between plasma and CSF concentrations of kynurenine pathway metabolites in Alzheimer's disease and relationship to amyloid-β and tau. Neurobiol Aging. 2019 Apr 01;80:11-20 Authors: Jacobs KR, Lim CK, Blennow K, Zetterberg H, Chatterjee P, Martins RN, Brew BJ, Guillemin GJ, Lovejoy DB Abstract Chronic kynurenine pathway (KP) activation is implicated in Alzheimer's disease (AD) pathophysiology and results in quinolinic acid-induced excitotoxic stimulation of the N-methyl-D-aspartate receptor. However, most studies focus on plasma and it is unclear if peripheral concentrations reflect br...
Source: Neurobiology of Aging - April 1, 2019 Category: Geriatrics Authors: Jacobs KR, Lim CK, Blennow K, Zetterberg H, Chatterjee P, Martins RN, Brew BJ, Guillemin GJ, Lovejoy DB Tags: Neurobiol Aging Source Type: research

Relevance of the interplay between amyloid and tau for cognitive impairment in early Alzheimer's disease.
JR Abstract Amyloid β (Aβ) and tau are key hallmark features of Alzheimer's disease (AD) neuropathology. The interplay of Aβ and tau for cognitive impairment in early AD was examined with cross-sectional analysis, measured by cerebrospinal fluid biomarkers (Aβ1-42, total tau [t-tau], and phosphorylated tau [p-tau181P]), and on cognitive performance by the repeatable battery for assessment of neuropsychological status (RBANS). Participants (n = 246) included cognitively normal (Aβ-), mild cognitively impaired (Aβ-), preclinical AD (Aβ+), and prodromal AD (Aβ+). Overall, cogn...
Source: Neurobiology of Aging - April 1, 2019 Category: Geriatrics Authors: Timmers M, Tesseur I, Bogert J, Zetterberg H, Blennow K, Börjesson-Hanson A, Baquero M, Boada M, Randolph C, Tritsmans L, Van Nueten L, Engelborghs S, Streffer JR Tags: Neurobiol Aging Source Type: research

Cue-related processing accounts for age differences in phasic alerting.
In this study, we investigated the neural underpinnings of age differences in processing of auditory alerting cues. We measured electroencephalographic power and phase locking in response to alerting cues in a visual letter report task, in which younger but not older adults showed a cue-related behavioral advantage. Alerting cues evoked a significant increase in power as well as in inter-trial phase locking, with a maximum effect in the alpha frequency (8-12 Hz) in both age groups. Importantly, these cue-related increases in phase locking and power were stronger in older than in younger adults and were negatively corr...
Source: Neurobiology of Aging - April 1, 2019 Category: Geriatrics Authors: Wiegand I, Sander MC Tags: Neurobiol Aging Source Type: research

Quantitative assessment of the intracranial vasculature in an older adult population using iCafe.
Abstract Comprehensive quantification of intracranial artery features may help us assess and understand variations of blood supply during brain development and aging. We analyzed vasculature features of 163 participants (age 56-85 years, mean of 71) from a community study to investigate if any of the features varied with age. Three-dimensional time-of-flight magnetic resonance angiography images of these participants were processed in IntraCranial artery feature extraction technique (a recently developed technique to obtain quantitative features of arteries) to divide intracranial vasculatures into anatomical segm...
Source: Neurobiology of Aging - March 28, 2019 Category: Geriatrics Authors: Chen L, Sun J, Hippe DS, Balu N, Yuan Q, Yuan I, Zhao X, Li R, He L, Hatsukami TS, Hwang JN, Yuan C Tags: Neurobiol Aging Source Type: research

Reduced memory-related ongoing oscillatory activity in healthy older adults.
Abstract Age-related impairments in episodic memory have been linked to alterations in encoding-induced neural activity. In young individuals, even prestimulus activity has been shown to influence the encoding of an upcoming stimulus, with ongoing theta and beta oscillations being predictive of subsequent recognition. The present study investigated if these memory-related ongoing oscillations are also affected by aging. In an EEG experiment, healthy older and young individuals performed an encoding task with a subsequent recognition test on picture and word stimuli. The group of younger participants showed an incr...
Source: Neurobiology of Aging - March 27, 2019 Category: Geriatrics Authors: Winterling SL, Shields SM, Rose M Tags: Neurobiol Aging Source Type: research

Modulation of miR-34a/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis.
Abstract Mitophagy and mitochondrial biogenesis are 2 pathways that regulate mitochondrial content and metabolism maintaining cellular homeostasis. The imbalance between these opposing processes impairs mitochondrial function and is suggested to be the pathophysiological basis of a variety of neurodegenerative diseases and aging. Here we investigated the role of mitophagy and mitochondrial biogenesis in oxidative damage to the cochlear hair cells and age-related hearing loss. In cultured mouse House Ear Institute-Organ of Corti 1 hair cells, oxidative stress activated mitophagy but inhibited mitochondrial biogenes...
Source: Neurobiology of Aging - March 27, 2019 Category: Geriatrics Authors: Xiong H, Chen S, Lai L, Yang H, Xu Y, Pang J, Su Z, Lin H, Zheng Y Tags: Neurobiol Aging Source Type: research