Confirmation of high frequency of C9orf72 mutations in patients with frontotemporal dementia from Sweden.
berg H, Graff C Abstract Frontotemporal dementia (FTD) is the second most common early-onset dementia. Up to half of the cases are familial, and several mutations have been identified as pathogenic. Repeat expansion mutations in C9orf72 are the most common genetic cause of FTD and are particularly frequent in Sweden and Finland. We aimed to determine the mutation frequency in patients with FTD ascertained at a memory clinic in Sweden and assess the inheritance pattern in the families. We screened 132 patients with FTD for mutations in C9orf72, GRN, and MAPT, and the frequency was 34.1%. Two novel variations, not p...
Source: Neurobiology of Aging - March 27, 2019 Category: Geriatrics Authors: Öijerstedt L, Chiang HH, Björkström J, Forsell C, Lilius L, Lindström AK, Thonberg H, Graff C Tags: Neurobiol Aging Source Type: research

Association study of rs3846662 with Alzheimer's disease in a population-based cohort: the Cache County Study.
Abstract 3-Hydroxy-3-methylglutaryl coenzyme A reductase is associated with monitoring cholesterol levels. The presence of the single-nucleotide polymorphism rs3846662 introduces alternative splicing at exon 13; the exclusion of this exon leads to a reduction in total cholesterol levels. Lower cholesterol levels are linked to a reduction in Alzheimer's disease (AD) risk. The major allele of rs3846662, which encourages the splicing of exon 13, has recently been shown to act as a preventative allele for AD, especially in women. The purpose of our research was to replicate and confirm this finding. Using logistic reg...
Source: Neurobiology of Aging - March 15, 2019 Category: Geriatrics Authors: Wright SM, Jensen SL, Cockriel KL, Davis B, Tschanz JT, Munger RG, Corcoran CD, Kauwe JSK Tags: Neurobiol Aging Source Type: research

Population-based genome-wide association study of cognitive decline in older adults free of dementia: identification of a novel locus for the attention domain.
Abstract To identify novel loci that affect cognitive decline in older adults free of dementia, we conducted genome-wide and gene-based meta-analyses on longitudinal slopes of 5 cognitive domains (memory, executive function, language, attention/processing speed, and visuospatial ability) derived from 2 population-based cohorts. For decline over time in each cognitive domain, we normalized intraindividual slopes within each cohort, accounting for baseline age, sex, and years of education. Normalized slope for each domain was used in cohort-specific genome-wide analyses after including top principal components as co...
Source: Neurobiology of Aging - March 11, 2019 Category: Geriatrics Authors: Kamboh MI, Fan KH, Yan Q, Beer JC, Snitz BE, Wang X, Chang CH, Demirci FY, Feingold E, Ganguli M Tags: Neurobiol Aging Source Type: research

Genetic analysis of DNA methylation and hydroxymethylation genes in Parkinson's disease.
Abstract DNA methylation is an important regulatory mechanism of Parkinson's disease (PD). To investigate the relationship between DNA methylation and hydroxymethylation genes and PD, we performed gene-targeted sequencing using molecular inversion probes in a Chinese PD population. We sequenced 12 genes related to DNA methylation and hydroxymethylation in 1657 patients and 1394 control subjects. We conducted genewise association analyses of rare variants detected in the present study and identified the TET1 gene as important in PD (p = 0.0037738, 0.013, 0.019521 (b.collapse test, variable threshold test, and ...
Source: Neurobiology of Aging - March 11, 2019 Category: Geriatrics Authors: Shu L, Qin L, Min S, Pan H, Zhong J, Guo J, Sun Q, Yan X, Chen C, Tang B, Xu Q Tags: Neurobiol Aging Source Type: research

Mild cognitive impairment reverters have a favorable cognitive prognosis and cortical integrity in Parkinson's disease.
This study aimed to investigate whether reversion to cognitively normal status (CogN) is related to a favorable cognitive prognosis in Parkinson's disease with mild cognitive impairment (PD-MCI). We recruited 217 patients with PD-MCI who underwent serial neuropsychological assessments 3-5 times (mean interval, 1.84 years). Thirty-six patients reverted to CogN (reverters) during follow-up, whereas the other 181 did not (nonreverters). We assessed the risk of cognitive worsening in PD-MCI reverters, nonreverters, and patients with PD-CogN (n = 88). In addition, we performed comparative analyses of comprehensive neu...
Source: Neurobiology of Aging - March 11, 2019 Category: Geriatrics Authors: Chung SJ, Park YH, Yoo HS, Lee YH, Ye BS, Sohn YH, Lee JM, Lee PH Tags: Neurobiol Aging Source Type: research

Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome.
er MQ Abstract There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (≥30 years of age), divided into 3 groups by diagnosis-stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apat...
Source: Neurobiology of Aging - March 11, 2019 Category: Geriatrics Authors: Fonseca LM, Mattar GP, Haddad GG, Gonçalves AS, Miguel AQC, Guilhoto LM, Zaman S, Holland AJ, Bottino CMC, Hoexter MQ Tags: Neurobiol Aging Source Type: research

