Corrigendum to "Transcriptional alterations in skin fibroblasts from Parkinson's disease patients with parkin mutations" [Neurobiol. Aging 65 (2018) 206-216].
Corrigendum to "Transcriptional alterations in skin fibroblasts from Parkinson's disease patients with parkin mutations" [Neurobiol. Aging 65 (2018) 206-216]. Neurobiol Aging. 2018 Sep;69:300 Authors: PMID: 30053994 [PubMed - in process] (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - August 2, 2018 Category: Geriatrics Tags: Neurobiol Aging Source Type: research

Differential expression of synaptic and interneuron genes in the aging human prefrontal cortex.
Abstract Altered inhibition-excitation balance is implicated in brain aging. We hypothesized that expression of 14 genes encoding proteins localized to synapses or interneurons would show age-related changes relative to 1 another in postmortem tissue from the prefrontal cortex of 37 individuals (18-78 years) and that synaptic or interneuron markers would be differentially correlated with human brain volumes across aging. The majority of genes examined were differentially expressed with age, most being downregulated. Expression of 3 interneuron-related genes was significantly negatively associated with age (calbind...
Source: Neurobiology of Aging - July 18, 2018 Category: Geriatrics Authors: Mohan A, Thalamuthu A, Mather KA, Zhang Y, Catts VS, Weickert CS, Sachdev PS Tags: Neurobiol Aging Source Type: research

Lifestyle activities in mid-life contribute to cognitive reserve in late-life, independent of education, occupation, and late-life activities.
In conclusion, MAs contribute uniquely to CR. The modifiability of these activities has implications for public health initiatives aimed at dementia prevention. PMID: 30025291 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - July 16, 2018 Category: Geriatrics Authors: Chan D, Shafto M, Kievit R, Matthews F, Spink M, Valenzuela M, Cam-CAN, Henson RN Tags: Neurobiol Aging Source Type: research

Novel VCP mutations expand the mutational spectrum of frontotemporal dementia.
Le Ber I Abstract Valosin-containing protein (VCP) mutations are rare causes of autosomal dominant frontotemporal dementias associated with Paget's disease of bone, inclusion body myopathy, and amyotrophic lateral sclerosis. We analyzed the VCP gene in a cohort of 199 patients with frontotemporal dementia and identified 7 heterozygous mutations in unrelated families, including 3 novel mutations segregating with dementia. This expands the VCP mutation spectrum and suggests that although VCP mutations are rare (3.5% in this study), the gene should be analyzed even in absence of the full syndromic complex. Reporting...
Source: Neurobiology of Aging - June 30, 2018 Category: Geriatrics Authors: Saracino D, Clot F, Camuzat A, Anquetil V, Hannequin D, Guyant-Maréchal L, Didic M, Guillot-Noël L, Rinaldi D, Latouche M, Forlani S, Ghassab Y, Coppola C, Di Iorio G, David I, French research network on FTD/FTD-ALS, Le Guern E, Brice A, Le Ber I Tags: Neurobiol Aging Source Type: research

Aging-associated changes in cerebral vasculature and blood flow as determined by quantitative optical coherence tomography angiography.
Abstract Normal aging is associated with significant alterations in brain's vascular structure and function, which can lead to compromised cerebral circulation and increased risk of neurodegeneration. The in vivo examination of cerebral blood flow (CBF), including capillary beds, in aging brains with sufficient spatial detail remains challenging with current imaging modalities. In the present study, we use 3-dimensional (3-D) quantitative optical coherence tomography angiography (OCTA) to examine characteristic differences of the cerebral vasculatures and hemodynamics at the somatosensory cortex between old (...
Source: Neurobiology of Aging - June 22, 2018 Category: Geriatrics Authors: Li Y, Choi WJ, Wei W, Song S, Zhang Q, Liu J, Wang RK Tags: Neurobiol Aging Source Type: research

No association of salivary total tau concentration with Alzheimer's disease.
In this study, we quantified salivary total tau (t-tau) concentration in 160 healthy elderly control, 68 mild cognitive impairment, and 53 AD participants using ultrasensitive Single molecule array (Simoa) technology. No median difference in salivary t-tau concentration was found between AD and mild cognitive impairment or healthy elderly control (12.3 ng/L, 9.8 ng/L and 9.6 ng/L, respectively, p = 0.219). In addition, there was no association of salivary t-tau concentration with neurophysiological assessment or structural magnetic resonance imaging. Despite a nominal increase in AD, due to the large ov...
Source: Neurobiology of Aging - June 20, 2018 Category: Geriatrics Authors: Ashton NJ, Ide M, Schöll M, Blennow K, Lovestone S, Hye A, Zetterberg H Tags: Neurobiol Aging Source Type: research

