Abstract:
Background: Emerging evidence links Neuropsychiatric Symptoms (NPS) to AD pathogenesis
across the cognitive impairment continuum. However, the role of plasma biomarkers
regarding NPS in preclinical stages is not clear. We examined the relationships between NPS
and p-tau181 and Aβ42 in a sample of Cognitively Unimpaired (CU) and Subjective Cognitive
Decline (SCD) participants.
Methods: A total of 296 participants aged +50 years from the Compostela Ageing Study
(CompAS) recruited from primary care health centers were diagnosed as CU (N=117), and
SCD (N=179) according to Jessen et al. (2014), and defined by cognitive complaints
exceeding age-adjusted cut-off scores in the Questionnaire d’Autoévaluation de la Mémoire
(QAM) (5th percentile, Pereiro et al., 2021). NPS were assessed using the Mild Behavioral
Impairment-Checklist (MBI-C) 12-item (proposed by Mallo et al., 2023; Mallo et al., 2025).
Plasma biomarkers, p-tau181 and Aβ42, were obtained. Group differences were examined
using ANOVA with age, years of schooling, MBI-C 12-item total score and each MBI-C
quadrant score as dependent variables, and clinical diagnosis as factor. Linear regression
analyses (LRA) were performed with MBI-C 12-item total score and scores in each quadrant,
Quadrant-I (Q-I, Resistance), Quadrant-II (Q-II, Restlessness), Quadrant-III (Q-III Desolation),
Quadrant-IV (Q-IV Fattening), as dependent variables; p-tau181 and Aβ42 were predictors.
Results: SCD participants were older and scored higher in Q-II than the CU group (Table 1).
LRA indicated that p-tau181 and Aβ42 were significantly associated with MBI-C 12-item total
score, Q-I, Resistance, and Q-II, Restlessness, considering the total sample. When analyzed
separately, in SCD participants, significant associations were observed only for p-tau181 with
the MBI-C 12-item total score and Q-I and Q-II. In CU participants, significant associations
were found only for Aβ42 with Q-I and Q-II (Table 2).
Conclusion: P-tau181 and Aβ42 were associated with NPS (total score, Q-I and Q-II) across
all participants. However, group-specific patterns emerged: p-tau181 was linked to these
NPS in SCD, while Aβ42 was associated in CU. These findings suggest that tau and amyloid
may differentially link to NPS depending on cognitive status, particularly those related to
Resistance and Restlessness domains.