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      Correlation between CSF biomarkers of Alzheimer’s disease and global cognition in a psychogeriatric clinic cohort

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          Abstract

          Objective:

          The relationship between biomarkers of amyloid-beta aggregation (Aβ 1-42) and/or neurodegeneration (Tau protein) in cerebrospinal fluid (CSF) and cognitive decline is still unclear. We aimed to ascertain whether CSF biomarkers correlate with cognitive performance in healthy and cognitively impaired subjects, starting from clinical diagnoses.

          Methods:

          We tested for correlation between CSF biomarkers and Mini-Mental State Examination (MMSE) scores in 208 subjects: 54 healthy controls, 82 with mild cognitive impairment (MCI), 46 with Alzheimer’s disease (AD), and 26 with other dementias (OD).

          Results:

          MMSE correlated weakly with all CSF biomarkers in the overall sample (r = 0.242, p < 0.0006). Aβ 1-42 and MMSE correlated weakly in MCI (r = 0.247, p = 0.030), and moderately in OD (r = 0.440, p = 0.027). t-Tau showed a weak inverse correlation with MMSE in controls (r = -0.284, p = 0.043) and MCI (r = -0.241, p = 0.036), and a moderate/strong correlation in OD (r = 0.665), p = 0.0003). p-Tau correlated weakly with MMSE in AD (r = -0.343, p = 0.026) and moderately in OD (r = -0.540, p = 0.0005). The Aβ 1-42/p-Tau ratio had a moderate/strong correlation with MMSE in OD (r = 0.597, p = 0.001).

          Conclusion:

          CSF biomarkers correlated best with cognitive performance in OD. t-Tau correlated weakly with cognition in controls and patients with MCI. In AD, only p-Tau levels correlated with cognitive performance. This pattern, which has been reported previously, seems to indicate that CSF biomarkers might not be reliable as indicators of disease severity.

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          Most cited references30

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          Dementia in Latin America: Epidemiological Evidence and Implications for Public Policy

          Population aging is among the most important global transformations. Today, 12% of the world population is of age 60 and over and by the middle of this century this segment will represent 21.5%. The increase in population of those aged 80 and over, also referred to as the “oldest old” or the “very elderly”, will be even more pronounced, going from 1.7% of the population to 4.5% within the same period. Compared to European and North American countries, Latin America (LA) is experiencing this unprecedented demographic change at a significantly faster rate. Due to demographic and health transitions, the number of people with dementia will rise from 7.8 million in 2013 to over 27 million by 2050. Nowadays, the global prevalence of dementia in LA has reached 7.1%, with Alzheimer’s Disease (AD) being the most frequent type. This level is similar to those found in developed countries; however, the dementia rate is twice as high as that of the 65–69 years age group in developed countries. In addition, the prevalence and incidence of dementia is higher among illiterate people. Mortality rates due to dementia have risen considerably. The burden and costs of the disease are high and must be covered by patients’ families. The prevention of dementia and the development of long-term care policies and plans for people with dementia in LA, which take into account regional differences and similarities, should be urgent priorities.
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            Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia.

            This article presents recommendations, based on the Grading of Recommendations, Assessment, Development, and Evaluation method, for the clinical application of cerebrospinal fluid (CSF) amyloid-β1-42, tau, and phosphorylated tau in the diagnostic evaluation of patients with dementia. The recommendations were developed by a multidisciplinary working group based on the available evidence and consensus from focused discussions for (i) identification of Alzheimer's disease (AD) as the cause of dementia, (ii) prediction of rate of decline, (iii) cost-effectiveness, and (iv) interpretation of results. The working group found sufficient evidence to support a recommendation to use CSF AD biomarkers as a supplement to clinical evaluation, particularly in uncertain and atypical cases, to identify or exclude AD as the cause of dementia. Because of insufficient evidence, it was uncertain whether CSF AD biomarkers outperform imaging biomarkers. Operational recommendations for the interpretation of ambiguous CSF biomarker results were also provided.
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              Meta-Review of CSF Core Biomarkers in Alzheimer’s Disease: The State-of-the-Art after the New Revised Diagnostic Criteria

              Background: Current research criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers into the diagnostic algorithm. However, spreading their use to the clinical routine is still questionable. Objective: To provide an updated, systematic and critical review on the diagnostic utility of the CSF core biomarkers for AD. Data sources: MEDLINE, PreMedline, EMBASE, PsycInfo, CINAHL, Cochrane Library, and CRD. Eligibility criteria: (1a) Systematic reviews with meta-analysis; (1b) Primary studies published after the new revised diagnostic criteria; (2) Evaluation of the diagnostic performance of at least one CSF core biomarker. Results: The diagnostic performance of CSF biomarkers is generally satisfactory. They are optimal for discriminating AD patients from healthy controls. Their combination may also be suitable for mild cognitive impairment (MCI) prognosis. However, CSF biomarkers fail to distinguish AD from other forms of dementia. Limitations: (1) Use of clinical diagnosis as standard instead of pathological postmortem confirmation; (2) variability of methodological aspects; (3) insufficiently long follow-up periods in MCI studies; and (4) lower diagnostic accuracy in primary care compared with memory clinics. Conclusion: Additional work needs to be done to validate the application of CSF core biomarkers as they are proposed in the new revised diagnostic criteria. The use of CSF core biomarkers in clinical routine is more likely if these limitations are overcome. Early diagnosis is going to be of utmost importance when effective pharmacological treatment will be available and the CSF core biomarkers can also be implemented in clinical trials for drug development.
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                Author and article information

                Journal
                Braz J Psychiatry
                Braz J Psychiatry
                bjp
                Brazilian Journal of Psychiatry
                Associação Brasileira de Psiquiatria
                1516-4446
                1809-452X
                30 May 2019
                Nov-Dec 2019
                : 41
                : 6
                : 479-484
                Affiliations
                [1]Laboratório de Neurociências (LIM-27), Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil
                Author notes
                Correspondence: Márcia Radanovic, Departamento de Psiquiatria, Universidade de Sao Paulo, Rua Dr. Ovidio Pires de Campos, 785, CEP 05403-010, Sao Paulo, SP, Brazil. E-mail: marciaradanovic@ 123456gmail.com
                Author information
                http://orcid.org/0000-0002-3256-6397
                Article
                10.1590/1516-4446-2018-0296
                6899355
                31166546
                7640e528-bde0-456e-88d8-806a063978b5

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 October 2018
                : 5 February 2019
                Categories
                Original Article

                mild cognitive impairment,dementia,alzheimer’s disease,cerebrospinal fluid biomarkers

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