Frequency and amplitude modulation of resting-state fMRI signals and their functional relevance in normal aging.
Abstract The intrinsic composition and functional relevance of resting-state blood oxygen level-dependent signals are fundamental in research using functional magnetic resonance imaging (fMRI). Using the Hilbert-Huang Transform to estimate high-resolution time-frequency spectra, we investigated the instantaneous frequency and amplitude modulation of resting-state fMRI signals, as well as their functional relevance in a large normal-aging cohort (n = 420, age = 21-89 years). We evaluated the cognitive function of each participant and recorded respiratory signals during fMRI scans. The results showed ...
Source: Neurobiology of Aging - June 15, 2018 Category: Geriatrics Authors: Yang AC, Tsai SJ, Lin CP, Peng CK, Huang NE Tags: Neurobiol Aging Source Type: research

The temporal sequence of improved mitochondrial function on the dynamics of respiration, mobility, and cognition in aged Drosophila.
Abstract Aging is associated with mitochondrial decline and reduced adenosine triphosphate (ATP) production leading to cellular dysfunction, but this is improved by long-wavelength light absorbed by cytochrome c oxidase, increasing cytochrome c oxidase activity, ATP production and improving metabolism, sensory motor function, and cognition. Yet, the sequence of these events is unknown. We give old flies a single 90-minute 670-nm pulse and measure temporal sequences of changes in respiration, ATP, motor, and cognitive ability. Respiration increased significantly 20 minutes after light initiation and remained e...
Source: Neurobiology of Aging - June 14, 2018 Category: Geriatrics Authors: Weinrich TW, Hogg C, Jeffery G Tags: Neurobiol Aging Source Type: research

Acute psychosocial stress in mid-aged male rats causes hyperthermia, cognitive decline, and increased deep sleep power, but does not alter deep sleep duration.
Abstract Aging is associated with altered sleep architecture and worsened hippocampus-dependent cognition, highly prevalent clinical conditions that detract from quality of life for the elderly. Interestingly, exposure to psychosocial stress causes similar responses in young subjects, suggesting that age itself may act as a stressor. In prior work, we demonstrated that young animals show loss of deep sleep, deficits in cognition, and elevated body temperature after acute stress exposure, whereas aged animals are hyporesponsive on these measures. However, it is unclear if these age-altered stress responses occur in...
Source: Neurobiology of Aging - June 14, 2018 Category: Geriatrics Authors: Hargis K, Buechel HM, Popovic J, Blalock EM Tags: Neurobiol Aging Source Type: research

Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models.
Abstract β-Amyloid oligomers (AβOs) and neuroinflammation are 2 main culprits to counteract in Alzheimer's disease (AD). Doxycycline (DOXY) is a second generation antibiotic of the tetracycline class that are promising drugs tested in many clinical trials for a number of different pathologies. DOXY is endowed with antiamyloidogenic properties and better crosses the blood-brain barrier, but its efficacy has never been tested in AD mice. We herein show that 15- to 16-month-old APP/PS1dE9 (APP/PS1) AD mice receiving DOXY under different treatment regimens recovered their memory without plaque reduction. An ...
Source: Neurobiology of Aging - June 12, 2018 Category: Geriatrics Authors: Balducci C, Santamaria G, La Vitola P, Brandi E, Grandi F, Viscomi AR, Beeg M, Gobbi M, Salmona M, Ottonello S, Forloni G Tags: Neurobiol Aging Source Type: research

An isoform-selective p38 α mitogen-activated protein kinase inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer's disease.
An isoform-selective p38α mitogen-activated protein kinase inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer's disease. Neurobiol Aging. 2018 Jun 12;70:86-91 Authors: Rutigliano G, Stazi M, Arancio O, Watterson DM, Origlia N Abstract Neuroinflammation is a fundamental mechanism in Alzheimer's disease (AD) progression. The stress-induced activation of the p38α mitogen-activated protein kinase (MAPK) leads to increased production of proinflammatory cytokines and neurodegeneration. We investigated the effects of an isoform selective p38α MAPK inhibitor...
Source: Neurobiology of Aging - June 12, 2018 Category: Geriatrics Authors: Rutigliano G, Stazi M, Arancio O, Watterson DM, Origlia N Tags: Neurobiol Aging Source Type: research

