Abstract:
IMPORTANCE:Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE:To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS:Longitudinal study of consecutive patients who underwent 2 lumbar punctures between the beginning of 1995 and the end of 2010 within the memory clinic-based Amsterdam Dementia Cohort. The study included 163 patients: 37 cognitively normal participants (mean [SE] age, 64 [2] years; 38% female; and mean [SE] Mini-Mental State Examination [MMSE] score, 28 [0.3]), 61 patients with mild cognitive impairment (MCI) (mean [SE] age, 68 [1] years; 38% female; and mean [SE] MMSE score, 27 [0.3]), and 65 patients with AD (mean [SE] age, 65 [1] years; 45% female; and mean [SE] MMSE score, 22 [0.7]). The mean (SE) interval between lumbar punctures was 2.0 (0.1) years, and the mean (SE) duration of cognitive follow-up was 3.8 (0.2) years. Measurements of CSF NGRN levels were obtained in January and February 2014. MAIN OUTCOME AND MEASURE:Levels of NGRN in CSF samples. RESULTS:Baseline CSF levels of NGRN in patients with AD (median level, 2381 pg/mL [interquartile range, 1651-3416 pg/mL]) were higher than in cognitively normal participants (median level, 1712 pg/mL [interquartile range, 1206-2724 pg/mL]) (P = .04). Baseline NGRN levels were highly correlated with total tau and tau phosphorylated at threonine 181 in all patient groups (all P < .001), but not with Aβ42. Baseline CSF levels of NGRN were also higher in patients with MCI who progressed to AD (median level, 2842 pg/mL [interquartile range, 1882-3950 pg/mL]) compared with those with stable MCI (median level, 1752 pg/mL [interquartile range, 1024-2438 pg/mL]) (P = .004), and they were predictive of progression from MCI to AD (hazard ratio, 1.8 [95% CI, 1.1-2.9]; stratified by tertiles). Linear mixed-model analyses demonstrated that within-person levels of NGRN increased over time in cognitively normal participants (mean [SE] level, 90 [45] pg/mL per year; P < .05) but not in patients with MCI or AD. CONCLUSIONS AND RELEVANCE:Neurogranin is a promising biomarker for AD because levels were elevated in patients with AD compared with cognitively normal participants and predicted progression from MCI to AD. Within-person levels of NGRN increased in cognitively normal participants but not in patients with later stage MCI or AD, which suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss.
journal_name
JAMA Neuroljournal_title
JAMA neurologyauthors
Kester MI,Teunissen CE,Crimmins DL,Herries EM,Ladenson JH,Scheltens P,van der Flier WM,Morris JC,Holtzman DM,Fagan AMdoi
10.1001/jamaneurol.2015.1867subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1275-80issue
11eissn
2168-6149issn
2168-6157pii
2436595journal_volume
72pub_type
杂志文章相关文献
JAMA Neurology文献大全abstract:IMPORTANCE:Mild strokes have been poorly represented in thrombolytic trials and only a few series have reported outcomes after treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA) after mild stroke. OBJECTIVE:To report treatment complications and short-term outcomes in patients with mild str...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.4354
更新日期:2015-04-01 00:00:00
abstract:IMPORTANCE:Intravenous recombinant tissue plasminogen activator (alteplase) was approved by the US Food and Drug Administration in 1996 for the treatment of acute ischemic stroke. Nearly 20 years later, it remains the only approved treatment, despite limitations in both efficacy and safety. With a growing capacity for ...
