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000256452 037__ $$aDZNE-2023-00314
000256452 041__ $$aEnglish
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000256452 1001_ $$0P:(DE-2719)9000823$$aYildirim, Zerrin$$b0$$udzne
000256452 245__ $$aBrain reserve contributes to distinguishing preclinical Alzheimer's stages 1 and 2.
000256452 260__ $$aLondon$$bBioMed Central$$c2023
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000256452 520__ $$aIn preclinical Alzheimer's disease, it is unclear why some individuals with amyloid pathologic change are asymptomatic (stage 1), whereas others experience subjective cognitive decline (SCD, stage 2). Here, we examined the association of stage 1 vs. stage 2 with structural brain reserve in memory-related brain regions.We tested whether the volumes of hippocampal subfields and parahippocampal regions were larger in individuals at stage 1 compared to asymptomatic amyloid-negative older adults (healthy controls, HCs). We also tested whether individuals with stage 2 would show the opposite pattern, namely smaller brain volumes than in amyloid-negative individuals with SCD. Participants with cerebrospinal fluid (CSF) biomarker data and bilateral volumetric MRI data from the observational, multi-centric DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study were included. The sample comprised 95 amyloid-negative and 26 amyloid-positive asymptomatic participants as well as 104 amyloid-negative and 47 amyloid-positive individuals with SCD. Volumes were based on high-resolution T2-weighted images and automatic segmentation with manual correction according to a recently established high-resolution segmentation protocol.In asymptomatic individuals, brain volumes of hippocampal subfields and of the parahippocampal cortex were numerically larger in stage 1 compared to HCs, whereas the opposite was the case in individuals with SCD. MANOVAs with volumes as dependent data and age, sex, years of education, and DELCODE site as covariates showed a significant interaction between diagnosis (asymptomatic versus SCD) and amyloid status (Aß42/40 negative versus positive) for hippocampal subfields. Post hoc paired comparisons taking into account the same covariates showed that dentate gyrus and CA1 volumes in SCD were significantly smaller in amyloid-positive than negative individuals. In contrast, CA1 volumes were significantly (p = 0.014) larger in stage 1 compared with HCs.These data indicate that HCs and stages 1 and 2 do not correspond to linear brain volume reduction. Instead, stage 1 is associated with larger than expected volumes of hippocampal subfields in the face of amyloid pathology. This indicates a brain reserve mechanism in stage 1 that enables individuals with amyloid pathologic change to be cognitively normal and asymptomatic without subjective cognitive decline.
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000256452 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x1
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000256452 650_7 $$2Other$$aAlzheimer’s disease (AD)
000256452 650_7 $$2Other$$aAmyloid pathologic change
000256452 650_7 $$2Other$$aAß42/40
000256452 650_7 $$2Other$$aBrain reserve
000256452 650_7 $$2Other$$aCerebrospinal fluid (CSF)
000256452 650_7 $$2Other$$aHippocampus
000256452 650_7 $$2Other$$aMagnetic resonance imaging (MRI)
000256452 650_7 $$2Other$$aMedial temporal lobe
000256452 650_7 $$2Other$$aMemory
000256452 650_7 $$2Other$$aSubjective cognitive decline (SCD)
000256452 650_7 $$2NLM Chemicals$$aAmyloidogenic Proteins
000256452 650_2 $$2MeSH$$aHumans
000256452 650_2 $$2MeSH$$aAged
000256452 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000256452 650_2 $$2MeSH$$aCognitive Reserve
000256452 650_2 $$2MeSH$$aAmyloidogenic Proteins
000256452 650_2 $$2MeSH$$aCerebral Cortex
000256452 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000256452 693__ $$0EXP:(DE-2719)DELCODE-20140101$$5EXP:(DE-2719)DELCODE-20140101$$eLongitudinal Cognitive Impairment and Dementia Study$$x0
000256452 7001_ $$aDelen, Firuze$$b1
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000256452 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b15$$udzne
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000256452 7001_ $$0P:(DE-2719)2810593$$aBrosseron, Frederic$$b29$$udzne
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000256452 7001_ $$0P:(DE-2719)2810395$$aRoeske, Sandra$$b31$$udzne
000256452 7001_ $$0P:(DE-2719)2812825$$aRamirez, Alfredo$$b32$$udzne
000256452 7001_ $$0P:(DE-2719)9000543$$aEwers, Michael$$b33$$udzne
000256452 7001_ $$aDechent, Peter$$b34
000256452 7001_ $$aHetzer, Stefan$$b35
000256452 7001_ $$aScheffler, Klaus$$b36
000256452 7001_ $$0P:(DE-2719)2812139$$aKleineidam, Luca$$b37$$udzne
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