Enhanced postsynaptic inhibitory strength in hippocampal principal cells in high-performing aged rats.
Abstract Hyperactivity within the hippocampal formation, frequently observed in aged individuals, is thought to be a potential contributing mechanism to the memory decline often associated with aging. Consequently, we evaluated the postsynaptic strength of excitatory and inhibitory synapses in the granule cells of the dentate gyrus and CA1 pyramidal cells of a rat model of aging, in which each individual was behaviorally characterized as aged impaired (AI) or aged unimpaired (AU, with performance comparable to young (Y) individuals). In hippocampal slices of these 3 aged groups (Y, AI, AU), we found that compared ...
Source: Neurobiology of Aging - June 12, 2018 Category: Geriatrics Authors: Tran T, Gallagher M, Kirkwood A Tags: Neurobiol Aging Source Type: research

Doxycycline counteracts neuroinflammation restoring memory in Alzheimer ’s disease mouse models
β-amyloid oligomers (AβOs) and neuroinflammation are two main culprits to counteract in Alzheimer’s disease (AD). Doxycycline (DOXY) is a second generation antibiotic of the tetracycline class which are promising drugs tested in many clinical trials for a number of different pathologies. DOXY is endowed with anti-amyloidogenic properties and better crosses the blood-brain barrier, but its efficacy has never been tested in AD mice. We herein show that 15-16 months old APP/PS1dE9 (APP/PS1) AD mice receiving DOXY under different treatment regimens recovered their memory without plaque reducti on. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 12, 2018 Category: Neuroscience Authors: Claudia Balducci, Giulia Santamaria, Pietro La Vitola, Edoardo Brandi, Federica Grandi, Arturo Roberto Viscomi, Marten Beeg, Marco Gobbi, Mario Salmona, Simone Ottonello, Gianluigi Forloni Source Type: research

An isoform-selective p38 αMAPK inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer’s disease
Neuroinflammation is a fundamental mechanism in Alzheimer ’s disease (AD) progression. The stress-induced activation of the p38α mitogen-activated protein kinase (MAPK) leads to increased production of proinflammatory cytokines and neurodegeneration. We investigated the effects of an isoform selective p38α MAPK inhibitor, MW01-18-150SRM (MW150), admini stered at 2.5 mg/kg/day ( i.p.; 14 days) on early entorhinal cortex (EC) alterations in an AD mouse model carrying human mutations of amyloid precursor protein (mhAPP): We used electrophysiological analyses with LTP induction in EC-containing brain slices a...
Source: Neurobiology of Aging - June 12, 2018 Category: Neuroscience Authors: Grazia Rutigliano, Martina Stazi, Ottavio Arancio, D. Martin Watterson, Nicola Origlia Tags: Brief communication Source Type: research

Frequency and Amplitude Modulation of Resting-State fMRI Signals and Their Functional Relevance in Normal Aging
The intrinsic composition and functional relevance of resting-state blood oxygen level dependent (BOLD) signals are fundamental in research using functional magnetic resonance imaging (fMRI). Using the Hilbert –Huang Transform (HHT) to estimate high-resolution time-frequency spectra, we investigated the instantaneous frequency and amplitude modulation of resting-state fMRI signals, as well as their functional relevance in a large normal-aging cohort (n = 420, age = 21–89 years). We evaluated the cogni tive function of each participant, and recorded respiratory signals during fMRI scans. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 12, 2018 Category: Neuroscience Authors: Albert C. Yang, Shih-Jen Tsai, Ching-Po Lin, Chung-Kang Peng, Norden E. Huang Source Type: research

Enhanced Postsynaptic Inhibitory Strength In Hippocampcl Principal Cells In High Performing Aged Rats
Hyperactivity within the hippocampal formation, frequently observed in aged individuals, is thought to be a potential contributing mechanism to the memory decline often associated with aging. Consequently, we evaluated the postsynaptic strength of excitatory and inhibitory synapses in the granule cells of the dentate gyrus and CA1 pyramidal cells of a rat model of aging, in which each individual was behaviorally characterized as aged impaired (AI) or aged unimpaired (AU, with performance comparable to young (Y) individuals. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 12, 2018 Category: Neuroscience Authors: Trinh Tran, Michela Gallagher, Alfredo Kirkwood Source Type: research

Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged  rats.
Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats. Neurobiol Aging. 2018 Jun 11;70:102-116 Authors: Zhou YF, Li PC, Wu JH, Haslam JA, Mao L, Xia YP, He QW, Wang XX, Lei H, Lan XL, Miao QR, Yue ZY, Li YN, Hu B Abstract Brain tissue survival and functional recovery after ischemic stroke greatly depend on cerebral vessel perfusion and functional collateral circulation in the ischemic area. Semaphorin 3E (Sema3E), one of the class 3 secreted semaphorins, has been demonstrated to be a critical regulator in embr...
Source: Neurobiology of Aging - June 11, 2018 Category: Geriatrics Authors: Zhou YF, Li PC, Wu JH, Haslam JA, Mao L, Xia YP, He QW, Wang XX, Lei H, Lan XL, Miao QR, Yue ZY, Li YN, Hu B Tags: Neurobiol Aging Source Type: research

The effects of cerebral amyloid angiopathy on integrity of the blood-brain barrier.
Abstract Cerebral amyloid angiopathy (CAA), in which amyloid accumulates predominantly in the walls of arterioles and capillaries, is seen in most patients with Alzheimer disease (AD) and may contribute to compromise of blood-brain barrier (BBB) function seen in AD. We investigated the effects of CAA on BBB integrity by examining the expression of the endothelial marker CD31, basement membrane protein collagen IV (COL4), tight junction protein claudin-5, and fibrinogen, a marker of BBB leakage, by immunohistochemistry in the occipital cortex of autopsy brains with AD and capillary CAA (CAA type 1; n = 8), AD ...
Source: Neurobiology of Aging - June 11, 2018 Category: Geriatrics Authors: Magaki S, Tang Z, Tung S, Williams CK, Lo D, Yong WH, Khanlou N, Vinters HV Tags: Neurobiol Aging Source Type: research

Sema3E/PlexinD1 Inhibition is a Therapeutic Strategy for Improving Cerebral Perfusion and Restoring Functional Loss after Stroke in Aged Rats
Brain tissue survival and functional recovery following ischaemic stroke greatly depend on cerebral vessel perfusion and functional collateral circulation in the ischaemic area. Semaphorin 3E (Sema3E), one of the class 3 secreted semaphorins, has been demonstrated to be a critical regulator in embryonic and postnatal vascular formation via binding to its receptor PlexinD1. However, whether Sema3E/PlexinD1 signalling is involved in poststroke neovascularization remains unknown. To determine the contribution of Sema3E/PlexinD1 signalling to poststroke recovery, aged rats (18 months) were subjected to a transient middle cereb...
Source: Neurobiology of Aging - June 11, 2018 Category: Neuroscience Authors: Yi-Fan Zhou, Peng-Cheng Li, Jie-Hong Wu, James Andrew Haslam, Ling Mao, Yuan-Peng Xia, Quan-Wei He, Xu-Xia Wang, Hao Lei, Xiao-Li Lan, Qing Robert Miao, Zhen-Yu Yue, Ya-Nan Li, Bo Hu Source Type: research

The effects of cerebral amyloid angiopathy on integrity of the blood brain barrier
Cerebral amyloid angiopathy (CAA), in which amyloid accumulates predominantly in the walls of arterioles and capillaries, is seen in the majority of patients with Alzheimer disease (AD) and may contribute to compromise of blood brain barrier (BBB) function seen in AD. We investigated the effects of CAA on BBB integrity by examining the expression of the endothelial marker CD31, basement membrane protein collagen IV (COL4), tight junction protein claudin-5, and fibrinogen, a marker of BBB leakage, by immunohistochemistry in the occipital cortex of autopsy brains with AD and capillary CAA (CAA type 1; n = 8), AD with non-cap...
Source: Neurobiology of Aging - June 11, 2018 Category: Neuroscience Authors: Shino Magaki, Zhaoyi Tang, Spencer Tung, Christopher K. Williams, Darrick Lo, William H. Yong, Negar Khanlou, Harry V. Vinters Source Type: research