journal_title:JAMA neurology
pub_type: 杂志文章,评审
doi:10.1001/jamaneurol.2015.0835
更新日期:2015-08-01 00:00:00
abstract:IMPORTANCE:The extent to which large-caliber axonal degeneration contributes to Alzheimer disease (AD) progression is unknown. Cerebrospinal fluid (CSF) neurofilament light (NFL) concentration is a general marker of damage to large-caliber myelinated axons. OBJECTIVE:To test whether CSF NFL concentration is associated...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2015.3037
更新日期:2016-01-01 00:00:00
abstract:Importance:Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. Objective:To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. Design, Setting, and Participants:The prospective International Deep Br...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2017.4317
更新日期:2018-03-01 00:00:00
abstract:Importance:Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been co...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.1534
更新日期:2019-06-17 00:00:00
abstract:Importance:The pathophysiologic mechanisms of Guillain-Barré syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. Objective:To identify specific clinical features of GBS associated with ZIKV infection. Design, Setting, and Participants:During the ZIKV epidem...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2018.1058
更新日期:2018-09-01 00:00:00
abstract:IMPORTANCE:Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality. OBJECTIVE:To identify the underlying molecular cause ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.0363
更新日期:2016-07-01 00:00:00
abstract:IMPORTANCE:The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders. OBJECTIVE:To investigate a large family with late-onset AD (LOAD)...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2015.0979
更新日期:2015-08-01 00:00:00
abstract:Importance:A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disor...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.5131
更新日期:2017-05-01 00:00:00
abstract:Importance:Functional neurological disorders (FND) are common sources of disability in medicine. Patients have often been misdiagnosed, correctly diagnosed after lengthy delays, and/or subjected to poorly delivered diagnoses that prevent diagnostic understanding and lead to inappropriate treatments, iatrogenic harm, un...
journal_title:JAMA neurology
pub_type: 杂志文章,评审
doi:10.1001/jamaneurol.2018.1264
更新日期:2018-09-01 00:00:00
abstract::IMPORTANCE The search for novel Alzheimer disease (AD) genes or pathologic mutations within known AD loci is ongoing. The development of array technologies has helped to identify rare recessive mutations among long runs of homozygosity (ROHs), in which both parental alleles are identical. Caribbean Hispanics are known...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.3545
更新日期:2013-10-01 00:00:00
abstract:Importance:Cognitive impairment in multiple sclerosis (MS) can lead to reduced quality of life, social functioning, and employment. Few studies have investigated cognitive outcomes among patients with pediatric-onset MS (POMS) over the long term. Objective:To compare long-term information-processing efficiency between...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.1546
更新日期:2019-06-17 00:00:00
abstract:Importance:As the life expectancy of people with Down syndrome (DS) has markedly increased over the past decades, older adults with DS may be experiencing a higher incidence of aging conditions. In addition to longevity, the amyloid precursor protein gene located on chromosome 21 places individuals with DS at a high ri...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2018.2210
更新日期:2018-11-01 00:00:00
abstract:Importance:Interictal epileptiform discharges (IEDs) in electroencephalograms (EEGs) are a biomarker of epilepsy, seizure risk, and clinical decline. However, there is a scarcity of experts qualified to interpret EEG results. Prior attempts to automate IED detection have been limited by small samples and have not demon...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.3485
更新日期:2020-01-01 00:00:00
abstract:IMPORTANCE:Markedly enlarged Virchow-Robin spaces throughout the striatum appear occasionally on magnetic resonance imaging (MRI) scans of the elderly, and this type of striatum is known as the Swiss cheese striatum (SCS); however, its clinical impact is unknown. OBJECTIVE:To determine the clinical features associated...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.286
更新日期:2014-06-01 00:00:00
abstract:Importance:This study reports the long-term epidemiologic trends of amyotrophic lateral sclerosis (ALS) based on a prospective register. Objective:To examine the 20-year epidemiologic trends of ALS in the Piemonte and Valle d'Aosta regions of Italy. Design, Setting, and Participants:The Piemonte and Valle d'Aosta Reg...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2017.1387
更新日期:2017-09-01 00:00:00
abstract:IMPORTANCE:Documentation of muscle pathology compatible with targeting of sarcolemmal aquaporin-4 (AQP4) by complement-activating IgG implies involvement of organs beyond the central nervous system in neuromyelitis optica spectrum disorders. OBSERVATIONS:We report on a 51-year-old woman who had relapsing optic neuriti...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.775
更新日期:2014-08-01 00:00:00
abstract:IMPORTANCE:Apolipoprotein E (APOE) ε4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects. OBJECTIVE:Using APOE ε4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older a...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.3978
更新日期:2015-03-01 00:00:00
abstract:Importance:Recognizing the characteristics of myelin oligodendrocyte glycoprotein autoantibody (MOG-IgG) myelitis is essential for early accurate diagnosis and treatment. Objective:To evaluate the clinical, radiologic, and prognostic features of MOG-IgG myelitis and compare with myelitis with aquaporin-4-IgG (AQP4-IgG...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2018.4053
更新日期:2019-03-01 00:00:00
abstract:Importance:Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin re...
