scholarly journals Inflammatory Biomarkers Aid in Diagnosis of Dementia

2021 ◽  
Vol 13 ◽  
Author(s):  
Erik B. Erhardt ◽  
John C. Adair ◽  
Janice E. Knoefel ◽  
Arvind Caprihan ◽  
Jillian Prestopnik ◽  
...  

Dual pathology of Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID) commonly are found together at autopsy, but mixed dementia (MX) is difficult to diagnose during life. Biological criteria to diagnose AD have been defined, but are not available for vascular disease. We used the biological criteria for AD and white matter injury based on MRI to diagnose MX. Then we measured multiple biomarkers in CSF and blood with multiplex biomarker kits for proteases, angiogenic factors, and cytokines to explore pathophysiology in each group. Finally, we used machine learning with the Random forest algorithm to select the biomarkers of maximal importance; that analysis identified three proteases, matrix metalloproteinase-10 (MMP-10), MMP-3 and MMP-1; three angiogenic factors, VEGF-C, Tie-2 and PLGF, and three cytokines interleukin-2 (IL-2), IL-6, IL-13. To confirm the clinical importance of the variables, we showed that they correlated with results of neuropsychological testing.

2019 ◽  
Vol 9 (8) ◽  
pp. 187 ◽  
Author(s):  
Gary A. Rosenberg ◽  
Jillian Prestopnik ◽  
Janice Knoefel ◽  
John C. Adair ◽  
Jeffrey Thompson ◽  
...  

Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) are major causes of dementia, and when combined lead to accelerated cognitive loss. We hypothesized that biomarkers of neurodegeneration and neuroinflammation could be used to stratify patients into diagnostic groups. Diagnosis of AD can be made biologically with detection of amyloid and tau proteins in the cerebrospinal fluid (CSF) and vascular disease can be identified with diffusion tensor imaging (DTI). We recruited patients with cognitive complaints and made an initial clinical diagnosis. After one year of follow-up we made a biological diagnosis based on the use of biomarkers obtained from DTI, CSF AD, and inflammatory proteins, and neuropsychological testing. Patients with AD had primarily findings of neurodegeneration (CSF showing increased tau and reduced amyloid), while patients with neuroinflammation had abnormal DTI mean diffusion (MD) in the white matter. Using the biological biomarkers resulted in many of the clinically diagnosed AD patients moving into mixed dementia (MX). Biomarkers of inflammation tended to be higher in the MX than in either the AD or VCID, suggesting dual pathology leads to increased inflammation, which could explain accelerated cognitive decline in that group.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wolfgang Trapp ◽  
Susanne Röder ◽  
Andreas Heid ◽  
Pia Billman ◽  
Susanne Daiber ◽  
...  

Abstract Background Currently, many patients suffering from dementia do not have a diagnosis when admitted to geriatric hospitals. This is the case despite an increased risk of complications affecting the length of stay and outcome. Unfortunately, many dementia screening tests cannot be used on geriatric inpatients, who are often bedridden. Therefore, we aimed at evaluating the diagnostic accuracy of a small battery of bedside tasks that require minimal vision and fine motor skills in patients with suspected dementia. Methods In this prospective study, the Bamberg Dementia Screening Test (BDST) was administered to a consecutive series of 1295 patients referred for neuropsychological testing. The diagnosis of dementia was confirmed in 1159 and excluded in 136 patients. Sensitivity and specificity for the first subtest (ultra-short form), the first two subtests (short form), and the total score of the BDST were obtained via receiver operating characteristic curves and compared with the sensitivity and specificity values of the Mini-Mental Status Examination (MMSE). Results The overall diagnostic quality of the BDST was superior to the MMSE for mild Alzheimer’s dementia (sensitivity and specificity = .94 (95% CI .92 to .96) and .82 (95% CI .75 to .88) vs. .79 (95% CI .76 to .83) and .88 (95% CI .82 to .93)) as well as for other subtypes of mild dementia (sensitivity and specificity = .91 (95% CI .88 to .94) and .82 (95% CI .75 to .88) vs. .72 (95% CI .67 to .76) and .88 (95% CI .82 to .93)). Even the short form of the BDST was comparable to the MMSE regarding sensitivity and specificity. For moderate dementia, it was possible to identify dementia cases with sufficient and excellent diagnostic quality by using the ultra-short and the short form. Conclusions The BDST is able to detect dementia in geriatric hospital settings. If the adaptive algorithm is used, administration time can be reduced to less than 2 min in most cases. Because no test materials have to be exchanged, this test is particularly suitable for infectious environments where contact between the examiner and the person being tested should be minimized.