Estimates of Age-related Memory Decline are Inflated by Unrecognized Alzheimer ’s disease
This study aimed to determine the extent to which estimates of cognitive aging were biased by preclinical AD. Cognitively normal older adults (n = 494) with amyloid-β status determined from PET neuroimaging underwent serial neuropsychological assessment at 18-month intervals over 72-months. Estimates of the effects of age on verbal memory, working memory, executive function, and processing speed were derived using linear mixed models. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 11, 2018 Category: Neuroscience Authors: Karra D. Harrington, Adrian Schembri, Yen Ying Lim, Christa Dang, David Ames, Jason Hassenstab, Simon M. Laws, Stephanie Rainey-Smith, Joanne Robertson, Christopher C. Rowe, Hamid R. Sohrabi, Olivier Salvado, Michael Weinborn, Victor L. Villemagne, Colin Source Type: research

Attentional ERPs distinguish aging and early Alzheimer's dementia.
Abstract The early detection of Alzheimer's disease requires our distinguishing it from cognitive aging. Here, we test whether spatial attentional changes might support that distinction. We engaged young normal (YN), older normal (ON), and patients with early Alzheimer's dementia (EAD) in an attentionally cued, self-movement heading discrimination task while we recorded push-button response times and event related potentials. YNs and ONs show the behavioral effects of attentional shifts from the cue to the target, whereas EAD patients did not (p
Source: Neurobiology of Aging - June 6, 2018 Category: Geriatrics Authors: Lockwood CT, Vaughn W, Duffy CJ Tags: Neurobiol Aging Source Type: research

Attentional ERPs Distinguish Aging and Early Alzheimer ’s Dementia
The early detection of Alzheimer ’s disease requires our distinguishing it from cognitive aging. Here we test whether spatial attentional changes might support that distinction. We engaged young (YN) and older (ON) normals, and patients with early Alzheimer’s dementia (EAD) in an attentionally cued, self-movement heading discri mination task while we recorded push-button RTs and ERPs. YNs and ONs show the behavioral effects of attentional shifts from the cue to the target, whereas EADs did not (p (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 6, 2018 Category: Neuroscience Authors: Colin T. Lockwood, William Vaughn, Charles J. Duffy Source Type: research

Cover 2: Editorial Advisory Board
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 5, 2018 Category: Neuroscience Source Type: research

Contents Continued
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 5, 2018 Category: Neuroscience Source Type: research

Cover 4: Contents
(Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 5, 2018 Category: Neuroscience Source Type: research

Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance.
Abstract The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase [OGT]) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the uridine-diphosphate-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins. This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and plays an important role in regulating cellular signaling, transcription, and metabolism. However, little is known about the function of OGT in the brain. Here, we report th...
Source: Neurobiology of Aging - June 4, 2018 Category: Geriatrics Authors: Dai CL, Gu JH, Liu F, Iqbal K, Gong CX Tags: Neurobiol Aging Source Type: research

Neuronal O-GlcNAc transferase regulates appetite, body weight, and peripheral insulin resistance
The ogt gene encodes O-linked N-acetylglucosamine transferase (O-GlcNAc transferase, OGT) that catalyzes the transfer of β-N-acetylglucosamine (GlcNAc) from the UDP-GlcNAc to the hydroxyl group of serine or threonine residues of nucleocytoplasmic proteins. This process is a common protein posttranslational modification, called protein O-GlcNAcylation, which is a known intracellular sensor of glucose metabolism and pl ays an important role in regulating cellular signaling, transcription and metabolism. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - June 4, 2018 Category: Neuroscience Authors: Chun-ling Dai, Jin-hua Gu, Fei Liu, Khalid Iqbal, Cheng-Xin Gong Source Type: research

Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies.
g S Abstract 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 0.021 unit increase (95% confidence inte...
Source: Neurobiology of Aging - June 2, 2018 Category: Geriatrics Authors: Zhan Y, Clements MS, Roberts RO, Vassilaki M, Druliner BR, Boardman LA, Petersen RC, Reynolds CA, Pedersen NL, Hägg S Tags: Neurobiol Aging Source Type: research

A simple and clinically relevant combination of neuroimaging and functional indexes for the identification of those at highest risk of Alzheimer's disease.
Abstract 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. The findings ...
Source: Neurobiology of Aging - June 1, 2018 Category: Geriatrics Authors: Tabatabaei-Jafari H, Walsh E, Shaw ME, Cherbuin N, Alzheimer's Disease Neuroimaging Initiative (ADNI) Tags: Neurobiol Aging Source Type: research

