Related Experiment Video
Updated: Oct 23, 2025
The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease
Published on: October 13, 2016
Neuropsychiatric and Cognitive Symptoms Across the Alzheimer Disease Clinical Spectrum: Cross-sectional and
Willem S Eikelboom1, Esther van den Berg1, Ellen H Singleton1
1From the Departments of Neurology (W.S.E., E.v.d.B., J.M.P.), Biostatistics (S.J.B.), and Psychiatry (M.C.), Erasmus MC, University Medical Center, Rotterdam; Department of Neurology, Alzheimer Center Amsterdam (E.H.S., A.E.L., Y.A.L.P., P.S., W.M.v.d.F., R.O.), Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Radiology and Nuclear Medicine (B.N.M.v.B.), Amsterdam University Medical Centers, the Netherlands; and Clinical Memory Research Unit (R.O.), Lund University, Malmö, Sweden.
Background And Objectives:
To investigate the prevalence and trajectories of neuropsychiatric symptoms (NPS) in relation to cognitive functioning in a cohort of β-amyloid-positive (A+) individuals across the Alzheimer disease (AD) clinical spectrum.
Methods:
In this single-center observational study, we included all individuals who visited the Alzheimer Center Amsterdam and had a clinical diagnosis of subjective cognitive decline (SCD), mild cognitive impairment (MCI), or probable AD dementia and were A+. We measured NPS with the Neuropsychiatric Inventory (NPI), examining total scores and the presence of specific NPI domains. Cognition was assessed across 5 cognitive domains and with the Mini-Mental State Examination (MMSE). We examined trajectories including model-based trends for NPS and cognitive functioning over time. We used linear mixed models to relate baseline NPI scores to cognitive functioning at baseline (whole-sample) and longitudinal time points (subsample n = 520, mean 1.8 [SD 0.7] years follow-up).
Results:
We included 1,524 A+ individuals from the Amsterdam Dementia Cohort with A+ SCD (n = 113), A+ MCI (n = 321), or A+ AD dementia (n = 1,090). NPS were prevalent across all clinical AD stages (≥1 NPS 81.4% in SCD, 81.2% in MCI, 88.7% in dementia; ≥1 clinically relevant NPS 54.0% in SCD, 50.5% in MCI, 66.0% in dementia). Cognitive functioning showed a uniform gradual decline; while in contrast, large intraindividual heterogeneity of NPS was observed over time across all AD groups. At baseline, we found associations between NPS and cognition in dementia that were most pronounced for NPI total scores and MMSE (range β = -0.18 to -0.11, false discovery rate [FDR]-adjusted p < 0.05), while there were no cross-sectional relationships in SCD and MCI (range β = -0.32 to 0.36, all FDR-adjusted p > 0.05). There were no associations between baseline NPS and cognitive functioning over time in any clinical stage (range β = -0.13 to 0.44, all FDR-adjusted p > 0.05).
Discussion:
NPS and cognitive symptoms are both prevalent across the AD clinical spectrum, but show a different evolution during the course of the disease.
Related Concept Videos
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:22Alzheimer's Disease: Treatment
01:30Dementia
The progression of dementia is generally gradual....
01:03Long-term Depression
Calcium Ion Concentration Mechanism
If over...
01:30Negative and Cognitive Symptoms of Schizophrenia
Negative Symptoms
Negative symptoms of schizophrenia manifest as deficits in normal emotional and behavioral functioning, profoundly impacting daily life. Individuals with schizophrenia often display a flat affect, characterized by a near-total absence of emotional expression,...
01:30Cognitive Development During Adulthood