TY - JOUR
T1 - Association of Neurogranin and BACE1 With Clinical Cognitive Decline in Individuals With Subjective Cognitive Decline
AU - Wang, Xiao
AU - Freiesleben, Silka D
AU - Schneider, Luisa-Sophie
AU - Preis, Lukas
AU - Priller, Josef
AU - Spruth, Eike J
AU - Altenstein, Slawek
AU - Schneider, Anja
AU - Fliessbach, Klaus
AU - Wiltfang, Jens
AU - Hansen, Niels
AU - Jessen, Frank
AU - Rostamzadeh, Ayda
AU - Duzel, Emrah
AU - Glanz, Wenzel
AU - Incesoy, Enise I
AU - Buerger, Katharina
AU - Janowitz, Daniel
AU - Ewers, Michael
AU - Perneczky, Robert
AU - Rauchmann, Boris-Stephan
AU - Teipel, Stefan J
AU - Kilimann, Ingo
AU - Goerss, Doreen
AU - Laske, Christoph
AU - Munk, Matthias H J
AU - Spottke, Annika
AU - Roy-Kluth, Nina
AU - Heneka, Michael T
AU - Brosseron, Frederic
AU - Wagner, Michael
AU - Wolfsgruber, Steffen
AU - Ramirez, Alfredo
AU - Kleineidam, Luca
AU - Stark, Melina
AU - Peters, Oliver
PY - 2024/10/22
Y1 - 2024/10/22
N2 - BACKGROUND AND OBJECTIVES: CSF biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). However, AD is still diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Thus, further identification of biomarkers is required to detect related pathology in the preclinical stage and predict cognitive decline. Our study aimed to assess the association of neurogranin and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) with cognitive decline in individuals with subjective cognitive decline (SCD).METHODS: We enrolled participants with available neurogranin and BACE1 measurements in CSF from the DELCODE (DZNE-Longitudinal Cognitive Impairment and Dementia, Germany) cohort. The longitudinal change of Preclinical Alzheimer's Cognitive Composite score was assessed as the primary outcome in participants with SCD and controls. The secondary outcome was defined as conversion of SCD to mild cognitive impairment (MCI) during follow-up. Levels of neurogranin, BACE1, and neurogranin/BACE1 ratio across groups were compared by analysis of covariance after adjustment for demographics. The linear mixed-effects model and Cox regression analysis were applied to evaluate their association with cognitive decline and progression of SCD to MCI, respectively.RESULTS: A total of 530 participants (mean age: 70.76 ± 6.01 years, 48.7% female) were analyzed in the study. The rate of cognitive decline was faster in individuals with SCD with higher neurogranin and neurogranin/BACE1 ratio (β = -0.138, SE = 0.065,
p = 0.037, and β = -0.293, SE = 0.115,
p = 0.013). Higher baseline neurogranin and neurogranin/BACE1 ratio were associated with an increased rate of conversion from SCD to MCI (hazard ratio [HR] 1.35 per SD, 95% CI 1.03-1.77,
p = 0.028, and HR 1.53 per SD, 95% CI 1.13-2.07,
p = 0.007). In addition, the impact of higher neurogranin levels on accelerating the rate of cognitive decline was more pronounced in the SCD group than in cognitively unimpaired controls (β = -0.077, SE = 0.033,
p = 0.020).
DISCUSSION: Our findings suggest that CSF neurogranin and BACE1 begin to change in the preclinical stage of AD and they are associated with clinical progression in individuals with SCD.
AB - BACKGROUND AND OBJECTIVES: CSF biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). However, AD is still diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Thus, further identification of biomarkers is required to detect related pathology in the preclinical stage and predict cognitive decline. Our study aimed to assess the association of neurogranin and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) with cognitive decline in individuals with subjective cognitive decline (SCD).METHODS: We enrolled participants with available neurogranin and BACE1 measurements in CSF from the DELCODE (DZNE-Longitudinal Cognitive Impairment and Dementia, Germany) cohort. The longitudinal change of Preclinical Alzheimer's Cognitive Composite score was assessed as the primary outcome in participants with SCD and controls. The secondary outcome was defined as conversion of SCD to mild cognitive impairment (MCI) during follow-up. Levels of neurogranin, BACE1, and neurogranin/BACE1 ratio across groups were compared by analysis of covariance after adjustment for demographics. The linear mixed-effects model and Cox regression analysis were applied to evaluate their association with cognitive decline and progression of SCD to MCI, respectively.RESULTS: A total of 530 participants (mean age: 70.76 ± 6.01 years, 48.7% female) were analyzed in the study. The rate of cognitive decline was faster in individuals with SCD with higher neurogranin and neurogranin/BACE1 ratio (β = -0.138, SE = 0.065,
p = 0.037, and β = -0.293, SE = 0.115,
p = 0.013). Higher baseline neurogranin and neurogranin/BACE1 ratio were associated with an increased rate of conversion from SCD to MCI (hazard ratio [HR] 1.35 per SD, 95% CI 1.03-1.77,
p = 0.028, and HR 1.53 per SD, 95% CI 1.13-2.07,
p = 0.007). In addition, the impact of higher neurogranin levels on accelerating the rate of cognitive decline was more pronounced in the SCD group than in cognitively unimpaired controls (β = -0.077, SE = 0.033,
p = 0.020).
DISCUSSION: Our findings suggest that CSF neurogranin and BACE1 begin to change in the preclinical stage of AD and they are associated with clinical progression in individuals with SCD.
KW - Aged
KW - Aged, 80 and over
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Amyloid Precursor Protein Secretases/cerebrospinal fluid
KW - Aspartic Acid Endopeptidases/cerebrospinal fluid
KW - Biomarkers/cerebrospinal fluid
KW - Cognitive Dysfunction/cerebrospinal fluid
KW - Disease Progression
KW - Longitudinal Studies
KW - Neurogranin/cerebrospinal fluid
U2 - 10.1212/WNL.0000000000209806
DO - 10.1212/WNL.0000000000209806
M3 - Article
C2 - 39303184
SN - 0028-3878
VL - 103
SP - e209806
JO - Neurology
JF - Neurology
IS - 8
ER -