Levels of retinal IAPP are altered in Alzheimer's disease patients and correlate with vascular changes and hippocampal IAPP levels.
m M Abstract 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. ...
Source: Neurobiology of Aging - June 1, 2018 Category: Geriatrics Authors: Schultz N, Byman E, Netherlands Brain Bank, Wennström M Tags: Neurobiol Aging Source Type: research

Clinical features and genetic characterization of two dizygotic twins with C9orf72 expansion.
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. The described cases presented an overlapping phenoty...
Source: Neurobiology of Aging - June 1, 2018 Category: Geriatrics Authors: Conforti FL, Tortelli R, Morello G, Capozzo R, Barulli MR, Cavallaro S, Logroscino G Tags: Neurobiol Aging Source Type: research

The hippocampal longitudinal axis – relevance for underlying tau and TDP-43 pathology?
Recent studies suggest that hippocampus has different cortical connectivity and functionality along its longitudinal axis. We sought to elucidate the possible different pattern of atrophy in longitudinal axis of hippocampus between Amyloid/Tau pathology and TDP-43-pathies.Seventy-three presenile subjects were included: Amyloid/Tau group (33 Alzheimer ’s disease (AD) with confirmed CSF biomarkers), probable TDP-43 group (7 semantic variant progressive primary aphasia, 5 GRN and 2 C9orf72 mutation carriers) and 26 healthy controls. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 31, 2018 Category: Neuroscience Authors: Albert Llado, Adri à Tort-Merino, Raquel Sanchez-Valle, Neus Falgas, Mircea Balasa, Bea Bosch, Magda Castellvi, Jaume Olives, Anna Antonell, Michael Hornberger Source Type: research

Do diurnal cortisol levels mediate the association between sleep disturbances and cognitive impairment?
Abstract 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. Subjects ...
Source: Neurobiology of Aging - May 30, 2018 Category: Geriatrics Authors: Haba-Rubio J, Ouanes S, Franc Y, Marques-Vidal P, Waeber G, Vollenweider P, von Gunten A, Preisig M, Kuehner C, Castelao E, Heinzer R, Popp J Tags: Neurobiol Aging Source Type: research

Watershed Microinfarct Pathology and Cognition in Older Persons
Brain microinfarcts are common in aging and are associated with cognitive impairment. Anterior and posterior watershed border zones lie at the territories of the anterior, middle, and posterior cerebral arteries, and are more vulnerable to hypoperfusion than brain regions outside the watershed regions. However, little is known about microinfarcts in these regions and how they relate to cognition in aging. Participants from the Rush Memory and Aging Project (MAP), a community-based clinical-pathologic study of aging, underwent detailed annual cognitive evaluations. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: A. Kapasi, S.E. Leurgans, B.D. James, P.A. Boyle, Z. Arvanitakis, S. Nag, D.A. Bennett, A.S. Buchman, J.A. Schneider Source Type: research

The contribution of small vessel disease to subtypes of Alzheimer ’s disease: a study on cerebrospinal fluid and imaging biomarkers
We investigated whether subtypes of Alzheimer ’s disease (AD), i.e. typical, limbic-predominant, hippocampal-sparing, and minimal atrophy AD, had a specific signature of small vessel disease and neurodegeneration. 423 clinically diagnosed AD patients were included (161 typical, 121 limbic-predominant, 70 hippocampal-sparing, 71 minimal atroph y). 156 fulfilled a biomarkers-based AD diagnosis. White matter hyperintensities (WMH) and cerebral microbleeds (CMB) had the highest prevalence in limbic-predominant AD, and the lowest prevalence in minimal atrophy AD. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: Daniel Ferreira, Sara Shams, Lena Cavallin, Matti Viitanen, Juha Martola, Tobias Granberg, Mana Shams, Peter Aspelin, Maria Kristoffersen-Wiberg, Agneta Nordberg, Lars-Olof Wahlund, Eric Westman Source Type: research

