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Decreased cortical thickness in individuals with subjective cognitive decline with and without CSF‐AD‐pathology: Data from the DELCODE Study
Author(s) -
Meiberth Dix U.,
Hu Xiaochen,
Schild AnnKatrin,
Spottke Annika,
Brosseron Frederic,
Buerger Katharina,
Fließbach Klaus,
Heneka Michael T.,
Kilimann Ingo,
Laske Christoph,
Peters Oliver,
Priller Josef,
Schneider Anja,
Teipel Stefan J.,
Wiltfang Jens,
Wagner Michael,
Düzel Emrah,
Jessen Frank
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044741
Subject(s) - biomarker , entorhinal cortex , cognitive decline , medicine , dementia , cognition , neurodegeneration , psychology , brain aging , disease , oncology , hippocampus , neuroscience , biology , biochemistry
Abstract Background Subjective cognitive decline (SCD) without objective performance deficits reflects in some individuals the earliest symptomatic manifestation of Alzheimer’s Disease (AD) at the late preclinical stage 1,2 . It is crucial to delineate the relationship between SCD, AD‐specific biomarkers and the localization of early neurodegeneration. Method We included the baseline‐dataset of the DELCODE‐study 3 (n=943), from which 404 subjects (57 AD, 89 mild cognitive impairment (MCI), 171 SCD, and 87 healthy controls (CO)) received both CSF‐biomarker‐assessment (Aβ‐42, total‐tau, phosphorylated‐tau) and structural MRI. Cortical thickness was estimated with the FreeSurfer‐Software‐package version 6.0. ANCOVAs with one between‐subject factor of diagnosis, and age, sex, and scanner‐sites as covariates were calculated for the bilateral entorhinal cortices (EC) and bilateral parahippocampi (PH), respectively. Two‐way ANCOVAs with between‐subject factors of diagnosis (SCD/CO) and CSF‐biomarkers (positive/negative) and the same covariates were calculated for each of the regions of interests (ROIs) and CSF‐biomarkers. Result Significant main effects for diagnosis were found for the one‐way‐ANCOVAs for all ROIs (p<0.001; bilateral EC and left PH: HC=SCD>MCI>AD; right PH: HC>SCD>MCI>AD). Two way‐ANCOVA showed significant main effects for diagnosis for the bilateral PH‐thickness (left: p=0.031; right: p=0.013), and an interaction between diagnosis and CSF‐Aß42 for the left PH‐thickness (p=0.022). Post‐hoc analyses showed the interactions were driven by decreased bilateral PH and left EC thickness in SCD subjects compared to CO in the Aβ42 positive subgroups only (p<0.05), not between the Aß42 negative subgroups. Two‐way‐ANCOVA showed also significant interaction effects between the diagnosis and total‐tau, and between the diagnosis and phosphorylated‐tau in the right EC (t‐tau: p=0.011; p‐tau: p=0.004), where SCD subjects had lower right entorhinal thickness than controls in the tau positive subgroups. Conclusion We found decreased bilateral parahippocampal and left entorhinal thickness in persons with SCD compared to controls in all amyloid‐positive cases. In addition, the right entorhinal cortex seems to be affected in SCD compared to controls in all tau positive cases. These data suggest that, in addition to positive AD pathology indicated by CSF biomarkers, the first clinical symptoms such as cognitive complaints may also indicate early degenerative processes in the course of the disease.