Associations between baseline amyloid, sex, and APOE on subsequent tau accumulation in cerebrospinal fluid.
Abstract We investigated the effect of baseline Aβ, sex, and APOE on longitudinal tau accumulation in cerebrospinal fluid (CSF) in clinically normal older adults. Two hundred thirty-nine participants (aged 56-89 years, clinical dementia rating = 0) underwent serial CSF collection for Aβ1-42, total-tau (t-tau) and phospho-tau181P (p-tau). We used preprocessed data from fully automated Roche Elecsys immunoassays. A series of linear regressions were used to examine cross-sectional effects of Aβ1-42, sex, and APOEε4 on baseline CSF tau and linear mixed models for longitudinal chan...
Source: Neurobiology of Aging - March 7, 2019 Category: Geriatrics Authors: Buckley RF, Mormino EC, Chhatwal J, Schultz AP, Rabin JS, Rentz DM, Acar D, Properzi MJ, Dumurgier J, Jacobs H, Gomez-Isla T, Johnson KA, Sperling RA, Hanseeuw BJ, Alzheimer's Disease Neuroimaging Initiative Tags: Neurobiol Aging Source Type: research

Whole exome should be preferred over Sanger sequencing in suspected mitochondrial myopathy.
PMID: 30933818 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - March 1, 2019 Category: Geriatrics Authors: Finsterer J Tags: Neurobiol Aging Source Type: research

Intelligence moderates the relationship between age and inter-connectivity of resting state networks in older adults.
Abstract Age-related changes in the interactive behavior of default mode network (DMN) with other resting state networks are poorly understood. We hypothesized that age would positively correlate with inter-network connectivity in late life and intellectual functioning was expected to moderate this relationship. The sample consisted of 48 community-dwelling older adults with resting state functional magnetic resonance imaging data. Global inter-connectivity between DMN and 9 other resting state networks was calculated using a novel computational framework based on machine learning. Intellectual functioning (intell...
Source: Neurobiology of Aging - February 27, 2019 Category: Geriatrics Authors: Lindbergh CA, Zhao Y, Lv J, Mewborn CM, Puente AN, Terry DP, Renzi-Hammond LM, Hammond BR, Liu T, Miller LS Tags: Neurobiol Aging Source Type: research

Sleep EEG functional connectivity varies with age and sex, but not general intelligence.
In this study of 172 healthy individuals (17-69 years old), we show that functional connectivity between distant brain areas-reflected by the weighted phase lag index of the sleep EEG-is strongly affected by the age and sex of participants. Both NREM and REM connectivity in the theta and beta range increased with age, whereas a decrease was seen in the sigma range. Connectivity was substantially greater in females than in males in the high sigma frequency range, but an opposite pattern was seen in the alpha/low sigma and beta range. General intelligence was not significantly associated with connectivity in either sex....
Source: Neurobiology of Aging - February 21, 2019 Category: Geriatrics Authors: Ujma PP, Konrad BN, Simor P, Gombos F, Körmendi J, Steiger A, Dresler M, Bódizs R Tags: Neurobiol Aging Source Type: research

Delayed daily activity and reduced NREM slow-wave power in the APPswe/PS1dE9 mouse model of Alzheimer's disease.
Abstract Alzheimer's disease (AD) is associated with disrupted circadian rhythms and sleep, which are thought to reflect an impairment of internal circadian timekeeping that contribute to clinical symptoms and disease progression. To evaluate these hypotheses, a suitable preclinical model of AD is needed. We performed a comprehensive assessment of circadian rhythms and sleep in the APPswe/PS1dE9 (APP/PS1) mouse model using long-term in vivo electroencephalogram (EEG) monitoring and behavioral assays from 5 to 22 months of age. APP/PS1 mice were crossed with a PERIOD2::LUCIFERASE (PER2::LUC) mouse model t...
Source: Neurobiology of Aging - February 14, 2019 Category: Geriatrics Authors: Kent BA, Michalik M, Marchant EG, Yau KW, Feldman HH, Mistlberger RE, Nygaard HB Tags: Neurobiol Aging Source Type: research

Age-related decrease in cortical excitability circadian variations during sleep loss and its links with cognition.
Abstract Cortical excitability depends on sleep-wake regulation, is central to cognition, and has been implicated in age-related cognitive decline. The dynamics of cortical excitability during prolonged wakefulness in aging are unknown, however. Here, we repeatedly probed cortical excitability of the frontal cortex using transcranial magnetic stimulation and electroencephalography in 13 young and 12 older healthy participants during sleep deprivation. Although overall cortical excitability did not differ between age groups, the magnitude of cortical excitability variations during prolonged wakefulness was dampened...
Source: Neurobiology of Aging - February 13, 2019 Category: Geriatrics Authors: Gaggioni G, Ly JQM, Muto V, Chellappa SL, Jaspar M, Meyer C, Delfosse T, Vanvinckenroye A, Dumont R, Coppieters 't Wallant D, Berthomier C, Narbutas J, Van Egroo M, Luxen A, Salmon E, Collette F, Phillips C, Schmidt C, Vandewalle G Tags: Neurobiol Aging Source Type: research

Interaction of nutrition and genetics via DNMT3L-mediated DNA methylation determines cognitive decline.
Abstract Low homocysteine levels and B vitamin treatment are reported to protect against declining cognitive health. Both B vitamins and homocysteine are involved in the production of S-adenosylmethionine, a universal methyl donor essential for the process of DNA methylation. We investigated the effect of a damaging coding variant within the DNA methyltransferase gene DNMT3L (R278G, A/G) by examining B vitamin intake, homocysteine levels, cognitive performance, and brain atrophy in individuals in the VITACOG study of mild cognitive impairment and the TwinsUK cohort. In the VITACOG study, individuals who received a...
Source: Neurobiology of Aging - February 13, 2019 Category: Geriatrics Authors: Flitton M, Rielly N, Warman R, Warden D, Smith AD, Macdonald IA, Knight HM Tags: Neurobiol Aging Source Type: research

