Association of Cerebral Amyloid-beta Aggregation With Cognitive Functioning in Persons Without Dementia
Por:
Jansen, WJ, Ossenkoppele, R, Tijms, BM, Fagan, AM, Hansson, O, Klunk, WE, van der Flier, WM, Villemagne, VL, Frisoni, GB, Fleisher, AS, Lleo, A, Mintun, MA, Wallin, A, Engelborghs, S, Na, DL, Chetelat, G, Molinuevo, JL, Landau, SM, Mattsson, N, Kornhuber, J, Sabri, O, Rowe, CC, Parnetti, L, Popp, J, Fladby, T, Jagust, WJ, Aalten, P, Lee, DY, Vandenberghe, R, de Oliveira, CR, Kapaki, E, Froelich, L, Ivanoiu, A, Gabryelewicz, T, Verbeek, MM, Sanchez-Juan, P, Hildebrandt, H, Camus, V, Zboch, M, Brooks, DJ, Drzezga, A, Rinne, JO, Newberg, A, de Mendonca, A, Sarazin, M, Rabinovici, GD, Madsen, K, Kramberger, MG, Nordberg, A, Mok, V, Mroczko, B, Wolk, DA, Meyer, PT, Tsolaki, M, Scheltens, P, Verhey, FRJ, Visser, PJ, Amyloid Biomarker Study Grp
Publicada:
1 ene 2018
Resumen:
IMPORTANCE Cerebral amyloid-beta aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.
OBJECTIVE To investigate whether amyloid-beta aggregation is associated with cognitive functioning in persons without dementia.
DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.
MAIN OUTCOMES AND MEASURES Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score <= 27 or memory z score <=-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.
RESULTS Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4%[95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3%[95% CI, -1% to 6%], P =.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16%[95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14%[95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.
CONCLUSIONS AND RELEVANCE Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
Filiaciones:
Jansen, WJ:
Maastricht Univ, Alzheimer Ctr Limburg, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, POB 616, NL-6200MD Maastricht, Netherlands
Ossenkoppele, R:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neuroscience Campus, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neuroscience Campus, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Radiol & Nucl Med, Neurosci Campus, Amsterdam, Netherlands
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA USA
Tijms, BM:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neuroscience Campus, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neuroscience Campus, Amsterdam, Netherlands
Fagan, AM:
Washington Univ, Sch Med, Dept Neurol, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA
Hansson, O:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Klunk, WE:
Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA
van der Flier, WM:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neuroscience Campus, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neuroscience Campus, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands
Villemagne, VL:
Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia
Austin Hlth, Ctr PET, Melbourne, Vic, Australia
Frisoni, GB:
Ctr San Giovanni Dio Fatebenefratelli, IRCCS, Lab Alzheimers Neuroimaging & Epidemiol, Brescia, Italy
Univ Hosp, Memory Clin, Geneva, Switzerland
Univ Hosp, LANVIE Lab Neuroimaging Aging, Geneva, Switzerland
Univ Geneva, Geneva, Switzerland
Fleisher, AS:
Banner Alzheimers Inst, Phoenix, AZ USA
Eli Lilly & Co, Indianapolis, IN 46285 USA
Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA
Lleo, A:
Hosp Sant Pau, Neurol Dept, Barcelona, Spain
Mintun, MA:
Avid Radiopharmaceut, Philadelphia, PA USA
Wallin, A:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Molndal, Sweden
Engelborghs, S:
Univ Antwerp, Reference Ctr Biol Markers Dementia BIODEM, Antwerp, Belgium
Na, DL:
Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Neurol, Seoul, South Korea
Chetelat, G:
CHU Caen, INSERM, Caen, France
Molinuevo, JL:
Clin Univ Hosp, Alzheimers Dis & Other Cognit Disorders Unit, IDIBAPS, Barcelona, Spain
Landau, SM:
Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
Mattsson, N:
Lund Univ, Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Kornhuber, J:
Friedrich Alexander Univ Erlangen Nuremberg, Dept Psychiat & Psychotherapy, Erlangen, Germany
Sabri, O:
Univ Leipzig, Dept Nucl Med, Leipzig, Germany
Rowe, CC:
