Diagnosing Dementia in the Clinical Setting: Can Amyloid PET Provide Additional Value Over Cerebrospinal Fluid?
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ABSTRACT:
SUBMITTER: Weston PS
PROVIDER: S-EPMC5181662 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
Publications
Diagnosing Dementia in the Clinical Setting: Can Amyloid PET Provide Additional Value Over Cerebrospinal Fluid?
Weston Philip S J PS Paterson Ross W RW Dickson John J Barnes Anna A Bomanji Jamshed B JB Kayani Irfan I Lunn Michael P MP Mummery Catherine J CJ Warren Jason D JD Rossor Martin N MN Fox Nick C NC Zetterberg Henrik H Schott Jonathan M JM
Journal of Alzheimer's disease : JAD 20161001 4
Cerebrospinal fluid (CSF) measures of amyloid and tau are the first-line Alzheimer's disease biomarkers in many clinical centers. We assessed if and when the addition of amyloid PET following CSF measurements provides added diagnostic value. Twenty patients from a cognitive clinic, who had undergone detailed assessment including CSF measures, went on to have amyloid PET. The treating neurologist's working diagnosis, and degree of diagnostic certainty, was assessed both before and after the PET. ...[more]
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Project description:BackgroundOne of the major challenges in diagnosing dementia with Lewy bodies (DLB) is the common co-morbid presence of amyloid pathology. To understand the putative role of altered amyloid-? (A?) metabolism in dementia with DLB, we analyzed levels of different cerebrospinal fluid (CSF) A? peptides (A?38, A?40, A?42) in DLB, Alzheimer's disease (AD), and cognitively normal controls.MethodsCSF from patients with DLB (n =?72; age 68?±?6?years; 10%F; Mini-mental State examination (MMSE) 23?±?4), AD (n =?38; age 68?±?6?years; 8%F; MMSE 22?±?5), and cognitively normal controls (n =?38; age 67?±?7?years; 13%F; MMSE 29?±?2) was analyzed using the Meso Scale Discovery assay for human A? peptides. We performed general linear models to compare CSF A? peptide levels between groups. Associations between CSF A? peptides and MMSE score at baseline and longitudinal changes over time were assessed with linear mixed models.ResultsFor all three CSF A? peptides and compared to controls (A?38 2676?±?703?pg/ml, A?40 6243?±?1500?pg/ml, and A?42 692?±?205?pg/ml), we observed lower levels in DLB (A?38 2247?±?638, A?40 5432?±?1340, and A?42 441?±?185, p <?0.05), whereas AD patients showed only lower A?42 levels (304?±?71, p <?0.001). The observed differences in A?38 and A?40 were independent of co-morbid AD pathology (CSF tau/A?42?>?0.52) and APOE genotype. Finally, lower A? peptide levels were associated with lower MMSE score (? =?1.02-1.11, p <?0.05).ConclusionWe demonstrated different profiles of CSF A? reduction in DLB and AD. In particular, while AD is characterized by an isolated drop in A?42, DLB comes with reductions in A?38, A?40, and A?42. This suggests that amyloid metabolism is affected in DLB, even in the absence of co-morbid AD pathology.
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Project description:ObjectiveThe primary study objective of this retrospective academic memory clinic-based observational longitudinal study was to investigate the prognostic value of a cerebrospinal fluid (CSF)-based ATN classification for subsequent cognitive decline during the 3 years following lumbar puncture in a clinical, real-life setting. The secondary objective was to investigate the prognostic value of CSF biomarkers as continuous variables.MethodsData from 228 patients (median age 67 (47-85) years), who presented at the Neurology Memory Clinic UZ/KU Leuven between September 2011 and December 2016, were included with a follow-up period of up to 36 months. Patients underwent a CSF AD biomarker test for amyloid-beta 1-42 (Aβ42), hyperphosphorylated tau (p181-tau) and total tau (t-tau) in the clinical work-up for diagnostic reasons. Patients were divided into ATN classes based on CSF biomarkers: Aβ42 for amyloid (A), p181-tau for tau (T), and t-tau as a measure for neurodegeneration (N). Based on retrospective data analysis, cognitive performance was evaluated by Mini Mental State Examination (MMSE) scores every 6 months over a period up to 36 months following the lumbar puncture. The statistical analysis was based on linear mixed-effects modeling (LME).ResultsThe distribution in the current clinical sample was as follows: A-/T-/N- 32.02%, A+/T-/N- 33.33%, A+/T+/N+ 17.11%, A+/T-/N+ 11.84%, A-/T-/N+ 4.39%, A-/T+/N+ 1.32% (3 cases), with no cases in the A-/T+/N- and A+/T+/N- class. Hence, the latter 3 classes were excluded from further analyses. The change of MMSE relative to A-/T-/N- over a 36-month period was significant in all four ATN classes: A+/T+/N+ = - 4.78 points on the MMSE; A-/T-/N+ = - 4.76; A+/T-/N+ = - 2.83; A+/T-/N- = - 1.96. The earliest significant difference was seen in the A+/T+/N+ class at 12 months after baseline. The effect of ATN class on future cognitive decline was confirmed for a different set of CSF thresholds. All individual baseline CSF biomarkers including the Aβ42/t-tau ratio showed a significant correlation with subsequent cognitive decline, with the highest correlation seen for Aβ42/t-tau.ConclusionATN classification based on CSF biomarkers has a statistically significant and clinically relevant prognostic value for the course of cognitive decline in a 3-year period in a clinical practice setting.
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Project description:Cerebral amyloid angiopathy is caused by deposition of the amyloid beta protein in the cerebral vasculature. In analogy to previous observations in Alzheimer disease, we hypothesized that analysis of amyloid beta(40) and beta(42) proteins in the cerebrospinal fluid might serve as a molecular biomarker. We observed strongly decreased cerebrospinal fluid amyloid beta(40) (p < 0.01 vs controls or Alzheimer disease) and amyloid beta(42) concentrations (p < 0.001 vs controls and p < 0.05 vs Alzheimer disease) in cerebral amyloid angiopathy patients. The combination of amyloid beta(42) and total tau discriminated cerebral amyloid angiopathy from controls, with an area under the receiver operator curve of 0.98. Our data are consistent with neuropathological evidence that amyloid beta(40) as well as amyloid beta(42) protein are selectively trapped in the cerebral vasculature from interstitial fluid drainage pathways that otherwise transport amyloid beta proteins toward the cerebrospinal fluid.
| S-EPMC3697750 | biostudies-literature