Age and diagnostic performance of Alzheimer disease CSF biomarkers

Mattsson, Niklas; Rosen, Eric; Hansson, Oskar; Andreasen, Niels; Parnetti, Lucilla; Jonsson, Michael; Herukka, Sanna Kaisa; Flier, Wiesje M. van der; Blankenstein, Marinus A.; Ewers, Michael; Rich, Kenneth; Kaiser, Elmar; Verbeek, Marcel M.; Rikkert, Marcel G M Olde; Tsolaki, Magda; Mulugeta, Ezra; Aarsland, Dag; Visser, Pieter Jelle; Schröder, Johannes; Marcusson, Jan; Leon, Mony J. de; Hampel, Harald; Scheltens, Philip; Wallin, Anders; Eriksdotter, Maria; Minthon, Lennart; Winblad, Bengt; Blennow, Kaj; Zetterberg, Henrik

doi:10.1212/wnl.0b013e3182477eed

Cited by 156 publications

(127 citation statements)

References 42 publications

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“…14,16 Age-related changes also occur with other markers of MCI and AD dementia: cognitive test performance, MRI atrophy indices, FDG (2-deoxy-2-[ b-amyloid 42 with increased tau and phospho-tau in CSF. [31][32][33][34] Also, odor identification deficits have limited specificity because they occur in nonspecific anosmia, Parkinson disease, schizophrenia, and alcoholism. 16,35,36 These disorders need to be excluded before olfactory testing is used as a predictor of cognitive decline or transition to AD.…”

Section: Baseline Demographic and Clinical Measuresmentioning

confidence: 99%

Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community

et al. 2015

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Objective: To determine the predictive utility of baseline odor identification deficits for future cognitive decline and the diagnosis of Alzheimer disease (AD) dementia.Methods: In a multiethnic community cohort in North Manhattan, NY, 1,037 participants without dementia were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). In 757 participants, follow-up occurred at 2 years and 4 years.Results: In logistic regression analyses, lower baseline UPSIT scores were associated with cognitive decline (relative risk 1.067 per point interval; 95% confidence interval [CI] 1.040, 1.095; p , 0.0001), and remained significant (relative risk 1.065 per point interval; 95% CI 1.034, 1.095; p , 0.0001) after including covariates. UPSIT, but not Selective Reminding Test-total immediate recall, predicted cognitive decline in participants without baseline cognitive impairment. During follow-up, 101 participants transitioned to AD dementia. In discrete time survival analyses, lower baseline UPSIT scores were associated with transition to AD dementia (hazard ratio 1.099 per point interval; 95% CI 1.067, 1.131; p , 0.0001), and remained highly significant (hazard ratio 1.072 per point interval; 95% CI 1.036, 1.109; p , 0.0001) after including demographic, cognitive, and functional covariates.Conclusions: Impairment in odor identification was superior to deficits in verbal episodic memory in predicting cognitive decline in cognitively intact participants. The findings support the crosscultural use of a relatively inexpensive odor identification test as an early biomarker of cognitive decline and AD dementia. Such testing may have the potential to select/stratify patients in treatment trials of cognitively impaired patients or prevention trials in cognitively intact individuals.Neurology ® 2015;84:182-189 GLOSSARY AD 5 Alzheimer disease; AUC 5 area under the curve; CI 5 confidence interval; HR 5 hazard ratio; MCI 5 mild cognitive impairment; ROC 5 receiver operating characteristic; RR 5 relative risk; SRT 5 Selective Reminding Test; SRT-TR 5 Selective Reminding Test-total immediate recall; UPSIT 5 University of Pennsylvania Smell Identification Test; WHICAP 5 Washington Heights/Inwood Columbia Aging Project.

