Multimodal Biomarkers in Individual With Cognitive Impairment and Dementia

Multimodal Biomarkers in Individual With Cognitive Impairment and Dementia: A Case Control Study

Memory problems can range from normal aging to mild cognitive impairment (MCI) to dementia. This study looks at three ways of measuring what is happening in the brain at each of these stages: a blood test (GFAP), a brain MRI scan, and a brain wave test (EEG). The goal is to see whether combining these three tests can help doctors tell the difference between normal aging, MCI, and dementia more accurately, and whether this approach works well in an Egyptian population, including all common causes of dementia (not only Alzheimer's disease).

Adults aged 50 to 85 will be placed into one of three groups: those with normal memory, those with mild memory problems (MCI), and those with dementia. Everyone will have a memory and thinking assessment, a blood draw, a brain MRI, and a brain wave (EEG) recording. No new medication or treatment is given as part of this study; it involves only assessment and testing. The information gathered may help doctors diagnose memory problems earlier and more accurately in the future.

Study Overview

• Status: Not yet recruiting
• Conditions: Mild Cognitive Impairment (MCI); Dementia Disorders

Detailed Description

This is a cross-sectional, observational, case-control study designed to characterize and compare plasma glial fibrillary acidic protein (GFAP), quantitative electroencephalography (EEG), and MRI-based brain volumetry across three groups: healthy controls, participants with mild cognitive impairment (MCI), and participants with dementia of any etiology (Alzheimer's, vascular, Lewy body, frontotemporal, or mixed).

Plasma GFAP, an astrocytic activation marker, will be quantified from EDTA-collected blood via automated chemiluminescent immunoassay (Lumipulse or Alinity platform where available) or conventional ELISA. Structural brain volumetry (hippocampal, medial temporal, and whole-brain/ventricular volumes) will be derived from 3-Tesla MRI using a 3D T1-weighted MPRAGE sequence with automated segmentation. Resting-state EEG will be recorded using a 19-channel 10-20 electrode montage for quantitative spectral power analysis across standard frequency bands.

All participants will undergo a standardized clinical and psychometric assessment, including the Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating (CDR), and functional assessment via the Katz Index and Lawton-Brody Instrumental Activities of Daily Living scale, to confirm group classification prior to biomarker collection.

The study addresses a gap in the literature: although plasma GFAP, MRI volumetry, and EEG have each been separately validated as markers of neurodegeneration, few studies have jointly acquired all three modalities within a single cohort spanning the full continuum from normal cognition through dementia, and fewer still have done so in an Egyptian or broader Middle East/North Africa population across all dementia etiologies rather than Alzheimer's disease alone. Findings from this study are intended to inform the development of a combined biomarker panel for earlier and more accurate differentiation between normal cognitive aging, MCI, and dementia.

• Study Type: Observational
• Enrollment (Estimated): 75

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

The study will include three groups matched for age, sex and educational level: from Outpatient clinic of the Department of Neurology and Psychiatry, Assiut University Hospitals healthy controls, patients with mild cognitive impairment (MCI), and patients with dementia of any etiology (Alzheimer's, vascular, Lewy body, frontotemporal and mixed dementia)

Description

Inclusion Criteria:

1. Dementia diagnosed according to DSM -5\ with a total Mini-Mental State Examination score < 24 (or < 22 according to educational state), together with a Modified Mini-Mental State Examination (3MS) score < 79 to confirm cognitive impairment.
2. Mild cognitive impairment diagnosed according to established diagnostic criteria according to DSM -5.
3. Men or women of at least 50 years of age.
4. Reliable in individual data and willing to make themselves available for the duration of the study.
5. Clear written informed consent obtained from a first-degree relative for each patient participant, and from the control participant himself/herself.

Exclusion Criteria:

• age below 50 years .

  • other neurological disorders or psychiatric disorders; previous history of stroke; metabolic disturbance; other major medical illnesses; epilepsy; inflammatory, autoimmune, or infectious disease; metallic objects in the body; craniotomy in the past.
  • Presence of clinically significant medical or psychiatric condition that may increase the risk associated with the study
  • MRI contraindication (pacemaker, metallic implants, severe claustrophobia).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Dementia; according toDSM -5 , with a total Mini-Mental State Examination score < 24 (or < 22 according to educational state), together with a Modified Mini-Mental State Examination (3MS) score < 79 to confirm cognitive impairment
Mild Cognitive impairment; impairment diagnosed according to established diagnostic criteria
control; healthy group matched age, sex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of Glial Fibrillary Acidic Protein (GFAP)main outcome	Measured in picograms per milliliter (pg/mL) via automated chemiluminescent immunoassay (Lumipulse or Alinity platform) or ELISA, from venous blood collected in EDTA tubes	Baseline (single time point)
Hippocampal Volume on MRI, Whole-Brain Volume on MRI,Ventricular Volume on MRI	Measured in cubic millimeters (mm³), normalized to total intracranial volume, derived from 3-Tesla 3D T1-weighted MPRAGE MRI using automated segmentation software (FreeSurfer)	Baseline (single time point)
EEG Band Power Alpha , beta , delta , theta	Absolute spectral power (µV²) in the different frequency band , derived from resting-state EEG recorded with a 19-channel 10-20 electrode montage	Baseline (single time point)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Plasma GFAP and MRI Volumetric Measures Across Dementia Etiological Subtypes	Pearson/Spearman correlation coefficient between plasma GFAP concentration (pg/mL) and MRI-derived regional brain volumes (mm³), calculated separately within Alzheimer's, vascular, Lewy body, frontotemporal, and mixed dementia subgroups	Baseline (single time point)
Correlation Between Plasma GFAP and EEG Spectral Power Measures Across Dementia Etiological Subtypes	Pearson/Spearman correlation coefficient between plasma GFAP concentration (pg/mL) and EEG band power (µV²), calculated separately within Alzheimer's, vascular, Lewy body, frontotemporal, and mixed dementia subgroups	Baseline (single time point)

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): October 10, 2026
• Primary Completion (Estimated): October 10, 2028
• Study Completion (Estimated): March 10, 2029

Study Registration Dates

• First Submitted: September 1, 2026
• First Submitted That Met QC Criteria: September 4, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 4, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: dementia; cognition; mild cognitive impairment; GFAP
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Dementia
• Other Study ID Numbers: Biomarkers of cognition

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No