TY - JOUR
T1 - Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia
AU - Jansen, Willemijn J
AU - Ossenkoppele, Rik
AU - Tijms, Betty M
AU - Fagan, Anne M
AU - Hansson, Oskar
AU - Klunk, William E
AU - van der Flier, Wiesje M
AU - Villemagne, Victor L
AU - Frisoni, Giovanni B
AU - Fleisher, Adam S
AU - Lleó, Alberto
AU - Mintun, Mark A
AU - Wallin, Anders
AU - Engelborghs, Sebastiaan
AU - Na, Duk L
AU - Chételat, Gäel
AU - Molinuevo, José Luis
AU - Landau, Susan M
AU - Mattsson, Niklas
AU - Kornhuber, Johannes
AU - Sabri, Osama
AU - Rowe, Christopher C
AU - Parnetti, Lucilla
AU - Popp, Julius
AU - Fladby, Tormod
AU - Jagust, William J
AU - Aalten, Pauline
AU - Lee, Dong Young
AU - Vandenberghe, Rik
AU - Resende de Oliveira, Catarina
AU - Kapaki, Elisabeth
AU - Froelich, Lutz
AU - Ivanoiu, Adrian
AU - Gabryelewicz, Tomasz
AU - Verbeek, Marcel M
AU - Sanchez-Juan, Páscual
AU - Hildebrandt, Helmut
AU - Camus, Vincent
AU - Zboch, Marzena
AU - Brooks, David J
AU - Drzezga, Alexander
AU - Rinne, Juha O
AU - Newberg, Andrew
AU - de Mendonça, Alexandre
AU - Sarazin, Marie
AU - Rabinovici, Gil D
AU - Madsen, Karine
AU - Frederiksen, Kristian S
AU - Johannsen, Peter
AU - Waldemar, Gunhild
AU - Amyloid Biomarker Study Group
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Importance: Cerebral amyloid-β 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-β 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.
AB - Importance: Cerebral amyloid-β 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-β 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.
KW - Journal Article
U2 - 10.1001/jamapsychiatry.2017.3391
DO - 10.1001/jamapsychiatry.2017.3391
M3 - Journal article
C2 - 29188296
SN - 2168-622X
SP - 84
EP - 95
JO - JAMA Psychiatry
JF - JAMA Psychiatry
ER -