Corticospinal control of normal and visually guided gait in healthy older and younger adults.
Abstract We investigated age-related differences in corticospinal control of muscle activity during normal and visually guided (VG) walking. Young (n = 15, 22.1 ± 1.7 years) and older (n = 15, 68.3 ± 2.7 years) participants performed normal walking and VG walking requiring precise foot placement based on visual cues. Coherence analysis was used to quantify coupling between electroencephalography and electromyography from the anterior tibial muscle (corticomuscular) and between the 2 ends of the anterior tibial muscle (intramuscular) at 15-50 Hz during the swing phase of walki...
Source: Neurobiology of Aging - February 13, 2019 Category: Geriatrics Authors: Spedden ME, Choi JT, Nielsen JB, Geertsen SS Tags: Neurobiol Aging Source Type: research

Lentiviral vector-mediated overexpression of Klotho in the brain improves Alzheimer's disease-like pathology and cognitive deficits in mice.
Abstract Alzheimer's disease (AD) is the most common type of senile dementia. The antiaging gene Klotho is reported to decline in the brain of patients and animals with AD. However, the role of Klotho in the progression of AD remains elusive. The present study explored the effects and underlying mechanism of Klotho in a mouse model of AD. The upregulation of cerebral Klotho expression was mediated by an intracerebroventricular injection of a lentiviral vector that encoded Klotho (LV-KL) in 7-month-old amyloid precursor protein/presenilin 1 transgenic mice. Three months later, LV-KL significantly induced Klotho ove...
Source: Neurobiology of Aging - February 13, 2019 Category: Geriatrics Authors: Zeng CY, Yang TT, Zhou HJ, Zhao Y, Kuang X, Duan W, Du JR Tags: Neurobiol Aging Source Type: research

Plasma microRNA profiling distinguishes patients with frontotemporal dementia from healthy subjects.
Abstract The purpose of this study was to develop an easy and minimally invasive assay to detect a plasma miRNA profile in frontotemporal dementia (FTD) patients, with the final aim of discriminating between FTD patients and healthy controls (HCs). After a global miRNA profiling, significant downregulation of miR-663a, miR-502-3p, and miR-206 (p = 0.0001, p = 0.0002, and p = 0.02 respectively) in FTD patients was confirmed when compared with HCs in a larger case-control sample. Moreover, miR-663a and miR-502-3p showed significant differences in both genders, whereas miR-206, only in male subjects. T...
Source: Neurobiology of Aging - February 5, 2019 Category: Geriatrics Authors: Grasso M, Piscopo P, Talarico G, Ricci L, Crestini A, Tosto G, Gasparini M, Bruno G, Denti MA, Confaloni A Tags: Neurobiol Aging Source Type: research

ITPKB and ZNF184 are associated with Parkinson's disease risk in East Asians.
Abstract A recent meta-analysis of Parkinson's disease (PD) genome-wide association studies has identified 17 novel risk loci in the European population. We aim to assess if these reported novel risk loci are similarly implicated in PD risk within the East Asian population by analyzing the reported risk single nucleotide polymorphism or proxy single nucleotide polymorphism in 14,006 East Asian samples (779 patients and 13,227 controls). We found that 9 of the 17 reported novel PD risk loci showed very similar effects in Europeans and East Asians (I2 = 0 to 10.7%), of which 2 loci ITPKB and ZNF184 were signifi...
Source: Neurobiology of Aging - February 2, 2019 Category: Geriatrics Authors: Chew EGY, Tan LCS, Au WL, Prakash KM, Liu J, Foo JN, Tan EK Tags: Neurobiol Aging Source Type: research

Early and late effects of maternal experience on hippocampal neurogenesis, microglia, and the circulating cytokine milieu.
Abstract The maternal brain displays considerable plasticity, and motherhood is associated with changes in affective and cognitive function. Motherhood can alter the trajectory of brain aging, including modifications to neuroplasticity and cognition. Here, we investigated the short- and long-term effects of motherhood on hippocampal neurogenesis, microglial density and morphology, and circulating cytokines, domains known to be altered with age and implicated in cognition and mood. Female rats were bred then euthanized during gestation or at various postpartum time points, culminating in middle age, and nulliparous...
Source: Neurobiology of Aging - February 2, 2019 Category: Geriatrics Authors: Eid RS, Chaiton JA, Lieblich SE, Bodnar TS, Weinberg J, Galea LAM Tags: Neurobiol Aging Source Type: research

Age-dependent changes in clock neuron structural plasticity and excitability are associated with a decrease in circadian output behavior and sleep.
Abstract Aging has significant effects on circadian behavior across a wide variety of species, but the underlying mechanisms are poorly understood. Previous work has demonstrated the age-dependent decline in behavioral output in the model organism Drosophila. We demonstrate that this age-dependent decline in circadian output is combined with changes in daily activity of Drosophila. Aging also has a large impact on sleep behavior, significantly increasing sleep duration while reducing latency. We used electrophysiology to record from large ventral lateral neurons of the Drosophila circadian clock, finding a signifi...
Source: Neurobiology of Aging - February 2, 2019 Category: Geriatrics Authors: Curran JA, Buhl E, Tsaneva-Atanasova K, Hodge JJL Tags: Neurobiol Aging Source Type: research