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Section: Baseline Demographic and Clinical Measuresmentioning

confidence: 99%

Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community

et al. 2015

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“…Several studies have evaluated the usefulness of cerebrospinal fluid (CSF) total tau and phospho-tau levels in patients with FTLD, but with contrasting findings [4][5][6][7][8]. Indeed, while it has been widely demonstrated that CSF tau, phospho-tau, and amyloid-␤ (A␤) markers are reliable tools to identify Alzheimer's disease in the preclinical stages [9][10][11], in FTLD, the results have been highly variable. Some studies have shown statistically increase of CSF tau, whereas others have shown unremarkable levels [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Tau in Frontotemporal Lobar Degeneration: Clinical, Neuroimaging, and Prognostic Correlates

Borroni

Cerini

Archetti

et al. 2011

JAD

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Abstract. Frontotemporal lobar degeneration (FTLD) refers to heterogeneous clinical and biological conditions. In FTLD, cerebrospinal fluid (CSF) tau levels have been reported highly variable. The aim of the present study was to evaluate whether CSF tau might be the hallmark of a distinct FTLD phenotype. Fifty-five FTLD patients, who underwent CSF analysis, were considered in the present study. In each patient, a wide standardized neuropsychological evaluation, and CSF tau, phospho-tau, and amyloid-␤ (A␤) dosages were performed. Each patient was followed-up to five years, and outcomes carefully recorded. In a subgroup of patients (n = 24), magnetic resonance imaging scanning was performed, by using voxel-based morphometry, for grey matter investigation. The higher the CSF tau levels, the worse the neuropsychological and neuroimaging pattern, mainly characterized by greater language disturbances and left temporal grey matter loss. The same pattern, even if less significant, was associated with CSF phospho-tau, while CSF A␤ levels did not play any influence on FTLD phenotype. FTLD patients with high CSF tau showed poor prognosis compared to those with low CSF tau (p = 0.031). In FTLD, CSF tau levels might be considered a marker of neurodegeneration, associated with a specific clinical and neuroimaging picture, and significantly related to poor outcome. Further studies aimed at defining the biological underpinnings of these findings are warranted.

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“…For example, AD is characterized by decreased CSF concentrations of Aβ 42 and increased concentrations of tau. Investigating the prevalence and prognostic value of CSF biomarkers in patients with mild/subjective cognitive impairment will be crucial in the near future to decide whether CSF analysis is to become routine in people with memory complaints for the diagnosis of disorders such as AD [55,56,57]. …”

Section: Discussionmentioning

confidence: 99%

The Uniqueness of Biobanks for Neurological and Psychiatric Diseases: Potentials and Pitfalls

Ravid¹

2014

Pathobiology

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Objectives: Central nervous system (CNS) biobanks are facing difficult and specific challenges due to the sensitive issue of collecting specimens of the CNS, and especially the brain. At present, there is no global network/central database to serve researchers, clinicians and pharma companies, or to supply the special specimens and the accompanying data in sufficient numbers and detail, respectively. The main challenge/objective is to standardize and harmonize all the facets involved in CNS biobanking in order to maximize efficient sample collection. Methods: Since the number of CNS biospecimens stored in existing biobanks is relatively limited and the accompanying data are not always readily available and hard to identify, we propose using optimal procedures for handling and storage of these specimens, and the global standardization of the cliniconeuropathological diagnostic criteria. Results: One of the prominent achievements of the current global activity in brain tissue biobanks (BTB-banks) is the development of an inventory of international standards, available specimens and concomitant data, and national registries. Conclusions: Taking into consideration the huge variety of the specimens stored in different repositories and the enormous differences in medicolegal systems and ethics regulations in different countries, we strongly recommend that healthcare systems and institutions who host BTB-banks make efforts to secure adequate funding for the infrastructure and daily activities. BTB-banks will refine standard operating procedures and their internal guides of best practices/codes of conduct. This in turn will enable the BTB-banks to share the collected specimens and data with the largest possible number of researchers, aiming at maximal scientific spin-off and advance of public health research.

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Age and diagnostic performance of Alzheimer disease CSF biomarkers

Abstract: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations.

Cited by 156 publications

References 42 publications

Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community

Olfactory deficits predict cognitive decline and Alzheimer dementia in an urban community

Cerebrospinal Fluid Tau in Frontotemporal Lobar Degeneration: Clinical, Neuroimaging, and Prognostic Correlates

The Uniqueness of Biobanks for Neurological and Psychiatric Diseases: Potentials and Pitfalls

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