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

Bloniecki, Victor; Zetterberg, Henrik; Aarsland, Dag; Vannini, Patrizia; Kvartsberg, Hlin; Winblad, Bengt; Blennow, Kaj; Freund‐Levi, Yvonne

doi:10.1186/s13195-020-00718-y

Cited by 10 publications

(7 citation statements)

References 69 publications

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“…In AD patients, higher plasma NfL levels have been shown to be associated with poorer Mini Mental State Examination (MMSE) scores [ 15 ], and plasma Nfl and CSF NfL levels are the best single predictors of cognition in AD patients [ 16 ]. On the other hand, a recent study found no significant correlation between neuropsychiatric symptoms and CSF NfL in AD [ 17 ]. For vascular dementia, however, there was a negative correlation between CSF NfL and neuropsychiatric performance [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients

Lukkarinen

Jeppsson

Wikkelsø

et al. 2022

Fluids Barriers CNS

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Background The relationship between cerebrospinal fluid (CSF) biomarkers and the clinical features of idiopathic normal pressure hydrocephalus (iNPH) has been inconclusive. We aimed to evaluate CSF biomarkers reflecting Alzheimer’s disease (AD)-related amyloid β (Aβ) aggregation, tau pathology, neuroinflammation and axonal degeneration in relation to the clinical features of pre- and post-shunt surgery in iNPH patients. Methods Mini Mental State Examination (MMSE) scores and gait velocity were evaluated pre- and postoperatively in cohorts of 65 Finnish (FIN) and 82 Swedish (SWE) iNPH patients. Lumbar CSF samples were obtained prior to shunt surgery and analysed for soluble amyloid precursor protein alpha (sAPPα) and beta (sAPPβ); amyloid-β isoforms of 42, 40 and 38 (Aβ42, Aβ40, Aβ38); total tau (T-tau); phosphorylated tau (P-tau181); neurofilament light (NfL) and monocyte chemoattractant protein 1 (MCP1). Results Preoperative patient characteristics showed no significant differences between patients in the FIN and SWE cohorts. Patients in both cohorts had significantly improved gait velocity after shunt surgery (p < 0.0001). Low CSF T-tau and absence of apolipoprotein E ε4 predicted over 20% gait improvement postoperatively (p = 0.043 and p = 0.008). Preoperative CSF T-tau, P-tau181 and NfL correlated negatively with MMSE scores both pre- (p < 0.01) and post-surgery (p < 0.01). Furthermore, T-tau, NfL and Aβ42 correlated with MMSE outcomes (p < 0.05). Low preoperative CSF P-tau181 (p = 0.001) and T-tau with NfL (p < 0.001 and p = 0.049) best predicted pre- and postoperative MMSE scores greater than or equal to 26. Conclusions CSF biomarkers of neurodegeneration appeared to correlate with pre- and postoperative cognition, providing a window into neuropathological processes. In addition, preoperative CSF neurodegeneration biomarkers may have potential in the prediction of gait and cognitive outcomes after shunt surgery.

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Section: Introductionmentioning

confidence: 99%

“…On the other hand, a recent study found no significant correlation between neuropsychiatric symptoms and CSF NfL in AD [ 17 ]. For vascular dementia, however, there was a negative correlation between CSF NfL and neuropsychiatric performance [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients

Lukkarinen

Jeppsson

Wikkelsø

et al. 2022

Fluids Barriers CNS

Self Cite

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“…The correlation was modest, yet independent of age and sex. So far, only one other study has examined the relationship between CSF, NfL, and neuropsychiatric symptoms in AD patients and failed to observe a significant correlation [ 34 ]. It is unclear whether sNfL is directly related to neuropsychiatric symptomatology or the association is indirect because behavioural abnormalities indicate faster decline of cognitive functions [ 17 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria

et al. 2022

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Background and Objectives: The neurofilament light chain (NfL) is a biomarker for neuro-axonal injury in various acute and chronic neurological disorders, including Alzheimer’s disease (AD). We here investigated the cross-sectional and longitudinal associations between baseline serum NfL (sNfL) levels and cognitive, behavioural as well as MR volumetric findings in the Prospective Dementia Registry Austria (PRODEM-Austria). Materials and Methods: All participants were clinically diagnosed with AD according to NINCDS-ADRDA criteria and underwent a detailed clinical assessment, cognitive testing (including the Mini Mental State Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD)), the neuropsychiatric inventory (NPI) and laboratory evaluation. A total of 237 patients were included in the study. Follow-up examinations were done at 6 months, 1 year and 2 years with 93.3% of patients undergoing at least one follow-up. We quantified sNfL by a single molecule array (Simoa). In a subgroup of 125 subjects, brain imaging data (1.5 or 3T MRI, with 1 mm isotropic resolution) were available. Brain volumetry was assessed using the FreeSurfer image analysis suite (v6.0). Results: Higher sNfL concentrations were associated with worse performance in cognitive tests at baseline, including CERAD (B = −10.084, SE = 2.999, p < 0.001) and MMSE (B = −3.014, SE = 1.293, p = 0.021). The sNfL levels also correlated with the presence of neuropsychiatric symptoms (NPI total score: r = 0.138, p = 0.041) and with smaller volumes of the temporal lobe (B = −0.012, SE = 0.003, p = 0.001), the hippocampus (B = −0.001, SE = 0.000201, p = 0.013), the entorhinal (B = −0.000308, SE = 0.000124, p = 0.014), and the parahippocampal cortex (B = −0.000316, SE = 0.000113, p = 0.006). The sNfL values predicted more pronounced cognitive decline over the mean follow-up period of 22 months, but there were no significant associations with respect to change in neuropsychiatric symptoms and brain volumetric measures. Conclusions: the sNfL levels relate to cognitive, behavioural, and imaging hallmarks of AD and predicts short term cognitive decline.

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“…This in particular is the case of diagnosis: O often inadequate when based only on medical practice, it has been recently improved by the multiplicity and specificity of biomarkers. By the use of the latter, it has been established that a disease can be diagnosed even before the appearance of symptoms [ 10 , 11 , 51 , 52 ]. Moreover, the intensity of the responses can contribute to the prognosis of patients [ 28 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Specific biomarkers have been applied not only to mature patients, but also to patients at early stages of disease. By novel and innovated methods, it could be established whether patients at risk of long-term diseases, such as AD or dementia, can be treated only upon full development of their symptoms, or also when symptoms are absent or still at an early stage [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Meldolesi

2021

Biomedicines

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Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

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

Cited by 10 publications

References 69 publications

Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients

Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients

Serum NfL in Alzheimer Dementia: Results of the Prospective Dementia Registry Austria

News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

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