Associations of amygdala volume and shape with transactive response DNA-binding protein 43 (TDP-43) pathology in a community cohort of older adults.
Abstract Transactive response DNA-binding protein 43 (TDP-43) pathology is common in old age and is strongly associated with cognitive decline and dementia above and beyond contributions from other neuropathologies. TDP-43 pathology in aging typically originates in the amygdala, a brain region also affected by other age-related neuropathologies such as Alzheimer's pathology. The purpose of this study was two-fold: to determine the independent effects of TDP-43 pathology on the volume, as well as shape, of the amygdala in a community cohort of older adults, and to determine the contribution of amygdala volume to th...
Source: Neurobiology of Aging - January 31, 2019 Category: Geriatrics Authors: Makkinejad N, Schneider JA, Yu J, Leurgans SE, Kotrotsou A, Evia AM, Bennett DA, Arfanakis K Tags: Neurobiol Aging Source Type: research

Is there a specific memory signature associated with A β-PET positivity in patients with amnestic mild cognitive impairment?
We examined whether a positive ([18F]Florbetapir) beta amyloid positron emission tomography scan, supporting underlying Alzheimer's disease pathophysiology, was associated with specific memory deficits in 48 patients with aMCI (33 beta amyloid positive, 15 beta amyloid negative). Memory was evaluated using an autobiographical fluency task and a word-list learning task with 2 different encoding types (shallow/incidental versus deep/intentional). Compared with 40 beta amyloid-negative controls, both aMCI subgroups demonstrated severe deficits in the global memory score and in most subscores of both tasks. Finer-grained analy...
Source: Neurobiology of Aging - January 31, 2019 Category: Geriatrics Authors: Tomadesso C, Gonneaud J, Egret S, Perrotin A, Pélerin A, de Flores R, de la Sayette V, Desgranges B, Chételat G, La Joie R Tags: Neurobiol Aging Source Type: research

Prenatal noise stress aggravates cognitive decline and the onset and progression of beta amyloid pathology in a mouse model of Alzheimer's disease.
Abstract Environmental distresses occurring during the sensitive periods of early life may exacerbate the vulnerability to develop physical and mental diseases in old age. Studies have shown the impact of prenatal stress (PS) on the endocrine development and reprogramming of hypothalamic-pituitary-adrenal axis functions in association with cognitive development and susceptibility to neuropsychiatric diseases. Long-term exposure to glucocorticoids can damage the brain and intensify the progression of Alzheimer's disease (AD)-like neuropathological changes, especially in females. There is, however, less information ...
Source: Neurobiology of Aging - January 30, 2019 Category: Geriatrics Authors: Jafari Z, Okuma M, Karem H, Mehla J, Kolb BE, Mohajerani MH Tags: Neurobiol Aging Source Type: research

Par3 regulates polarized convergence between APP and BACE1 in hippocampal neurons.
Abstract The convergence between amyloid precursor protein (APP) and its β-secretase β-site APP cleaving enzyme 1 (BACE1) is a prerequisite for the generation of β-amyloid peptide, a key pathogenic agent for Alzheimer's disease. Yet the underlying molecular mechanisms regulating their convergence remain unclear. Here, we show that the polarity protein partitioning-defective 3 (Par3) regulates the polarized convergence between APP and BACE1 in hippocampal neurons. Par3 forms a complex with BACE1 through its first PDZ domain, which is important for regulating BACE1 endosome-to-TGN trafficking. In the ...
Source: Neurobiology of Aging - January 30, 2019 Category: Geriatrics Authors: Sun M, Huang C, Wang H, Zhang H Tags: Neurobiol Aging Source Type: research

Acute treatment with the PDE4 inhibitor roflumilast improves verbal word memory in healthy old individuals: a double-blind placebo-controlled study.
Abstract There is ample evidence that phosphodiesterase 4 (PDE4) inhibition can improve memory performance in animal studies. In the present study, we examined the acute effects of the PDE4 inhibitor roflumilast on memory performance in healthy individuals (60-80 years of age). We tested the effects of acute roflumilast administration (100, 250, 1000 μg) in a double-blind, placebo-controlled, 4-way crossover design. Participants were first screened for their verbal word memory performance to ensure normal memory performance (within 0.5 standard deviation from norm score; n = 20) Drug effects on m...
Source: Neurobiology of Aging - January 26, 2019 Category: Geriatrics Authors: Blokland A, Van Duinen MA, Sambeth A, Heckman PRA, Tsai M, Lahu G, Uz T, Prickaerts J Tags: Neurobiol Aging Source Type: research

Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults.
Cognitive aging is not created equally: differentiating unique cognitive phenotypes in "normal" adults. Neurobiol Aging. 2019 Jan 24;77:13-19 Authors: Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH Abstract Age-related cognitive decline is a public health problem but highly diverse and difficult to predict. We captured nonoverlapping cognitive phenotypes in high-functioning adults and identified baseline factors differentiating trajectories. Three hundred fourteen functionally normal adults (M = 69 y) completed 2+ visits. Pa...
Source: Neurobiology of Aging - January 24, 2019 Category: Geriatrics Authors: Casaletto KB, Elahi FM, Staffaroni AM, Walters S, Contreras WR, Wolf A, Dubal D, Miller B, Yaffe K, Kramer JH Tags: Neurobiol Aging Source Type: research