journal_title:JAMA neurology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1001/jamaneurol.2018.2030
更新日期:2018-11-01 00:00:00
abstract:IMPORTANCE:Whether cognition is influenced by arterial stiffness in the absence of vascular disease remains uncertain. OBJECTIVE:To test the hypotheses that indirect measures of arterial stiffness are important predictors of cognitive performance and that this relationship varies depending on the presence of vascular ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2014.3873
更新日期:2015-03-01 00:00:00
abstract:IMPORTANCE:Metabolic syndrome (MetS) is thought to influence several autoimmune diseases, including multiple sclerosis (MS). Anti-inflammatory effects of treatments used for MetS, such as metformin hydrochloride and pioglitazone hydrochloride, have been demonstrated, although clinical evidence supporting use of these t...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2015.4807
更新日期:2016-05-01 00:00:00
abstract:Importance:Deposition of the pathological α-synuclein (αSynP) in the brain is the hallmark of synucleinopathies, including Parkinson disease (PD), Lewy body dementia (LBD), and multiple system atrophy (MSA). Whether real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) assays...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2020.3311
更新日期:2020-09-28 00:00:00
abstract:Importance:Apolipoprotein E ε4 (APOEε4) is the single most important genetic risk factor for Alzheimer disease. While APOEε4 is associated with increased amyloid-β burden, its association with cerebral tau pathology has been controversial. Objective:To determine whether APOEε4 is associated with medial temporal tau pa...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2019.4421
更新日期:2020-04-01 00:00:00
abstract:IMPORTANCE:Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. OBJECTIVE:To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a l...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.0086
更新日期:2016-05-01 00:00:00
abstract:Importance:Atabecestat, a nonselective oral β-secretase inhibitor, was evaluated in the EARLY trial for slowing cognitive decline in participants with preclinical Alzheimer disease. Preliminary analyses suggested dose-related cognitive worsening and neuropsychiatric adverse events (AEs). Objective:To report efficacy, ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2020.4857
更新日期:2021-01-19 00:00:00
abstract::A young man with normal neurodevelopment presented with 3 years of medically refractory, progressive epilepsy and myoclonus. Initial examination included neuroimaging, electroencephalography, and biochemical analyses, all of which were unremarkable except for mildly enlarged ventricles. Over the following year, the pa...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2016.3195
更新日期:2017-06-01 00:00:00
abstract:Importance:Advances in treatment of traumatic brain injury are hindered by the inability to monitor pathological mechanisms in individual patients for targeted neuroprotective treatment. Spreading depolarizations, a mechanism of lesion development in animal models, are a novel candidate for clinical monitoring in patie...
journal_title:JAMA neurology
pub_type: 杂志文章,多中心研究
doi:10.1001/jamaneurol.2019.4476
更新日期:2020-04-01 00:00:00
abstract:Importance:Although endovascular thrombectomy (EVT) in acute ischemic stroke is recommended by guidelines to improve functional recovery, thus far there are insufficient data on its association with mortality. Objective:To identify guideline-relevant trials of EVT vs medical therapy reporting 90-day mortality and perf...
journal_title:JAMA neurology
pub_type: 杂志文章,meta分析
doi:10.1001/jamaneurol.2019.0525
更新日期:2019-07-01 00:00:00
abstract:IMPORTANCE:Magnetic resonance imaging markers of incipient cognitive decline among healthy elderly individuals have become important for both clarifying the biological underpinnings of dementia and clinically identifying healthy individuals at high risk of cognitive decline. Even though the role of hippocampal atrophy ...
journal_title:JAMA neurology
pub_type: 杂志文章
doi:10.1001/jamaneurol.2013.3263
更新日期:2013-11-01 00:00:00