Washington Univ, Sch Med, Dept Neurol, Knight Alzheimers Dis Res Ctr, St Louis, MO 63110 USA
Austin Hlth, Dept Nucl Med, Melbourne, Vic, Australia
Austin Hlth, Ctr PET, Melbourne, Vic, Australia
Parnetti, L:
Univ Perugia, Ctr Memory Disturbances, Sect Neurol, Perugia, Italy
Popp, J:
Univ Hosp Lausanne, Dept Psychiat, Serv Old Age Psychiat, Lausanne, Switzerland
Fladby, T:
Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway
Jagust, WJ:
Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
Aalten, P:
Maastricht Univ, Alzheimer Ctr Limburg, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, POB 616, NL-6200MD Maastricht, Netherlands
Lee, DY:
Seoul Natl Univ, Coll Med, Dept Neuropsychiat, Seoul, South Korea
Vandenberghe, R:
Katholieke Univ Leuven, Lab Cognit Neurol, Leuven, Belgium
Katholieke Univ Leuven, Alzheimer Res Ctr, KU Leuven, Leuven, Belgium
de Oliveira, CR:
Ctr Hosp, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal
Univ Coimbra, Coimbra, Portugal
Kapaki, E:
Natl & Kapodistrian Univ Athens, Eginit Hosp, Med Sch, Dept Neurol 1, Athens, Greece
Froelich, L:
Heidelberg Univ, Dept Geriatr Psychiat, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany
Ivanoiu, A:
Catholic Univ Louvain, Inst Neurosci, Memory Clin, St Luc Univ Hosp, Brussels, Belgium
Catholic Univ Louvain, Inst Neurosci, Neurochem Lab, St Luc Univ Hosp, Brussels, Belgium
Gabryelewicz, T:
Polish Acad Sci, Mossakowski Med Res Ctr, Dept Neurodegenerat Disorders, Warsaw, Poland
Verbeek, MM:
Maastricht Univ, Alzheimer Ctr Limburg, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, POB 616, NL-6200MD Maastricht, Netherlands
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol,Radboud Alzheimer Ctr, Nijmegen, Netherlands
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Radboud Alzheimer Ctr,Lab Med, Nijmegen, Netherlands
Sanchez-Juan, P:
Univ Hosp Marques De Valdecilla, IDIVAL, Neurol Serv, Santander, Spain
Hildebrandt, H:
Hosp Bremen Ost, Ctr Neurol, Bremen, Germany
Camus, V:
CHRU Tours, CIC INSERM 1415, U930, Tours, France
Univ Francois Rabelais Tours, Tours, France
Zboch, M:
Wroclaw Med Univ, Alzheimer Ctr, Scinawa, Poland
Brooks, DJ:
Imperial Coll London, Div Neurosci, Med Res Council Clin Sci Ctr, London, England
Drzezga, A:
Univ Cologne, Dept Nucl Med, Cologne, Germany
Rinne, JO:
Univ Turku, Turku PET Ctr, Turku, Finland
Univ Turku, Div Neurosci Turku, Turku, Finland
Turku Univ Hosp, Turku, Finland
Newberg, A:
Thomas Jefferson Univ & Hosp, Myrna Brind Ctr Integrat Med, Philadelphia, PA USA
de Mendonca, A:
Univ Lisbon, Inst Mol Med, Lisbon, Portugal
Univ Lisbon, Fac Med, Lisbon, Portugal
Sarazin, M:
Univ Paris 05, Ctr Hosp St Anne, Neurol Memoire & Langage, Paris, France
Rabinovici, GD:
Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA
Madsen, K:
Copenhagen Univ Hosp, Neurobiol Res Unit, Copenhagen, Denmark
Kramberger, MG:
Univ Med Ctr Ljubljana, Ctr Cognit Impairments, Ljubljana, Slovenia
Nordberg, A:
Karolinska Univ Hosp, Translat Alzheimer Neurobiol, Ctr Alzheimer Res, Karolinska Inst,Dept NVS, Stockholm, Sweden
Karolinska Univ Hosp, Geriatr Med, Stockholm, Sweden
Mok, V:
Therese Pei Fong Chow Res Ctr Prevent Dementia, Lui Che Woo Inst Innovat Med, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China
Mroczko, B:
Med Univ Bialystok, Dept Neurodegenerat Diagnost, Leading Natl Res Ctr Bialystok KNOW, Bialystok, Poland
Wolk, DA:
Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA
Meyer, PT:
Univ Hosp Freiburg, Dept Nucl Med, Freiburg, Germany
Tsolaki, M:
Aristotle Univ Thessaloniki, Dept Neurol 3, Thessaloniki, Greece
Scheltens, P:
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neuroscience Campus, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neuroscience Campus, Amsterdam, Netherlands
Visser, PJ:
Maastricht Univ, Alzheimer Ctr Limburg, Dept Psychiat & Neuropsychol, Sch Mental Hlth & Neurosci, POB 616, NL-6200MD Maastricht, Netherlands
Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Neuroscience Campus, Amsterdam, Netherlands
Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neuroscience Campus, Amsterdam, Netherlands
Green Published, Bronze, Green Accepted
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