Event-related potentials associated with auditory attention capture in younger and older adults.
Abstract A deviant-related negativity (DRN), mismatch negativity (MMN), and P3a are electrophysiological measures thought to reflect processes involved in the involuntary switching of attention to a task-irrelevant stimulus. The purpose of this article was to determine whether healthy older adults involuntarily detect unattended auditory stimuli as efficiently as younger adults. To test this, 20 younger adults (aged 18-30 years) and 20 older adults (aged 65+ years) were presented with to-be-ignored auditory sequences consisting of frequently presented 80 dB SPL standards and rarely presented increments (+10&n...
Source: Neurobiology of Aging - January 24, 2019 Category: Geriatrics Authors: Morrison C, Kamal F, Campbell K, Taler V Tags: Neurobiol Aging Source Type: research

Prestimulus and poststimulus oscillatory activity predicts successful episodic encoding for both young and older adults.
Abstract Healthy aging is associated with declines in episodic memory performance that are due in part to deficits in encoding. Emerging results from young adult studies suggest that the neural activity during the time preceding stimulus presentation is sensitive to episodic memory performance. It is unknown whether age-related declines in episodic memory are due solely to changes in the recruitment of processes elicited by stimuli during encoding or also in processes recruited in anticipation of these stimuli. Here, we recorded oscillatory electroencephalography while young and old participants encoded visual and...
Source: Neurobiology of Aging - January 21, 2019 Category: Geriatrics Authors: Strunk J, Duarte A Tags: Neurobiol Aging Source Type: research

Multimodal MRI evaluation of parkinsonian limbic pathologies.
Abstract Previous multimodal magnetic resonance imaging (MRI) studies of parkinsonian syndromes have focused primarily on motor-related basal ganglia structures. The present study investigated MRI changes in nonmotor-related limbic structures in 35 Parkinson's disease, 16 multiple system atrophy parkinsonian subtype, 17 progressive supranuclear palsy, and 37 control subjects. Mean diffusivity (MD), fractional anisotropy, transverse relaxation rate (R2*), quantitative susceptibility mapping, and volume measurements were obtained from the amygdala, hippocampus, and nucleus accumbens (NAc) to examine differences betw...
Source: Neurobiology of Aging - January 16, 2019 Category: Geriatrics Authors: Wang EW, Du G, Lewis MM, Lee EY, De Jesus S, Kanekar S, Kong L, Huang X Tags: Neurobiol Aging Source Type: research

Increased cerebral blood volume in small arterial vessels is a  correlate of amyloid-β-related cognitive decline.
This study was aimed at investigating long-term effects of Aβ burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aβ burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years]. After 2 years, inflow-based vascular space occupancy at ultra-high field strength of 7-Tesla was administered for measuring CBVa, and neuropsychological testing for cognitive decline. Crushing gradients were incorporated during MR-imaging to suppress signal...
Source: Neurobiology of Aging - January 10, 2019 Category: Geriatrics Authors: Hua J, Lee S, Blair NIS, Wyss M, van Bergen JMG, Schreiner SJ, Kagerer SM, Leh SE, Gietl AF, Treyer V, Buck A, Nitsch RM, Pruessmann KP, Lu H, Van Zijl PCM, Albert M, Hock C, Unschuld PG Tags: Neurobiol Aging Source Type: research

Aged rats with preserved memory dynamically recruit hippocampal inhibition in a local/global cue mismatch environment.
Abstract Similar to elderly humans, aged outbred Long-Evans rats exhibit individual differences in memory abilities, including a subset of aged rats that maintain memory function on par with young adults. Such individuals provide a basis for investigating mechanisms of resilience to age-related decline. The present study examined hippocampal gene expression in young adults and aged rats with preserved memory function under behavioral task conditions well established for assessing information processing central to the formation of episodic memory. Although behavioral measures and hippocampal gene induction associat...
Source: Neurobiology of Aging - January 8, 2019 Category: Geriatrics Authors: Branch A, Monasterio A, Blair G, Knierim JJ, Gallagher M, Haberman RP Tags: Neurobiol Aging Source Type: research

Expression of neurogenic markers in Alzheimer's disease: a systematic review and metatranscriptional analysis.
We present findings from 11 postmortem studies that were identified by a systematic search within the literature, focusing on what markers of neurogenesis were used, which stages of AD were investigated, and whether the studies had any confounding information that could potentially hinder clear interpretation of the presented data. In addition, we also review studies that examined transcriptomic changes in human AD postmortem brains and reveal upregulated expression of neural progenitor and proliferation markers and downregulated expression of later neurogenic markers in AD. Taken together, the existing literature seems to...
Source: Neurobiology of Aging - January 8, 2019 Category: Geriatrics Authors: Gatt A, Lee H, Williams G, Thuret S, Ballard C Tags: Neurobiol Aging Source Type: research

External cueing facilitates auditory-motor integration for speech control in individuals with Parkinson's disease.
Abstract Instructing individuals with Parkinson's disease (PD) to speak loudly and clearly with external cues leads to improvements of their speech in loudness, pitch, and articulatory movement, but the underlying neural mechanisms are largely unknown. The present event-related potential study investigated whether and how external cueing can facilitate auditory-motor control of speech production in PD. Individuals with PD and healthy controls produced sustained vowels with internal and external auditory cues while hearing their voice pitch-shifted -200 cents. Individuals with PD produced significantly larger vocal...
Source: Neurobiology of Aging - January 8, 2019 Category: Geriatrics Authors: Huang X, Fan H, Li J, Jones JA, Wang EQ, Chen L, Chen X, Liu H Tags: Neurobiol Aging Source Type: research