Longitudinal serum S100 β and brain ageing in the Lothian Birth Cohort 1936
Elevated serum and cerebrospinal fluid concentrations of S100 β, a protein predominantly found in glia, are associated with intracranial injury and neurodegeneration, though concentrations are also influenced by several other factors. The longitudinal association between serum S100β concentrations and brain health in non-pathological ageing is unknown. In a large group (baseline N = 593; longitudinal N = 414) of community-dwelling older adults at ages 73 and 76 years, we examined cross-sectional and parallel longitudinal changes between serum S100β and brain MRI parameters: white matter hyperintensities (WMH...
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: Simon R. Cox, Mike Allerhand, Stuart J. Ritchie, Susana Mu ñoz Maniega, Maria Valdés Hernández, Sarah E. Harris, David Alexander Dickie, Devasuda Anblagan, Benjamin S. Aribisala, Zoe Morris, Roy Sherwood, N. Joan Abbott, John M. Starr, Mark E. Bastin, Source Type: research

Diagnostic Consistency of Cases from ADNI Cohort Meta-Data: Methodological Considerations
ADNI has established the gold standard for the development and formalization of methodologies for investigating neuroimaging, genetic and blood biomarkers for the study of AD, MCI and the healthy aging brain (Weiner et al., 2015). Since 2004, ADNI has i) developed standardized biomarkers for use in clinical trial subject selection and for proxy outcome measures; ii) provided uniform neuroimaging protocols for use in multi-center trials; iii) initiated a global network of ADNI sites as well as international brain disease research programs based upon the ADNI model; iv) spawned affiliated programs investigating traumatic bra...
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: Andrew Zywiec, R. Duncan Kirkby Tags: Letter to the editor Source Type: research

Response to Zywieck and Kirkby paper
The letter by Zywieck and Kirkby describes a perceived difficulty identifying the “contemporaneous diagnosis” at the time of a specific scan for participants of ADNI. It is important to emphasize for users of ADNI that obtaining full descriptions of all data for each participant requires careful review of the data files and documentation. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: Michael W. Weiner, Arthur Toga, Danielle Harvey, Michael Donohue, Laurel Beckett Tags: Letter to the editor Source Type: research

MicroRNA alterations in iPSC-derived dopaminergic neurons from Parkinson disease patients
MicroRNA (miRNA) misregulation in peripheral blood has been linked to Parkinson disease (PD) but its role in the disease progression remains elusive. We performed an explorative genome-wide study of miRNA expression levels in dopaminergic neurons (DAn) from PD patients generated by somatic cell reprogramming and induced pluripotent stem cells (iPSC) differentiation. We quantified expression levels of 377 miRNAs in DAn from three sporadic PD patients (sPD), three monogenic LRRK2-associated PD patients (L2PD) (total six PD), and four healthy controls. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: Eduard Tolosa, Teresa Botta-Orfila, Xavier Morat ó, Carles Calatayud, Raquel Ferrer-Lorente, María-José Martí, Manel Fernández, Carles Gaig, Ángel Raya, Antonella Consiglio, Mario Ezquerra, Rubén Fernández-Santiago Source Type: research

Guanfacine treatment for prefrontal cognitive dysfunction in elderly participants: a randomized clinical trial
This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally-mediated cognitive functions, as well as quality of life and global function in healthy elderly participants. One hundred twenty-three participants 75-years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: Nicole M. Barcelos, Peter H. Van Ness, Allison F. Wagner, Martha G. MacAvoy, Adam P. Mecca, George M. Anderson, Mark Trentalange, Keith A. Hawkins, Mary Sano, Amy F.T. Arnsten, Christopher H. van Dyck Source Type: research

Phasic alertness cues modulate visual processing speed in healthy aging
Warning signals temporarily increase the rate of visual information in younger participants and, thus, optimize perception in critical situations. It is unclear whether such important preparatory processes are preserved in healthy aging. We parametrically assessed the effects of auditory alertness cues on visual processing speed and their time course using a whole report paradigm based on the computational Theory of Visual Attention (TVA). We replicated prior findings of significant alerting benefits in younger adults. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 30, 2018 Category: Neuroscience Authors: Marleen Haupt, Christian Sorg, Natan Napi órkowski, Kathrin Finke Source Type: research

