Neurogranin as a predictor of memory and executive function decline in MCI patients

Headley, Alison J.; León-Benedetti, Andrés De; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B.; Sun, Xiaoyan

doi:10.1212/wnl.0000000000005057

Cited by 48 publications

(40 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One possibility is that changes in cognitive composites may be more difficult to detect but are less confounded by measurement errors and are therefore more robust when detected. In longitudinal studies, NG has been observed to predict conversion from MCI to frank AD dementia, raising the possibility that increased NG is a robust predictor of cognitive decline only later in the disease course [34] , [35] . In partial support of this hypothesis, NG has also been associated with longitudinal cognitive decline, but only in amyloid-positive individuals [8] .…”

Section: Discussionmentioning

confidence: 99%

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Vogt

Norton

Jonaitis

et al. 2019

A&D Transl Res & Clin Interv

Self Cite

View full text Add to dashboard Cite

Introduction Neurodegeneration appears to be the biological mechanism most proximate to cognitive decline in Alzheimer's disease. We test whether t-tau and alternative biomarkers of neurodegeneration—neurogranin and neurofilament light protein (NFL)—add value in predicting subclinical cognitive decline. Methods One hundred fifty cognitively unimpaired participants received a lumbar puncture for cerebrospinal fluid and at least two neuropsychological examinations (mean age at first visit = 59.3 ± 6.3 years; 67% female). Linear mixed effects models were used with cognitive composite scores as outcomes. Neurodegeneration interactions terms were the primary predictors of interest: age × NFL or age × neurogranin or age × t-tau. Models were compared using likelihood ratio tests. Results Age × NFL accounted for a significant amount of variation in longitudinal change on preclinical Alzheimer's cognitive composite scores, memory composite scores, and learning scores, whereas age × neurogranin and age × t-tau did not. Discussion These data suggest that NFL may be more sensitive to subclinical cognitive decline compared to other proposed biomarkers for neurodegeneration.

show abstract

Section: Discussionmentioning

confidence: 99%

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Vogt

Norton

Jonaitis

et al. 2019

A&D Transl Res & Clin Interv

Self Cite

View full text Add to dashboard Cite

show abstract

“…Postmortem studies have shown that the full-length Ng is reduced in the parietal and temporal cortex in AD patients and processed into smaller peptides measurable in CSF reflecting synaptic degeneration [24]. CSF Ng levels are elevated in both AD and mild cognitive impairment (MCI) compared to healthy controls and associated with lower cognitive function and deterioration of white matter tracts and predict cognitive decline as well as conversion from MCI to AD [25][26][27][28][29][30][31][32][33][34][35][36]. No other published study has to our knowledge investigated the association between Ng and NPS.…”

Section: Introductionmentioning

confidence: 99%

Are neuropsychiatric symptoms in dementia linked to CSF biomarkers of synaptic and axonal degeneration?

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background The underlying disease mechanism of neuropsychiatric symptoms (NPS) in dementia remains unclear. Cerebrospinal fluid (CSF) biomarkers for synaptic and axonal degeneration may provide novel neuropathological information for their occurrence. The aim was to investigate the relationship between NPS and CSF biomarkers for synaptic (neurogranin [Ng], growth-associated protein 43 [GAP-43]) and axonal (neurofilament light [NFL]) injury in patients with dementia. Methods A total of 151 patients (mean age ± SD, 73.5 ± 11.0, females n = 92 [61%]) were included, of which 64 had Alzheimer’s disease (AD) (34 with high NPS, i.e., Neuropsychiatric Inventory (NPI) score > 10 and 30 with low levels of NPS) and 18 were diagnosed with vascular dementia (VaD), 27 with mixed dementia (MIX), 12 with mild cognitive impairment (MCI), and 30 with subjective cognitive impairment (SCI). NPS were primarily assessed using the NPI. CSF samples were analyzed using enzyme-linked immunosorbent assays (ELISAs) for T-tau, P-tau, Aβ1–42, Ng, NFL, and GAP-43. Results No significant differences were seen in the CSF levels of Ng, GAP-43, and NFL between AD patients with high vs low levels of NPS (but almost significantly decreased for Ng in AD patients < 70 years with high NPS, p = 0.06). No significant associations between NPS and CSF biomarkers were seen in AD patients. In VaD (n = 17), negative correlations were found between GAP-43, Ng, NFL, and NPS. Conclusion Our results could suggest that low levels of Ng may be associated with higher severity of NPS early in the AD continuum (age < 70). Furthermore, our data may indicate a potential relationship between the presence of NPS and synaptic as well as axonal degeneration in the setting of VaD pathology.

show abstract

“…In fact, neurogranin level is a predictor of the progressive decline of memory and executive function in patients with MCI, but not in elderly control subjects, indicating a potential disease-specific effect. 9 In support of this idea, CSF neurogranin was found to increase gradually in a normal elderly population without cognitive impairments, but did not change in patients with MCI or AD, which suggests that this is an early indicator. 8 It is apparent that neurogranin can predict cognitive decline and neurodegeneration; however, such exemplary studies have focused on CSF content.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 87%

Association between plasma exosome neurogranin and brain structure in patients with Alzheimer’s disease: a protocol study

Sun

Cao

et al. 2020

BMJ Open

View full text Add to dashboard Cite

IntroductionNeurogranin is known to be significantly elevated in patients with Alzheimer’s disease (AD) and may be an effective clinical predictor of cognitive decline and neurodegeneration. Amnestic mild cognitive impairment (aMCI) is an intermediate disease state between normal cognitive ageing and dementia, the latter of which can easily revert to AD. There remains significant uncertainty regarding the conversion of aMCI to AD, and therefore, elucidating such progression is paramount to the field of cognitive neuroscience. In this protocol study, we therefore aim to investigate the changes in plasma neurogranin in the early stage of AD and the mechanism thereof regarding the cognitive progression towards AD.Methods and analysisIn this study, patients with aMCI and AD patients (n=70 each) will be recruited at the memory clinic of the Department of Neurology of Hongqi Hospital affiliated with the Mudanjiang Medical University of China. Healthy older controls (n=70) will also be recruited from the community. All subjects will undergo neuroimaging and neuropsychological evaluations in addition to blood collection at the first year and the third year. We hope to identify a new biomarker of cognitive decline associated with AD and characterise its behaviour throughout the progression of aMCI to AD. This work will reveal novel targets for the therapeutic prevention, diagnosis and treatment of AD. The primary outcome measures will be (1) neuropsychological evaluation, including Mini-Mental State Examination, Montreal Cognitive Assessment, Clinical Dementia Rating scale, Shape Trail Test-A&B, Auditory Verbal Learning Test-HuaShan version; (2) microstructural alterations and hippocampal features from MRI scans; and (3) neurogranin levels in the neuronal-derived exosomes from peripheral blood samples.Ethics and disseminationThe ethics committee of the Hongqi Hospital affiliated with the Mudanjiang Medical University of China has approved this study protocol. The results will be published in peer-reviewed journals and presented at national or international scientific conferences.Trial registration numberChiCTR2000029055.

show abstract

Neurogranin as a predictor of memory and executive function decline in MCI patients

Cited by 48 publications

References 33 publications

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Differential effects of neurodegeneration biomarkers on subclinical cognitive decline

Are neuropsychiatric symptoms in dementia linked to CSF biomarkers of synaptic and axonal degeneration?

Association between plasma exosome neurogranin and brain structure in patients with Alzheimer’s disease: a protocol study

Contact Info

Product

Resources

About