Age-related cortical signatures of human sleep electroencephalography.
ier J Abstract Accumulating evidence demonstrates a direct relationship between impaired neural integrity and disrupted sleep physiology in normal and pathological aging. However, previous work has focus almost exclusively on nonrapid eye movement sleep electroencephalography as a proxy of cortical integrity with aging. Whether this relationship holds true for rapid eye movement sleep electroencephalography is unknown. Our results show that age-related reduction in low-frequency delta activity during both rapid eye movement and nonrapid eye movement sleep was statistically mediated by the thinning of the medial fr...
Source: Neurobiology of Aging - January 6, 2019 Category: Geriatrics Authors: Latreille V, Gaubert M, Dubé J, Lina JM, Gagnon JF, Carrier J Tags: Neurobiol Aging Source Type: research

Spatial updating deficits in human aging are associated with traces of former memory representations.
Abstract The ability to update spatial memories is important for everyday situations, such as remembering where we left our keys or parked our car. Although rodent studies have suggested that old age might impair spatial updating, direct evidence for such a deficit in humans is missing. Here, we tested whether spatial updating deficits occur in human aging, whether the learning mode influences spatial updating, and what mnemonic mechanism underlies the presumed deficits. To address these questions, younger and older participants had to indicate the latest location of relocated items, following either incidental or...
Source: Neurobiology of Aging - January 2, 2019 Category: Geriatrics Authors: Merhav M, Riemer M, Wolbers T Tags: Neurobiol Aging Source Type: research

The association between repeat number in C9orf72 and phenotypic variability in Turkish patients with frontotemporal lobar degeneration.
Abstract Frontotemporal lobar degeneration (FTLD) describes a group of progressive brain disorders. The expansion of a noncoding GGGGCC (G4C2) hexanucleotide repeat in the C9orf72 gene is a major cause of both familial FTLD and amyotrophic lateral sclerosis. The aim of this study was to determine the prevalence of C9orf72 G4C2-repeat expansion in a Turkish population with FTLD and to determine its effects on the phenotype. The G4C2 expansion in the C9orf72 gene was analyzed in 100 cases of FTLD without mutations of the MAPT, PGRN, CHMP2B, VCP, TARDBP, and FUS genes and 100 age-matched healthy controls by using rep...
Source: Neurobiology of Aging - December 28, 2018 Category: Geriatrics Authors: Erzurumluoglu E, Cilingir O, Ozbabalik Adapinar BD, Bilgic B, Kocagil S, Ozen H, Durak Aras B, Yenilmez C, Artan S Tags: Neurobiol Aging Source Type: research

Diet and biomarkers of Alzheimer's disease: a systematic review and meta-analysis.
Abstract Alzheimer's disease (AD) risk increases with age and lacks efficacious pharmacological options. Summaries of the existing evidence reveal an association between Mediterranean-style diet adherence and reduced AD incidence; however, no review has investigated this relationship with respect to the hallmark AD biomarkers (tau and beta-amyloid) that manifest decades before clinical symptomatology. MEDLINE, PubMed, PsycINFO, Google Scholar, and SCOPUS databases were systematically searched to identify peer-reviewed articles investigating diet and AD biomarkers in the last 2 decades. Two thousand seven hundred t...
Source: Neurobiology of Aging - December 27, 2018 Category: Geriatrics Authors: Hill E, Goodwill MA, Gorelik A, Szoeke C Tags: Neurobiol Aging Source Type: research

DNA methylation variability in Alzheimer's disease.
Abstract DNA methylation plays a critical role in brain aging and Alzheimer's disease (AD). While prior studies have largely focused on testing mean DNA methylation, DNA methylation instability (quantified by DNA methylation variability) may also affect disease susceptibility. Using DNA methylation data collected by the Religious Orders Study and the Rush Memory and Aging Project, we identified 249 and 115 variably methylated probes (VMPs) associated with amyloid-β and neurofibrillary tangles, respectively. These VMPs clustered into 133 and 14 regions, respectively. Notably, we found that most of these VMPs d...
Source: Neurobiology of Aging - December 21, 2018 Category: Geriatrics Authors: Huo Z, Zhu Y, Yu L, Yang J, De Jager P, Bennett DA, Zhao J Tags: Neurobiol Aging Source Type: research

Screening of a neuronal cell model of tau pathology for therapeutic compounds.
w E Abstract We have developed a cell-based phenotypic automated high-content screening approach for N2a cells expressing the pro-aggregant repeat domain of tau protein (tauRDΔK), which allows analysis of a chemogenomic library of 1649 compounds for their effect on the inhibition or stimulation of intracellular tau aggregation. We identified several inhibitors and stimulators of aggregation and achieved a screening reproducibility>85% for all data. We identified 18 potential inhibitors (= 1.1% of the library) and 10 stimulators (= 0.6% of the library) of tau aggregation in this cell model of tau pathology...
Source: Neurobiology of Aging - December 13, 2018 Category: Geriatrics Authors: Pickhardt M, Tassoni M, Denner P, Kurkowsky B, Kitanovic A, Möhl C, Fava E, Mandelkow E Tags: Neurobiol Aging Source Type: research

