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@INPROCEEDINGS{Stark:283068,
      author       = {Stark, Melina and Kuhn, Elizabeth and Wagner, Michael and
                      Boecker, Henning and Brosseron, Frederic and Buerger,
                      Katharina and Daamen, Marcel and Laske, Christoph and
                      Perneczky, Robert and Peters, Oliver and Priller, Josef and
                      Schmid, Matthias and Schneider, Anja and Spottke, Annika and
                      Teipel, Stefan J and Wiltfang, Jens and Düzel, Emrah and
                      Jessen, Frank and Kleineidam, Luca},
      title        = {{S}ubjective {C}ognitive {D}ecline and {M}inor
                      {N}europsychological {D}eficits: {I}mportance for {R}isk
                      {S}tratification and {T}rial {R}ecruitment in {E}arly
                      {A}lzheimer´s {D}isease},
      journal      = {Alzheimer's and dementia},
      volume       = {21},
      number       = {Suppl 3},
      issn         = {1552-5260},
      reportid     = {DZNE-2025-01475},
      pages        = {e102815},
      year         = {2025},
      abstract     = {The 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.},
      month         = {Jul},
      date          = {2025-07-27},
      organization  = {Alzheimer’s Association
                       International Conference, Toronto
                       (Canada), 27 Jul 2025 - 31 Jul 2025},
      keywords     = {Humans / Male / Female / Aged / Cognitive Dysfunction:
                      diagnosis / Cognitive Dysfunction: diagnostic imaging /
                      Cognitive Dysfunction: cerebrospinal fluid / Cognitive
                      Dysfunction: psychology / Neuropsychological Tests /
                      Alzheimer Disease: diagnostic imaging / Alzheimer Disease:
                      diagnosis / Alzheimer Disease: cerebrospinal fluid /
                      Alzheimer Disease: psychology / tau Proteins: cerebrospinal
                      fluid / Disease Progression / Longitudinal Studies / Aged,
                      80 and over / Positron-Emission Tomography / Amyloid
                      beta-Peptides: cerebrospinal fluid / Biomarkers:
                      cerebrospinal fluid / tau Proteins (NLM Chemicals) / Amyloid
                      beta-Peptides (NLM Chemicals) / Biomarkers (NLM Chemicals)},
      cin          = {AG Wagner / AG Boecker / AG Heneka / Clinical Research
                      (Munich) / AG Gasser / AG Dichgans / AG Peters / AG Priller
                      / AG Schmid Bonn / AG Schneider / AG Spottke / AG Teipel /
                      AG Wiltfang / AG Düzel / AG Jessen},
      ddc          = {610},
      cid          = {I:(DE-2719)1011201 / I:(DE-2719)1011202 /
                      I:(DE-2719)1011303 / I:(DE-2719)1111015 / I:(DE-2719)1210000
                      / I:(DE-2719)5000022 / I:(DE-2719)5000000 /
                      I:(DE-2719)5000007 / I:(DE-2719)1013028 / I:(DE-2719)1011305
                      / I:(DE-2719)1011103 / I:(DE-2719)1510100 /
                      I:(DE-2719)1410006 / I:(DE-2719)5000006 /
                      I:(DE-2719)1011102},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
      pubmed       = {pmid:41447391},
      pmc          = {pmc:PMC12740029},
      doi          = {10.1002/alz70857_102815},
      url          = {https://pub.dzne.de/record/283068},
}