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.

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.

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).