2018 ◽  
Vol 28 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Xin Zhang ◽  
Jiabin Su ◽  
Chao Gao ◽  
Wei Ni ◽  
Xinjie Gao ◽  
...  

Vascular cognitive impairment (VCI) defines an entire spectrum of neurologic disorders from mild cognitive impairment to dementia caused by cerebral vascular disease. The pathogenesis of VCI includes ischemic factors (e.g., large vessel occlusion and small vessel dysfunction); hemorrhagic factors (e.g., intracerebral hemorrhage and subarachnoid hemorrhage); and other factors (combined with Alzheimer’s disease). Clinical evaluations of VCI mainly refer to neuropsychological testing and imaging assessments, including structural and functional neuroimaging, with different advantages. At present, the main treatment for VCI focuses on neurological protection, cerebral blood flow reconstruction, and neurological rehabilitation, such as pharmacological treatment, revascularization, and cognitive training. In this review, we discuss the pathogenesis, neuroimaging evaluation, and treatment of VCI.


BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e040466
Author(s):  
Aravind Ganesh ◽  
Philip Barber ◽  
Sandra E Black ◽  
Dale Corbett ◽  
Thalia S Field ◽  
...  

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.


2014 ◽  
Vol 26 (5) ◽  
pp. 787-793 ◽  
Author(s):  
YanHong Dong ◽  
Melissa Jane Slavin ◽  
Bernard Poon-Lap Chan ◽  
Narayanaswamy Venketasubramanian ◽  
Vijay Kumar Sharma ◽  
...  

ABSTRACTBackground:The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were compared with and without the addition of a brief processing speed test, the symbol digit modalities test (SDMT), for vascular cognitive impairment (VCI) screening at three to six months after stroke.Methods:Patients with ischemic stroke and transient ischemic attack were assessed with MoCA and MMSE, as well as a formal neuropsychological battery three to six months after stroke. VCI was defined by impairment in any cognitive domain on neuropsychological testing. The area under the receiver operating characteristic curve (AUC) was used to compare test discriminatory ability.Results:One hundred and eighty-nine patients out of 327 (58%) had VCI, of whom 180 (95%) had vascular mild cognitive impairment (VaMCI), and nine (5%) had dementia. The overall AUCs of the MoCA and MMSE scores and performance at their respective cut-off points were equivalent in detecting VCI (AUCs: 0.87 (95% CI 0.83–0.91) vs. 0.84 (95% CI 0.80–0.88), p = 0.13; cut-offs: MoCA (≤23) vs. MMSE (≤26), sensitivity: 0.78 vs. 0.71; specificity: 0.80 vs. 0.82; positive predictive value: 0.84 vs. 0.84; negative predictive value: 0.72 vs. 0.67; and correctly classified 78.6% vs. 75.5%; p = 0.42). The AUCs of MMSE and MoCA were improved significantly by the SDMT (AUCs: MMSE+SDMT 0.90 (95% CI 0.87–0.93), p <0.001; MoCA+SDMT 0.91 (95% CI 0.88–0.94), p < 0.02).Conclusions:The MoCA and MMSE are equivalent and moderately sensitive, and can be supplemented with the SDMT to improve their accuracy in VCI screening.


Neurology ◽  
1998 ◽  
Vol 51 (2) ◽  
pp. 363-370 ◽  
Author(s):  
B. F. Boeve ◽  
M. H. Silber ◽  
T. J. Ferman ◽  
E. Kokmen ◽  
G. E. Smith ◽  
...  