Neuroimaging findings and clinical trajectories of Lewy body disease in patients with MCI.
We present an intriguing group of 13 patients with MCI preceding (2.9 ± 1.9 years) parkinsonism (MCI-P), and eventually dementia 4.6 ± 1.6 years later (6 patients), whereas 7 patients remained dementia free after 4.7 ± 2.7 years. Neuropsychological tests, dopamine transporter (DAT) single photon emission computed tomography, and 18F-fluorodeoxyglucose positron emission tomography were compared with healthy controls and with cognitively normal patients with Parkinson's disease (PD-MOT). Compared to controls, MCI-P but not PD-MOT showed significant posterior temporo-parieto-occipital hypom...
Source: Neurobiology of Aging - December 13, 2018 Category: Geriatrics Authors: Massa F, Arnaldi D, De Cesari F, Girtler N, Brugnolo A, Grazzini M, Bauckneht M, Meli R, Morbelli S, Pardini M, Sambuceti G, De Carli F, Tiraboschi P, Nobili F Tags: Neurobiol Aging Source Type: research

Uric acid enhances longevity and endurance and protects the brain against ischemia.
Abstract Among mammals, there is a positive correlation between serum uric acid (UA) levels and life span. Humans have high levels of UA because they lack a functional urate oxidase (UOX) enzyme that is present in shorter lived mammals. Here, we show that male and female mice with UOX haploinsufficiency exhibit an age-related elevation of UA levels, and that the life span of female but not male UOX+/- mice is significantly increased compared to wild-type mice. Serum UA levels are elevated in response to treadmill exercise in UOX+/- mice, but not wild-type mice, and the endurance of the UOX+/- mice is significantly...
Source: Neurobiology of Aging - December 12, 2018 Category: Geriatrics Authors: Cutler RG, Camandola S, Feldman NH, Yoon JS, Haran JB, Arguelles S, Mattson MP Tags: Neurobiol Aging Source Type: research

Impairment in complex activities of daily living is related to neurodegeneration in Alzheimer's disease-specific regions.
Abstract Impairment in instrumental activities of daily living (IADL) is an early clinical feature of Alzheimer's disease (AD). The neurobiology underlying IADL disruptions is still unclear. We aimed to investigate the relationship between IADL functioning and cortical atrophy across the AD spectrum. We selected 162 memory-clinic subjects with subjective cognitive decline (n = 49), mild cognitive impairment (n = 26) or AD dementia (n = 87), and an available structural MRI acquired at 3.0 Tesla and Amsterdam IADL Questionnaire (A-IADL-Q) assessment. We used linear regression correcting for age, ...
Source: Neurobiology of Aging - November 26, 2018 Category: Geriatrics Authors: Jutten RJ, Dicks E, Vermaat L, Barkhof F, Scheltens P, Tijms BM, Sikkes SAM Tags: Neurobiol Aging Source Type: research

Social housing protects against age-related working memory decline independently of physical enrichment in rats.
In this study, rats were socially housed or nonsocially housed throughout their lifespan and tested in the radial arm maze to measure working memory (WM) and reference memory longitudinally at 3 ages. In old age, exclusively, socially housed rats made significantly less WM errors than nonsocially housed rats, while reference memory errors did not differ between groups at any age. Anxiety, as assessed behaviorally and physiologically, could not account for the observed differences in WM. These data provide the first evidence that social enrichment alone can prevent age-related WM deficits in spite of the effects of practice...
Source: Neurobiology of Aging - November 23, 2018 Category: Geriatrics Authors: Templer VL, Wise TB, Heimer-McGinn VR Tags: Neurobiol Aging Source Type: research

Iron-related nigral degeneration influences functional topology mediated by striatal dysfunction in Parkinson's disease.
In conclusion, our findings reveal that iron-related nigral degeneration possibly influences the functional topology mediated by striatal dysfunction, which extends the scientific understanding of PD pathogenesis. PMID: 30554085 [PubMed - as supplied by publisher] (Source: Neurobiology of Aging)
Source: Neurobiology of Aging - November 22, 2018 Category: Geriatrics Authors: Guan X, Zhang Y, Wei H, Guo T, Zeng Q, Zhou C, Wang J, Gao T, Xuan M, Gu Q, Xu X, Huang P, Pu J, Zhang B, Liu C, Zhang M Tags: Neurobiol Aging Source Type: research

Association between telomere length and cognitive ability in a community-based sample.
Abstract Prior research suggests that telomere length is a biomarker of cognitive aging; however, literature has demonstrated conflicting findings to date. The present study uses data from the Dallas Heart Study, N = 2606, to assess the association between telomere length and cognitive ability on the Montreal Cognitive Assessment. The data do not support a relationship between telomere length and general cognitive functioning, (β = 0.016, SE = 0.31, p = 0.407). The data further replicate the negative findings within current literature. PMID: 30544048 [PubMed - as supplied by publisher...
Source: Neurobiology of Aging - November 20, 2018 Category: Geriatrics Authors: Kaja R, Reyes SM, Rossetti HC, Brown ES Tags: Neurobiol Aging Source Type: research

Presence of tau astrogliopathy in frontotemporal dementia caused by a novel Grn nonsense (Trp2*) mutation.
We present a family with autosomal dominant frontotemporal lobar degeneration caused by a novel GRN nonsense mutation (c.5G>A: p.Trp2*) in which the proband's brain also showed prominent glial tauopathy consistent with an aging-related tau astrogliopathy. Astrocytic tauopathy, 4R(+) and 3R(-) immunoreactive, was characterized by thorn-shaped astrocytes present in subpial, subependymal, and perivascular areas, and in gray matter; plus granular or fuzzy tau immunoreactivity in astrocytic processes in gray matter, either solitary or clustered in different regions. Some neurofibrillary tangles and pretangles, both 3R and 4R...
Source: Neurobiology of Aging - November 20, 2018 Category: Geriatrics Authors: Gómez-Tortosa E, Baradaran-Heravi Y, González Alvarez V, Sainz MJ, Prieto-Jurczynska C, Guerrero-López R, Agüero Rabes P, Van Broeckhoven C, van der Zee J, Rábano Gutiérrez A, EU EOD Consortium Tags: Neurobiol Aging Source Type: research