Parkinsonism is Associated with Altered Primary Motor Cortex Plasticity in Frontotemporal Dementia-PPA variant
In Frontotemporal dementia (FTD), the behavioural variant (bv-FTD) and non-fluent 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 (TMS) we investigated long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the primary motor cortex (M1) of bv-FTD and nfv-PPA patients, with and without parkinsonism, by using the theta-burst stimulation (TBS) protoco...
Source: Neurobiology of Aging - May 29, 2018 Category: Neuroscience Authors: Di Stasio Flavio, Suppa Antonio, Fabbrini Andrea, Marsili Luca, Asci Francesco, Conte Antonella, Trebbastoni Alessandro, De Lena Carlo, Berardelli Alfredo Source Type: research

Stress-related deficits of older adults ’ spatial working memory: An EEG investigation of occipital alpha and frontal-midline theta activity
This study paired electrophysiological with behavioral measures to explore how cumulative stress affects attentional and maintenance processes underpinning working memory retention. We collected electroencephalographic (EEG) 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-occiptial alpha (8 – 12 Hz) and frontal-midline theta (4 – 6 Hz) as indicators of attentional and maintenance processes. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 28, 2018 Category: Neuroscience Authors: Amanda C. Marshall, Nicholas Cooper, Livia Rosu, Steffan Kennett Source Type: research

APOE ε4 Status in Healthy Older African Americans is Associated with Deficits in Pattern Separation and Hippocampal Hyperactivation
African Americans are 1.4 times more likely than European Americans to carry the 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. Previous work using the mnemonic discrimination paradigm has localized increased activation in the DG/C...
Source: Neurobiology of Aging - May 25, 2018 Category: Neuroscience Authors: Neha Sinha, Chelsie N. Berg, Nicholas J. Tustison, Ashlee Shaw, Diane Hill, Michael A. Yassa, Mark A. Gluck Source Type: research

PDE8B mutation is not associated with Parkinson ’s disease in a Taiwanese Population
Mutations in the phosphodiesterase 8B gene (PDE8B) were recently linked to autosomal-dominant striatal degeneration clinically presenting as slowly progressive parkinsonism. PDE8B degrades cyclic AMP, 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. Among 642 participants, we sequenced the exon containing previously reported mutations and exon-intron boundaries of PDE 8B in 196 P...
Source: Neurobiology of Aging - May 25, 2018 Category: Neuroscience Authors: Tian-Sin Fan, Ruey-Meei Wu, Hang-I. Lin, Chieh Cheng, Chin-Hsien Lin Tags: Negative results Source Type: research

Curvilinear locus coeruleus functional connectivity trajectories over the adult lifespan: a 7T MRI study
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 non-linearly with age and explored its relation to memory function. To that end, forty-nine cognitively healthy individuals (19-74 years) underwent ultra high-resolution 7T resting-state fMRI and cognitive testing. FC patterns from the LC to regions of the isodendritic core network and cortical regions were examined using ROI-to-ROI analyses. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 24, 2018 Category: Neuroscience Authors: Heidi I.L. Jacobs, Lisa M üller-Ehrenberg, Nikos Priovoulos, Alard Roebroek Source Type: research

Postmortem Brain MRI Is Related to Cognitive Decline, Independent of Cerebral Vessel Disease in Older Adults
The purpose of this study was to determine whether metrics of brain tissue integrity derived from postmortem MRI are associated with late life cognitive decline, independent of cerebral vessel disease. Using data from 554 older adults, we employed 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 three indices of vessel disease: atherosclerosis, arterio...
Source: Neurobiology of Aging - May 23, 2018 Category: Neuroscience Authors: Robert J. Dawe, Lei Yu, Julie A. Schneider, Konstantinos Arfanakis, David A. Bennett, Patricia A. Boyle Source Type: research

Functional Networks Underlying Item and Source Memory: Shared and Distinct Network Components and Age-Related Differences
Whereas the medial temporal lobes (MTL) are critical for both item memory (IM) and source memory (SM), lateral prefrontal cortex (LatPFC) and posterior parietal cortex (PPC) play a greater role during SM than IM. It is unclear, however, how these differences translate into shared and distinct IM vs. 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. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 21, 2018 Category: Neuroscience Authors: Zachary A. Monge, Matthew L. Stanley, Benjamin R. Geib, Simon W. Davis, Roberto Cabeza Source Type: research

The effect of APOE genotype on Alzheimer ’s disease risk is influenced by sex and DHA status
An 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. (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - May 21, 2018 Category: Neuroscience Authors: Matthew Pontifex, David Vauzour, Anne-Marie Minihane Source Type: research