CSF biomarkers in neurodegenerative and vascular dementias

Llorens, Franc; Schmitz, Matthias; Ferrer, Isidro; Zerr, Inga

doi:10.1016/j.pneurobio.2016.03.003

Cited by 35 publications

(21 citation statements)

References 334 publications

(360 reference statements)

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“…11,30,37 Clinical treatment for pre-clinical declines in cognition would be strengthened by effective biomarkers of dementia; this expanding area of research could also lead to longitudinal testing improvements in epidemiologic risk factor identification. 38–40 …”

Section: Discussionmentioning

confidence: 99%

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study

Farooqui

Bakulski

Power

et al. 2017

Environmental Research

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Background Lead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. Methods In a 1993–2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. Results Among men 51–98 at baseline, higher patella Pb concentration (IQR: 21 µg/g) was associated with −0.13 lower baseline MMSE (95% CI: −0.25, −0.004) and faster longitudinal MMSE decline (−0.016 units/year, 95% CI: −0.032, −0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: −0.026, −0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: −0.027, −0.002). We found weaker associations with tibia Pb. Conclusions Cumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging.

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Section: Discussionmentioning

confidence: 99%

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study

Farooqui

Bakulski

Power

et al. 2017

Environmental Research

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“…However, there is little doubt that analysing biomarkers improves AD diagnostic accuracy and may in future be markers of disease progression or outcome targets for clinical trials. There is a large number of potential biomarkers which represent neurodegeneration, amyloid precursor protein metabolism, tangle pathology, blood-brain-barrier function or glial activation due to inflammation (286). However, results tend to be from highly selected populations, that even a meta-analysis of many studies may produce overly optimistic performance results.…”

Section: Cerebrospinal Fluid and Blood Biomarkersmentioning

confidence: 99%

Dementia prevention, intervention, and care

et al. 2017

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People with dementia are usually older, often have co-morbidities and may need help in coping with these illnesses. A third of older people now die with dementia and all professionals working in endof-life care need to make this a central part of their planning and communication. In this commission, we have detailed evidence-based approaches to dementia and its symptoms. Services should be available, scalable and give value. As there are limited resources, professionals and services need to use what works, not use what is ineffective, and be aware of the difference. Overall, there is good potential for prevention and, once someone develops dementia, for care to be high-quality, accessible, and give value to an under-served, growing population. Effective dementia prevention and care could transform the future for society and vastly improve living and dying for individuals with dementia and their families. Acting now on what we already know can make this difference happen. Key Messages 1 There are increasing numbers of people with dementia globally although incidence in some countries has decreased. 2 Be ambitious about prevention: We recommend energetically treating hypertension in middle aged and older people without dementia to reduce dementia incidence. Interventions for other risk factors, including more childhood education, exercise, maintaining social engagement, reducing smoking, and management of hearing loss, depression, diabetes and obesity; may have the potential of delaying or preventing a third of dementias. 3 Treat cognitive symptoms: To maximise cognition, people with Alzheimer's dementia or Dementia with Lewy Bodies should be offered Cholinesterase Inhibitors (ChEIs)at all stages, or memantine for severe dementia. ChEIs are not effective in Mild Cognitive Impairment. 4 Individualise dementia care: Good dementia care spans medical, social and supportive care, should be tailored to unique individual and cultural needs, preferences, priorities, and should incorporate support for the family carers 5 Care for family carers. Family carers are at high risk of depression. Effective interventions reduce the risk and treat the symptoms, include START (Strategies for Relatives) or REACH (Resources for Enhancing Alzheimer's Caregiver Health intervention) and should be made available. 6 Plan for the future. People with dementia and their families value discussions about the future and decisions about possible attorneys to make decisions. Clinicians should consider capacity to make different types of decisions at diagnosis. 7 Protect people with dementia. People with dementia and society require protection from possible risks of the condition, including self-neglect, vulnerability including to exploitation, managing money, driving or using weapons. Risk assessment and management at all stages of the disease is essential but it should be balanced against the persons' right to autonomy. 8 Manage neuropsychiatric symptoms. Management of the neuropsychiatric symptoms of dementia including agitation, low mood or psyc...

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“…The early identification of WMH-CIND plays a vital role in the prevention of the onset and progression of CI and dementia. Several diagnostic approaches and potential detection methods have been developed (Van Maurik et al, 2017), including standard neuropsychological tests (Bai et al, 2010;Xu et al, 2010), neuroimaging markers (structural MRI markers, including those for hippocampal atrophy, ventricular volume and whole brain atrophy) and PET-CT markers (Nettiksimmons et al, 2010;Arbizu et al, 2018;Caminiti et al, 2018), electrophysiological tests (Imperatori et al, 2019) and biomarkers in cerebrospinal fluid (P-tau, tau, Aβ peptides, and Aβ42/P-tau ratio) (Van Harten et al, 2011;Llorens et al, 2016), with their respective strengths and weaknesses, as well as different prognostic accuracies and specificities. In recent years, resting-state fMRI (rs-fMRI) and diffusion MR markers have been increasingly used in the investigation of new markers of CI (Franzmeier et al, 2017).…”

Section: Clustering Analysis Based On Support Vector Machine and Automentioning

confidence: 99%

Nodal Global Efficiency in Front-Parietal Lobe Mediated Periventricular White Matter Hyperintensity (PWMH)-Related Cognitive Impairment

Chen

Huang

Yang

et al. 2019

Front. Aging Neurosci.

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White matter hyperintensity (WMH) is widely observed in the elderly population and serves as a key indicator of cognitive impairment (CI). However, the underlying mechanism remains to be elucidated. Herein, we investigated the topological patterns of resting state functional networks in WMH subjects and the relationship between the topological measures and CI. A graph theory-based analysis was employed in the resting-state functional magnetic resonance scans of 112 subjects (38 WMH subjects with cognitive impairment without dementia (CIND), 36 WMH subjects with normal cognition and 38 healthy controls (HCs), and we found that WMH-CIND subjects displayed decreased global efficiency at the levels of the whole brain, specific subnetworks [fronto-parietal network (FPN) and cingulo-opercular network (CON)] and certain nodes located in the FPN and CON, as well as decreased local efficiency in subnetworks. Our results demonstrated that nodal global efficiency in frontal and parietal regions mediated the impairment of information processing speed related to periventricular WMH (PWMH). Additionally, we performed support vector machine (SVM) analysis and found that altered functional efficiency can identify WMH-CIND subjects with high accuracy, sensitivity and specificity. These findings suggest impaired functional networks in WMH-CIND individuals and that decreased functional efficiency may be a feature of CI in WMH subjects.

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CSF biomarkers in neurodegenerative and vascular dementias

Cited by 35 publications

References 334 publications

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study

Dementia prevention, intervention, and care

Nodal Global Efficiency in Front-Parietal Lobe Mediated Periventricular White Matter Hyperintensity (PWMH)-Related Cognitive Impairment

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