Background:REM sleep behavior disorder (RBD) has been reported with various neurodegenerative disorders, most frequently in disorders with Lewy body pathology. RBD often precedes the onset of PD, and a recent prospective study showed that 38% of patients with RBD eventually developed PD.Methods:We identified 37 patients with degenerative dementia and a history of bursts of vigorous movement of the arms and legs with vocalization during sleep and associated with dream recall. Patients with and without two or more signs of parkinsonism were compared. Clinical, laboratory, and neuropsychometric features were analyzed, and criteria for the clinical diagnosis of dementia with Lewy bodies (DLB) were applied to all patients.Results:Thirty-four of the 37 patients were male with mean age at onset of 61.5 years for RBD and 68.1 years for cognitive decline. RBD commenced before or concurrently with dementia in all patients but two. Parkinsonism (two or more signs) occurred in 54% of the sample (20/37), with a mean age at onset of 69.1 years. Polysomnography (PSG) confirmed RBD in all patients studied. Neuropsychological testing demonstrated impaired perceptual-organizational skills, verbal fluency, and marked constructional dyspraxia in more than one-half the patients. There were no statistically significant differences in the frequency of clinical features or in neuropsychological performance between patients with and without parkinsonism. Thirty-four patients (92%) met criteria for clinically possible or probably DLB. Three patients were autopsied; all had limbic with or without neocortical Lewy bodies.Conclusions:We report a group of predominantly male patients with a characteristic association of RBD and degenerative dementia. The clinical and neuropsychometric features of the groups of patients with and without parkinsonism are similar. We hypothesize that the underlying pathology in these patients is DLB.


1998 ◽  
Vol 10 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Kenneth Rockwood ◽  
Kellee Howard ◽  
Vince Salazar Thomas ◽  
Laurie Mallery ◽  
Christopher Macknight ◽  
...  

The accuracy of a dementia diagnosis by specialist physicians, as verified at an autopsy, is greater than 90% in many series. Donations of brains to the Maritime Brain Tissue Bank (MBTB) by individuals who did not have expert dementia diagnoses before death led us to investigate whether clinical features could also be detected retrospectively. Informants for 36 individuals whose brains were in the MBTB (18 women, mean age = 79 years; pathologic diagnoses: 75% Alzheimer's disease [AD]; 8.4% vascular or mixed dementia) were interviewed by specialist physicians using a semistructured retrospective interview based on the Brief Cognitive Rating Scale (BCRS) (range = 1 [no impairment] to 7 [terminal dementia]). The mean duration of dementia was 8.5 ± 12.8 years based on proxy reports, and most cases suggested severe dementia—(stage 6 [severe] or 7 [terminal])—on the retrospective BCRS (RetroBCRS) before death. A score of 4 or more on the RetroBCRS had 100% sensitivity and specificity in detecting dementia. The RetroBCRS score correlated moderately with duration (.51). In linear and logistic regression models adjusted for age and sex, RetroBCRS staging helped explain 93% of the variation in duration. The accuracy of the retrospective diagnosis of the cause of dementia, compared with autopsy, was 92%. The RetroBCRS used by an expert physician with a reliable informant is a valid method of detecting dementia and determining whether AD was present.


2012 ◽  
Vol 6 (3) ◽  
pp. 192-195
Author(s):  
José Ibiapina Siqueira- Neto ◽  
Paulo Marcelo Gondim Sales ◽  
Emmanuelle Silva Tavares Sobreira ◽  
Aline Miranda Limeira ◽  
Heline Bessa Araujo ◽  
...  

ABSTRACT Pemphigus vulgaris is a systemic auto-immune medical condition that mainly manifests with changes in skin and vasculopathy. This is a case report of a 69-year-old male with confirmed histopathologic diagnosis of Pemphigus vulgaris presenting ulterior Cognitive Impairment, mostly in executive function. The patient was treated using steroids, immunomodulatory therapy, fluoxetine and galantamine. Neuropsychological testing and magnetic resonance (MRI) were performed. This is the first report of correlational cognitive impairment with Pemphigus vulgaris in the literature. Physicians should be aware of vascular causes for cognitive impairment in patients presenting auto-immune conditions.


2015 ◽  
Vol 7s1 ◽  
pp. BIC.S25250 ◽  
Author(s):  
Luay Mousa ◽  
Mohamed E. Salem ◽  
Sameh Mikhail

Colorectal cancer (CRC) is the third most common cancer worldwide and accounts for 10% of all new cancer diagnoses. Angiogenesis is a tightly regulated process that is mediated by a group of angiogenic factors such as vascular endothelial growth factor and its receptors. Given the widespread use of antiangiogenic agents in CRC, there has been considerable interest in the development of methods to identify novel markers that can predict outcome in the treatment of this disease with angiogenesis inhibitors. Multiple biomarkers are in various phases of development and include tissue, serum, and imaging biomarkers. The complexity of the angiogenesis pathway and the overlap between the various angiogenic factors present a significant challenge to biomarker discovery. In our review, we discuss the angiogenesis pathway and the most promising evolving concepts in biomarker discovery, as well as highlight the landmark studies that identify subgroups of patients with CRC who may preferentially benefit from angiogenesis inhibitors.


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