Neuropsychological and behavioural correlates of CSF biomarkers in dementia

Engelborghs, Sebastiaan; Maertens, Karen; Vloeberghs, Ellen; Aerts, Tony; Somers, Nore; Mariën, Peter; Deyn, Peter Paul De

doi:10.1016/j.neuint.2005.11.002

Cited by 61 publications

(50 citation statements)

References 57 publications

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“…Greater numbers of amyloid plaques and neurofibrillary tangles have been described in depressed participants at autopsy. [15][16][17] However, varying cross-sectional studies show that the biomarker CSF b-amyloid 1-42 is increased, 18 decreased, 19 and unrelated 20 to depression. Similarly, studies examining the association between psychological and cognitive symptoms have borne variable results.…”

mentioning

confidence: 99%

“Noncognitive” symptoms of early Alzheimer disease

Masters¹,

Morris²,

Roe³

2015

Neurology

159

117

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Objectives: To observe the natural time course of noncognitive symptoms before the onset of symptomatic Alzheimer disease dementia.Methods: Using the National Alzheimer's Coordinating Center Uniform Data Set from September 2005 to March 2013, data from cognitively normal individuals who were aged 50 years or older at first visit and had subsequent follow-up were analyzed. Survival analyses were used to examine the development of particular symptoms relative to each other on the Neuropsychiatric Inventory Questionnaire (NPI-Q), Functional Activities Questionnaire, and Geriatric Depression Scale, and to compare the development of individual symptoms for persons who did and did not receive a Clinical Dementia Rating (CDR) .0 (indicating abnormal cognition) during the follow-up period.Results: The order of symptom occurrence on the NPI-Q was similar for participants who remained at CDR 0 and for those who received a CDR .0 over the follow-up period, although the time to most NPI-Q symptoms was faster for participants who received a CDR .0 (p , 0.001). With the exception of memory, Geriatric Depression Scale symptoms reported by both CDR groups were similar. Conclusions:We found a significantly earlier presence of positive symptoms on the NPI-Q in cognitively normal patients who subsequently developed CDR .0. Among participants with no depression symptoms at baseline, results suggest that depressive symptoms may increase with aging regardless of incipient dementia. Such findings begin to delineate the noncognitive course of Alzheimer disease dementia in the preclinical stages. Future research must further elucidate the correlation between noncognitive changes and distinct dementia subtypes. The natural course of Alzheimer disease (AD) dementia includes hallmark functional and behavioral deficits in addition to cognitive decline. Alternately termed behavioral and psychological symptoms in dementia or neuropsychiatric symptoms (NPS), this heterogeneous array of noncognitive impairment affects an estimated 90% of patients with AD.1 Earlier studies have shown that with advancing cognitive decline in AD dementia, noncognitive symptoms include apathy, depression, agitation, and aggression, to psychosis. With progressive cognitive and functional decline in AD dementia, the presence of NPS is postulated to represent increased neurodegradation across neural systems.2-5 Such NPS have been associated with worse prognosis, accelerated illness progression, increased use of services, and earlier institutionalization.2 However, variable neuropsychiatric measures and clinical definitions have clouded the true incidence and progression of NPS in patients with AD.While noncognitive outcomes of AD after incident dementia are increasingly characterized, the relative time course of behavioral and functional deficits before onset of cognitive impairment in AD dementia has been rarely studied. Here, we examined the time course of noncognitive symptoms reported on the Functional Activities Questionnaire (FAQ), 6 Geriatric Depression

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confidence: 99%

“Noncognitive” symptoms of early Alzheimer disease

Masters¹,

Morris²,

Roe³

2015

Neurology

159

117

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“…14 Cross-sectional studies show conflicting results regarding mood, with reports that CSF Ab 42 is increased, 15 decreased, 16 and unrelated 14 to depression. However, depression has been found to be associated with greater numbers of amyloid plaques 17,18 and neurofibrillary tangles at autopsy.…”

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confidence: 99%

CSF biomarkers of Alzheimer disease

et al. 2013

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“…It has been successfully used to categorize subjects by disease status (3,4,15,16) and has the potential to be an FDA-approved diagnostic test for AD. There is also growing interest in using these types of kits to measure CSF Aβ 42 changes as a pharmacodynamic biomarker of drug effect in clinical trials (23,24).…”

Section: General Observations On the Use Of Aβ 42 Assays In The Fieldmentioning

confidence: 99%

“…Amongst the main concerns has been how to predict who will succumb to AD and how to monitor clinical improvement during therapeutic intervention. To this end, AD biomarkers have received much attention, including CSF amyloid beta 42 (Aβ 42 ), which is lower in AD patients than in normal controls (1)(2)(3)(4)(5)(6). Low CSF Aβ 42 levels also predict conversion from mild cognitive impairment (MCI) to AD (7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Development and Advanced Validation of an Optimized Method for the Quantitation of Aβ42 in Human Cerebrospinal Fluid

Cullen¹,

Fredenburg²,

Evans³

et al. 2012

AAPS J

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Abstract. Cerebrospinal fluid (CSF) biomarkers have been extensively utilized in the diagnosis of Alzheimer's disease (AD) and characterization of progression. One important CSF biomarker is the amyloid beta 42 (Aβ 42 ) peptide, a key player in AD pathogenesis. The INNOTEST® Aβ 42 ELISA kit has been widely used but an advanced level of method development and validation has not been reported. To support a clinical trial in AD, we successfully completed a Good Laboratory Practices (GLP)-level validation of the method to establish the parameters of precision, accuracy, parallelism, selectivity, specificity, and linearity of dilution of the assay in CSF matrix, as well as CSF storage stability. Several modifications were required to optimize the assay and ensure consistent results in a clinical-trial setting. These included the use of additional calibrators, an adjusted standard curve range, a minimum required dilution (MRD) of CSF by 6-fold to avoid matrix interference and mitigation of analyte adsorption to labware by the addition of Tween-20. The optimized method displayed a quantitative range of 375-4,500 pg/mL. The inter-assay precision was ≤12.1 % CV and the inter-assay relative accuracy was ≤10.9 % absolute bias, bringing the total error of the assay to ≤23 %. The intra-assay precision of the assay at the high validation standard and below was ≤5.5 % CV; this enables sensitive detection of biomarker changes across a therapeutic regime. The INNOTEST® Aβ 42 ELISA kit, modified as reported here, may be appropriate for many applications, including regulatory agency acceptable clinical diagnosis and pharmacodynamic assessment.

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Neuropsychological and behavioural correlates of CSF biomarkers in dementia

Cited by 61 publications

References 57 publications

“Noncognitive” symptoms of early Alzheimer disease

“Noncognitive” symptoms of early Alzheimer disease

CSF biomarkers of Alzheimer disease

Development and Advanced Validation of an Optimized Method for the Quantitation of Aβ42 in Human Cerebrospinal Fluid

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