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Prediction of Longi...
Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers
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- Mattsson-Carlgren, Niklas (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Brain Injury After Cardiac Arrest,WCMM- Wallenberg center för molekylär medicinsk forskning,Medicinska fakulteten,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,Faculty of Medicine,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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- Salvadó, Gemma (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas
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- Ashton, Nicholas J. (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Stavanger University Hospital,King's College London,South London and Maudsley NHS Foundation Trust
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- Tideman, Pontus (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital
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- Stomrud, Erik (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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- Zetterberg, Henrik, 1973 (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,University College London,Sahlgrenska University Hospital,Hong Kong Center for Neurodegenerative Diseases,Sahlgrenska Academy
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- Ossenkoppele, Rik (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Vrije Universiteit Amsterdam,Amsterdam Neuroscience,Amsterdam UMC - Vrije Universiteit Amsterdam
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- Betthauser, T. J. (författare)
- University of Wisconsin-Madison
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- Cody, K. A. (författare)
- University of Wisconsin-Madison
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- Jonaitis, E. M. (författare)
- University of Wisconsin-Madison
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- Langhough, R. (författare)
- University of Wisconsin-Madison
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- Palmqvist, Sebastian (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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- Blennow, Kaj, 1958 (författare)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska University Hospital,Sahlgrenska Academy
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- Janelidze, Shorena (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas
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- Johnson, S. C. (författare)
- University of Wisconsin-Madison
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- Hansson, Oskar (författare)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital
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(creator_code:org_t)
- 2023-02-06
- 2023
- Engelska.
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149. ; 80:4, s. 360-369
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- IMPORTANCE Alzheimer disease (AD) pathology starts with a prolonged phase of beta-amyloid (A beta) accumulation without symptoms. The duration of this phase differs greatly among individuals. While this disease phase has high relevance for clinical trial designs, it is currently unclear how to best predict the onset of clinical progression.OBJECTIVE To evaluate combinations of different plasma biomarkers for predicting cognitive decline in A beta-positive cognitively unimpaired (CU) individuals.DESIGN, SETTING, AND PARTICIPANTS This prospective population-based prognostic study evaluated data from 2 prospective longitudinal cohort studies (the Swedish BioFINDER-1 and the Wisconsin Registry for Alzheimer Prevention [WRAP]), with data collected from February 8, 2010, to October 21, 2020, for the BioFINDER-1 cohort and from August 11, 2011, to June 27, 2021, for the WRAP cohort. Participants were CU individuals recruited from memory clinics who had brain A beta pathology defined by cerebrospinal fluid (CSF) A beta 42/40 in the BioFINDER-1 study and by Pittsburgh Compound B (PiB) positron emission tomography (PET) in the WRAP study. A total of 564 eligible A beta-positive and A beta-negative CU participants with available relevant data from the BioFINDER-1 and WRAP cohorts were included in the study; of those, 171 A beta-positive participants were included in the main analyses.EXPOSURES Baseline P-tau181, P-tau217, P-tau231, glial fibrillary filament protein, and neurofilament light measured in plasma; CSF biomarkers in the BioFINDER-1 cohort, and PiB PET uptake in the WRAP cohort.MAIN OUTCOMES AND MEASURES The primary outcome was longitudinal measures of cognition (using the Mini-Mental State Examination [MMSE] and the modified Preclinical Alzheimer Cognitive Composite [mPACC]) over a median of 6 years (range, 2-10 years). The secondary outcome was conversion to AD dementia. Baseline biomarkers were used in linear regression models to predict rates of longitudinal cognitive change (calculated separately). Models were adjusted for age, sex, years of education, apolipoprotein E epsilon 4 allele status, and baseline cognition. Multivariable models were compared based on model R-2 coefficients and corrected Akaike information criterion.RESULTS Among 171 A beta-positive CU participants included in the main analyses, 119 (mean [SD] age, 73.0 [5.4] years; 60.5% female) were from the BioFINDER-1 study, and 52 (mean [SD] age, 64.4 [4.6] years; 65.4% female) were from the WRAP study. In the BioFINDER-1 cohort, plasma P-tau217 was the best marker to predict cognitive decline in the mPACC (model R-2 = 0.41) and the MMSE (model R-2 = 0.34) and was superior to the covariates-only models (mPACC: R-2 = 0.23; MMSE: R-2 = 0.04; P < .001 for both comparisons). Results were validated in the WRAP cohort; for example, plasma P-tau217 was associated with mPACC slopes (R-2 = 0.13 vs 0.01 in the covariates-only model; P = .01) and MMSE slopes (R-2 = 0.29 vs 0.24 in the covariates-only model; P = .046). Sparse models were identified with plasma P-tau217 as a predictor of cognitive decline. Power calculations for enrichment in hypothetical clinical trials revealed large relative reductions in sample sizes when using plasma P-tau217 to enrich for CU individuals likely to experience cognitive decline over time.CONCLUSIONS AND RELEVANCE In this study, plasma P-tau217 predicted cognitive decline in patients with preclinical AD. These findings suggest that plasma P-tau217 may be used as a complement to CSF or PET for participant selection in clinical trials of novel disease-modifying treatments.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Neurosciences & Neurology
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Mattsson-Carlgre ...
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Salvadó, Gemma
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Ashton, Nicholas ...
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Tideman, Pontus
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Stomrud, Erik
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Zetterberg, Henr ...
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Ossenkoppele, Ri ...
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Betthauser, T. J ...
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Cody, K. A.
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Jonaitis, E. M.
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Langhough, R.
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Palmqvist, Sebas ...
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Blennow, Kaj, 19 ...
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Janelidze, Shore ...
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Johnson, S. C.
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Hansson, Oskar
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- MEDICIN OCH HÄLSOVETENSKAP
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och Neurovetenskaper
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
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Jama Neurology
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Göteborgs universitet
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