Cerebrospinal fluid neurofilament light and cerebral atrophy in younger‐onset dementia and primary psychiatric disorders

Walia, Nirbaanjot; Eratne, Dhamidhu; Loi, Samantha M; Farrand, Sarah; Li, Qiao‐Xin; Malpas, Charles; Varghese, Shiji; Walterfang, Mark; Evans, Andrew; Parker, Shaun; Collins, Steven J.; Masters, Colin L.; Velakoulis, Dennis

doi:10.1111/imj.15956

Cited by 3 publications

(2 citation statements)

References 30 publications

(67 reference statements)

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“…ADNI provides evidence of increased brain atrophy in several frontal brain areas. In addition, there is available data suggesting a direct association between the neuropsychiatric symptoms manifested by patients with AD and brain morphology changes, mainly atrophy of the frontotemporal brain structures (48)(49)(50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

“…The complex relationship linking dementia and depression has several underlying neuropathological mechanisms, such as increased hippocampal alterations and tangle formation in patients with AD and a history of depression (49)(50)(51)(52)(53). In addition, decreased cortical thickness, white matter loss and alterations in the hippocampal region were associated with both depressive symptoms and impairment of cognitive functions (49)(50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

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Early depressive manifestations in patients with dementia caused by Alzheimer's disease

Sârbu,

Lungu,

Oprea

et al. 2023

Exp Ther Med

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Previous studies on the complex interplay between depression and dementia in patients with Alzheimer's disease revealed that early-life depression is a risk factor for dementia. Both depression and dementia appear to share common etiopathological mechanisms. In the present study, a comprehensive retrospective analysis was performed on a study group of patients with dementia suffering from previously diagnosed depression. The aim was to assess potentially relevant clinical and imaging parameters that can be used to characterize depression as a risk factor for dementia in later life. Statistically significant data correlating cognitive scores with the moment of depression onset and the length of time period to the diagnosis of dementia were identified. Furthermore, at the moment of depression diagnosis, structural cerebral alterations tended to appear more frequently in women compared with men. However, this sex-associated difference is not maintained after the moment of dementia diagnosis. Results from the present study contributed additional data to the evidence supporting a relationship between a history of depression and the occurrence of Alzheimer's disease, discussing relevant clinical and imaging parameters featured in patients with dementia and their inter-relations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Early depressive manifestations in patients with dementia caused by Alzheimer's disease

Sârbu,

Lungu,

Oprea

et al. 2023

Exp Ther Med

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Neurofilament light-chain (NfL) and 18 kDa translocator protein in early psychosis and its putative high-risk

Nisha Aji,

Cisbani,

Weidenauer

et al. 2024

Brain, Behavior, & Immunity - Health

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The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer’s disease

Das,

van Engelen,

Goossens

et al. 2024

Alz Res Therapy

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Background Lack of early molecular biomarkers in sporadic behavioral variants of frontotemporal dementia (bvFTD) and its clinical overlap with primary psychiatric disorders (PPD) hampers its diagnostic distinction. Synaptic dysfunction is an early feature in bvFTD and identification of specific biomarkers might improve its diagnostic accuracy. Our goal was to understand the differential diagnostic potential of cerebrospinal fluid (CSF) synaptic biomarkers in bvFTD versus PPD and their specificity towards bvFTD compared with Alzheimer’s disease (AD) and controls. Additionally, we explored the association of CSF synaptic biomarkers with social cognition, cognitive performance, and disease severity in these clinical groups. Methods Participants with probable bvFTD (n = 57), PPD (n = 71), AD (n = 60), and cognitively normal controls (n = 39) with available CSF, cognitive tests, and disease severity as frontotemporal lobar degeneration-modified clinical dementia rating scale (FTLD-CDR) were included. In a subset of bvFTD and PPD cases, Ekman 60 faces test scores for social cognition were available. CSF synaptosomal-associated protein 25 (SNAP25), neurogranin (Ng), neuronal pentraxin 2 (NPTX2), and glutamate receptor 4 (GluR4) were measured, along with neurofilament light (NfL), and compared between groups using analysis of covariance (ANCOVA) and logistic regression. Diagnostic accuracy was assessed using ROC analyses, and biomarker panels were selected using Wald’s backward selection. Correlations with cognitive measures were performed using Pearson’s partial correlation analysis. Results NPTX2 concentrations were lower in the bvFTD group compared with PPD (p < 0.001) and controls (p = 0.003) but not compared with AD. Concentrations of SNAP25 (p < 0.001) and Ng (p < 0.001) were elevated in patients with AD versus those with bvFTD and controls. The modeled panel for differential diagnosis of bvFTD versus PPD consisted of NfL and NPTX2 (AUC = 0.96, CI: 0.93–0.99, p < 0.001). In bvFTD versus AD, the modeled panel consisted of NfL, SNAP25, Ng, and GluR4 (AUC = 0.86, CI: 0.79–0.92, p < 0.001). In bvFTD, lower NPTX2 (Pearson’s r = 0.29, p = 0.036) and GluR4 (Pearson’s r = 0.34, p = 0.014) concentrations were weakly associated with worse performance of total cognitive score. Lower GluR4 concentrations were also associated with worse MMSE scores (Pearson’s r = 0.41, p = 0.002) as well as with worse executive functioning (Pearson’s r = 0.36, p = 0.011) in bvFTD. There were no associations between synaptic markers and social cognition or disease severity in bvFTD. Conclusion Our findings of involvement of NTPX2 in bvFTD but not PPD contribute towards better understanding of bvFTD disease pathology.

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Cerebrospinal fluid neurofilament light and cerebral atrophy in younger‐onset dementia and primary psychiatric disorders

Cited by 3 publications

References 30 publications

Early depressive manifestations in patients with dementia caused by Alzheimer's disease

Early depressive manifestations in patients with dementia caused by Alzheimer's disease

Neurofilament light-chain (NfL) and 18 kDa translocator protein in early psychosis and its putative high-risk

The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer’s disease

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