Difference of CSF Biomarkers and Neuropsychiatric Symptoms Profiles Among Normal Cognition, Mild Cognitive Impairment, and Dementia Patient

Abstract

Background: Mild cognitive impairment (MCI) represents a pivotal stage bridging typical aging and dementia, characterized by cognitive impairments encompassing memory, language, reasoning, and judgment. This investigation focuses on individuals with normal cognition, MCI, and dementia, juxtaposing the Neuropsychiatric Inventory Questionnaire (NPI) and cerebrospinal fluid (CSF) biomarkers. The aim is to address gaps in understanding the relationship between neuropsychiatric symptoms and key biomarkers, aiming to identify variations and potential implications for diagnosis and intervention.

Methods: Leveraging data from the National Alzheimer’s Coordinating Center's Uniform Data Set Version 3, this study enrolls a cohort spanning the spectrum from typical cognitive function to MCI or dementia, selectively excluding cases lacking NPI or CSF data or featuring intervals of over three years between CSF testing and NPI assessment. Parameters under scrutiny encompass demographics, lifestyle, physical functioning, comorbidities, medications, NPI scores, and CSF biomarkers.

Results: The study cohort embraces 1,896 participants, including 977 normal cognition, 270 MCI, and 649 dementia individuals. Dementia-affected participants exhibit a male predilection, reduced educational attainment, marital status, cohabitation tendencies, divergent comorbidity incidence, and distinct medication profiles. Dementia is marked by notably elevated NPI scores, primarily attributed to mood-related symptoms (p < 0.001). Median Amyloid-β levels stand at 638.0 pg/mL for normocognition, 309.7 pg/mL for MCI, and 299.1 pg/mL for dementia (p < 0.001). Median P-tau levels for normal cognition, MCI, and dementia cohorts are 36.00, 49.12, and 57.95 pg/mL, respectively (p < 0.001). Median T-tau levels for normal cognition, MCI, and dementia groups are 245.0, 172.6, and 303.6 pg/mL, respectively (p < 0.001).

Conclusion: Among those with normal cognition, MCI, and AD, conspicuous disparities in NPI and CSF biomarkers surface, suggesting that tandem assessment of neuropsychiatric symptoms and pivotal CSF biomarkers may augment early MCI and dementia diagnosis, ameliorating interventions. Ongoing research is requisite to corroborate these findings and scrutinize their potential repercussions for innovative intervention strategies and clinical applications.

Funding: The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD).

Declaration of Interest: No conflicts of interest to declare.

Ethical Approval: The NACC data were de-identified. Researcher using the NACC database was approved by the University of Washington Institutional Review Board. Informed consent was obtained from all participants at the individual ADRC.

Keywords: Mild Cognitive Impairment, Dementia, Alzheimer's Disease, Amyloid-β, P-tau181, T-tau, Cerebrospinal Fluid Biomarker, Neuropsychiatric Inventory Questionnaire