Striking reduction in neurons and glial cells in anterior thalamic nuclei of older patients with Down syndrome.
Abstract The anterior thalamic nuclei are important for spatial and episodic memory, however, surprisingly little is known about the status of these nuclei in neurological conditions that present with memory impairments, such as Down syndrome. We quantified neurons and glial cells in the anterior thalamic nuclei of four older patients with Down syndrome. There was a striking reduction in the volume of the anterior thalamic nuclei and this appeared to reflect the loss of approximately 70% of neurons. The number of glial cells was also reduced but to a lesser degree than neurons. The anterior thalamic nuclei appear ...
Source: Neurobiology of Aging - November 17, 2018 Category: Geriatrics Authors: Perry JC, Pakkenberg B, Vann SD Tags: Neurobiol Aging Source Type: research

Genetic analysis of neurodegenerative diseases in a pathology cohort.
oncoso JC, Scholz SW Abstract Molecular genetic research provides unprecedented opportunities to examine genotype-phenotype correlations underlying complex syndromes. To investigate pathogenic mutations and genotype-phenotype relationships in diverse neurodegenerative conditions, we performed a rare variant analysis of damaging mutations in autopsy-confirmed neurodegenerative cases from the Johns Hopkins Brain Resource Center (n = 1243 patients). We used NeuroChip genotyping and C9orf72 hexanucleotide repeat analysis to rapidly screen our cohort for disease-causing mutations. In total, we identified 42 indivi...
Source: Neurobiology of Aging - November 17, 2018 Category: Geriatrics Authors: Blauwendraat C, Pletnikova O, Geiger JT, Murphy NA, Abramzon Y, Rudow G, Mamais A, Sabir MS, Crain B, Ahmed S, Rosenthal LS, Bakker CC, Faghri F, Chia R, Ding J, Dawson TM, Pantelyat A, Albert MS, Nalls MA, Resnick SM, Ferrucci L, Cookson MR, Hillis AE, T Tags: Neurobiol Aging Source Type: research

Administration of the benzodiazepine midazolam increases tau phosphorylation in the mouse brain.
nel E Abstract Preclinical studies have shown that anesthesia might accelerate the clinical progression of Alzheimer's disease (AD) and can have an impact on tau pathology, a hallmark of AD. Although benzodiazepines have been suggested to increase the risk of incident dementia, their impact on tau pathology in vivo is unknown. We thus examined the impact of midazolam, a benzodiazepine that is often administered perioperatively as an anxiolytic, on tau hyperphosphorylation in nontransgenic and in hTau mice, the latter a model of AD-like tau pathology. The acute administration of midazolam in C57BL/6 mice was a...
Source: Neurobiology of Aging - November 8, 2018 Category: Geriatrics Authors: Whittington RA, Virág L, Gratuze M, Lewkowitz-Shpuntoff H, Cheheltanan M, Petry F, Poitras I, Morin F, Planel E Tags: Neurobiol Aging Source Type: research

Genetic variants of PARK genes in Korean patients with early-onset Parkinson's disease.
Abstract Early-onset Parkinson's disease (EOPD) can be linked to different genetic backgrounds depending on the disease characteristics. In Korean patients with EOPD, however, only 5 PARK genes have been tested. We recruited 70 patients with EOPD from 4 hospitals in Korea, and 12 PARK genes were screened via multigene panel sequencing. Large insertions or deletions were confirmed by multiplex ligation-dependent probe amplification. We found 20 rare variants (2 in SNCA, 2 in PRKN, 6 in LRRK2, 3 in PINK1, 1 in DJ1, 4 in FBX07, 1 in HTRA2, and 1 in EIG4G1) in 20 subjects regardless of heterogeneity. Two pathogenic va...
Source: Neurobiology of Aging - November 7, 2018 Category: Geriatrics Authors: Youn J, Lee C, Oh E, Park J, Kim JS, Kim HT, Cho JW, Park WY, Jang W, Ki CS Tags: Neurobiol Aging Source Type: research

Age-dependent behavioral and biochemical characterization of single APP knock-in mouse (APPNL-G-F/NL-G-F) model of Alzheimer's disease.
Abstract Saito et al developed a novel amyloid precursor protein (APP) knock-in mouse model (APPNL-G-F) for Alzheimer's disease (AD) to overcome the problem of overexpression of APP in available transgenic mouse models. However, this new mouse model for AD is not fully characterized age-dependently with respect to behavioral and biochemical changes. Therefore, in the present study, we performed an age-dependent behavioral and biochemical characterization of this newly developed mouse model. Here, we used 3-, 6-, 9-, and 12-month-old APPNL-G-F and C57BL/6J mice. We used a separate cohort of animals at each age...
Source: Neurobiology of Aging - November 5, 2018 Category: Geriatrics Authors: Mehla J, Lacoursiere SG, Lapointe V, McNaughton BL, Sutherland RJ, McDonald RJ, Mohajerani MH Tags: Neurobiol Aging Source Type: research