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000283068 0247_ $$2ISSN$$a1552-5279
000283068 037__ $$aDZNE-2025-01475
000283068 041__ $$aEnglish
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000283068 1001_ $$0P:(DE-2719)9001773$$aStark, Melina$$b0$$eFirst author$$udzne
000283068 1112_ $$aAlzheimer’s Association International Conference$$cToronto$$d2025-07-27 - 2025-07-31$$gAAIC 25$$wCanada
000283068 245__ $$aSubjective Cognitive Decline and Minor Neuropsychological Deficits: Importance for Risk Stratification and Trial Recruitment in Early Alzheimer´s Disease
000283068 260__ $$c2025
000283068 3367_ $$0PUB:(DE-HGF)1$$2PUB:(DE-HGF)$$aAbstract$$babstract$$mabstract$$s1767013827_31206
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000283068 520__ $$aThe recruitment of participants with a high risk of decline is crucial for the success of clinical trials in the earliest phases of Alzheimer´s Disease (AD), where treatment benefits could be the largest. Subjective cognitive decline (SCD) and minor neuropsychological deficits (MNPD) are associated with an increased risk of cognitive decline, making them promising predictors for this risk stratification. However, the prognostic value of their interplay is understudied.We pooled and analyzed data from cognitively unimpaired participants from the Alzheimer´s Disease Neuroimaging Initiative (N = 599), DZNE Longitudinal Cognitive Impairment and Dementia study (N = 618), and National Alzheimer's Coordinating Center (N = 11,975). SCD was measured using questionnaires or anamnestic data. MNPD was defined as a median neuropsychological test performance of z≤-0.5. We assessed the association of MNPD and SCD with the conversion to mild cognitive impairment (MCI) and dementia (cox regression) and baseline amyloid and tau positivity - measured by PET/CSF (logistic regression). We adjusted these models for the study cohorts and demographic covariates. Using power analyses, we calculated the sample sizes necessary to detect a 30% reduction in the risk of progressing to MCI over 4.5 years in amyloid positive participants.In the overall sample (N = 13,192), the SCD-/MNPD+ (+:present, -:absent; HR=3.13[2.68-3.66]), SCD+/MNPD- (HR=1.97[1.76-2.20]), and SCD+/MNPD+ (HR=6.23[5.23-7.42]) groups had an increased risk of MCI compared to the SCD-/MNPD- group. These groups also had an increased risk of dementia. In amyloid positive participants (n = 497), this pattern persisted for the progression to MCI, while only the SCD+/MNPD+ group had an increased risk for dementia. In participants with biomarker data (n = 2,616), the SCD+/MNPD- (OR=1.47[1.20-1.81]) and SCD+/MNPD+ (OR=1.64[1.04-2.59]) groups had an increased risk of amyloid positivity. The risk of tau positivity was increased in the SCD+/MNPD+ group (OR=2.10[1.13-3.90]). In the power analyses, the required clinical trial size was reduced by approximately one third after excluding SCD-/MNPD- individuals and approximately two thirds by focusing only on SCD+/MNPD+ individuals (Figure).SCD and MNPD have a complementary prognostic value. SCD+/MNPD+ individuals are at particularly high risk of pathology and decline. These clinical symptoms should be taken into account in the recruitment for clinical trials in preclinical AD.
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000283068 650_7 $$2NLM Chemicals$$atau Proteins
000283068 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000283068 650_7 $$2NLM Chemicals$$aBiomarkers
000283068 650_2 $$2MeSH$$aHumans
000283068 650_2 $$2MeSH$$aMale
000283068 650_2 $$2MeSH$$aFemale
000283068 650_2 $$2MeSH$$aAged
000283068 650_2 $$2MeSH$$aCognitive Dysfunction: diagnosis
000283068 650_2 $$2MeSH$$aCognitive Dysfunction: diagnostic imaging
000283068 650_2 $$2MeSH$$aCognitive Dysfunction: cerebrospinal fluid
000283068 650_2 $$2MeSH$$aCognitive Dysfunction: psychology
000283068 650_2 $$2MeSH$$aNeuropsychological Tests
000283068 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000283068 650_2 $$2MeSH$$aAlzheimer Disease: diagnosis
000283068 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000283068 650_2 $$2MeSH$$aAlzheimer Disease: psychology
000283068 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000283068 650_2 $$2MeSH$$aDisease Progression
000283068 650_2 $$2MeSH$$aLongitudinal Studies
000283068 650_2 $$2MeSH$$aAged, 80 and over
000283068 650_2 $$2MeSH$$aPositron-Emission Tomography
000283068 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000283068 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000283068 7001_ $$0P:(DE-2719)9002169$$aKuhn, Elizabeth$$b1$$udzne
000283068 7001_ $$0P:(DE-2719)2000057$$aWagner, Michael$$b2$$udzne
000283068 7001_ $$0P:(DE-2719)2810726$$aBoecker, Henning$$b3$$udzne
000283068 7001_ $$0P:(DE-2719)2810593$$aBrosseron, Frederic$$b4$$udzne
000283068 7001_ $$0P:(DE-2719)2811351$$aBuerger, Katharina$$b5$$udzne
000283068 7001_ $$0P:(DE-2719)2811028$$aDaamen, Marcel$$b6$$udzne
000283068 7001_ $$0P:(DE-2719)2000055$$aLaske, Christoph$$b7$$udzne
000283068 7001_ $$0P:(DE-2719)2812234$$aPerneczky, Robert$$b8$$udzne
000283068 7001_ $$0P:(DE-2719)2811024$$aPeters, Oliver$$b9$$udzne
000283068 7001_ $$0P:(DE-2719)2811122$$aPriller, Josef$$b10$$udzne
000283068 7001_ $$0P:(DE-2719)2811245$$aSchmid, Matthias$$b11$$udzne
000283068 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b12$$udzne
000283068 7001_ $$0P:(DE-2719)2811324$$aSpottke, Annika$$b13$$udzne
000283068 7001_ $$0P:(DE-2719)2000026$$aTeipel, Stefan J$$b14$$udzne
000283068 7001_ $$0P:(DE-2719)2811317$$aWiltfang, Jens$$b15$$udzne
000283068 7001_ $$0P:(DE-2719)2000005$$aDüzel, Emrah$$b16$$udzne
000283068 7001_ $$0P:(DE-2719)2000032$$aJessen, Frank$$b17$$udzne
000283068 7001_ $$0P:(DE-2719)2812139$$aKleineidam, Luca$$b18$$eLast author$$udzne
000283068 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz70857_102815$$gVol. 21 Suppl 3, no. Suppl 3, p. e102815$$nSuppl 3$$pe102815$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025
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