NCT07089303 - Alzheimer's Disease Multinuclear Imaging Neuro-Enhanced Resolution (AD-MINER) | Crick

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Inclusion Criteria: * Age 55-90 years (inclusive). * Willing and able to participate in baseline assessment and longitudinal follow-up; voluntary provision of biospecimens and personal information, and commitment to complete all follow-up visits. * Able to undergo MRI scanning (no contraindications to MRI). * Group-specific cognitive criteria: CN: No subjective memory complaints beyond age expectation (confirmed by study partner); MMSE score 26-30 (inclusive; exceptions permitted for participants with \<8 years of education with principal investigator approval; CDR = 0, memory box = 0; Normal cognitive and daily functioning, no significant impairment. MCI: Subject, partner, or physician reports subjective memory concerns; MMSE criteria same as CN group; CDR = 0.5 (memory box ≥0.5); General cognition and function relatively preserved; does not meet criteria for AD. AD: Subject, partner, or physician reports subjective memory concerns; MMSE score \<26 (inclusive; exceptions as above); CDR = 0.5 or 1.0; Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) probable AD diagnostic criteria or 2024 National Institute on Aging-Alzheimer's Association (NIA-AA) criteria (e.g., positive Pittsburgh compound B (PIB) and tau). Exclusion Criteria: * Self-reported or MRI-detected major neurological diseases other than AD: including but not limited to stroke (cerebral hemorrhage, infarction), congenital intellectual disability, intracranial tumors, epilepsy, Parkinson's disease, Huntington's disease, normal pressure hydrocephalus, progressive supranuclear palsy, multiple sclerosis, severe head trauma with persistent deficits, etc. * Severe psychiatric disorders (e.g., schizophrenia requiring medication control) or other known brain structural abnormalities. * Significant organ failure (heart, liver, kidney, etc.), malignant tumors, or short life expectancy making completion of follow-up unlikely. * Contraindications to MRI (e.g., claustrophobia, incompatible pacemaker, aneurysm clip, artificial heart valve, cochlear implant, or other metallic implants). * Other clinical history or examination findings judged by investigators as potentially unsafe for MRI or follow-up. * Use of investigational drugs within one month prior to enrollment or during the study.

Outcomes

Primary Outcomes

Change from Baseline in Regional Brain Sodium Concentration (mmol/L) Measured by 7 T ²³Na-MRI

Quantitative regional brain sodium concentration measured by 7 T sodium (²³Na) MRI; units mmol/L; higher values indicate increased sodium concentration.

Time frame: Baseline to 1 year

Change from Baseline in Resting-State Fractional Amplitude of Low-Frequency Fluctuations（fALFF, unitless) Measured by 7 T fMRI

Fractional Amplitude of fALFF averaged within gray-matter mask (unitless; higher = greater spontaneous activity).

Time frame: baseline to 1year

Change from Baseline in Mean Apparent Diffusion Coefficient (ADC) (×10-³ mm²/s) Derived from Dynamic Diffusion-Weighted Imaging (DynDWI)

Mean ADC (×10-³ mm²/s) derived from DynDWI; higher values indicate increased diffusivity.

Time frame: Baseline to 1 year

Change From Baseline in Fractional Anisotropy (FA, unitless)

Change from baseline in DTI-derived FA values in major white matter tracts; higher FA indicates greater microstructural integrity.

Time frame: Baseline to 1 year

Change From Baseline in Mean Diffusivity (MD, ×10-³ mm²/s)

Change from baseline in DTI-derived MD values in major white-matter tracts; higher MD indicates increased water diffusivity (×10-³ mm²/s).

Time frame: Baseline to 1 year

Secondary Outcomes

Change from Baseline in Montreal Cognitive Assessment (MoCA) Total Score (0-30, points)

Higher scores indicate better global cognition.

Time frame: Baseline to 1 year

Change from Baseline in Clinical Dementia Rating (CDR) Global Score (0-3, points)

Higher scores indicate more severe dementia.

Time frame: Baseline to 1 year

Change from Baseline in Mini-Mental State Examination (MMSE) Total Score (0-30, points)

Lower scores indicate greater impairment.

Time frame: Baseline to 1 year

Change From Baseline of the Auditory Verbal Learning Test (AVLT) Total Learning Score

AVLT total learning score is the sum of Trials N1-N6 (each trial scored 0-15; total range 0-90); higher scores indicate better verbal memory.

Time frame: baseline to 1year

Change from Baseline in Rey-Osterrieth Complex Figure Test (ROCF) Combined Recall Score (0-72, points)

Combined Recall = Immediate Recall (0-36) + Delayed Recall (0-36), scored with the 36-point Osterrieth method; range 0-72. Higher scores indicate better visuospatial (visual) memory.

Time frame: baseline to 1year

Change From Baseline of the Clock Drawing Test (CDT) Score (0-5, points)

CDT score ranges 0-5; higher scores indicate better visuospatial and executive function.

Time frame: Baseline to 1 year

Change From Baseline of the Boston Naming Test (BNT) Total Score (0-60, points)

BNT total score ranges 0-60; higher scores indicate better confrontational naming ability.

Time frame: Baseline to 1 year

Change from Baseline in Digit Span Test (DST) Total Score (0-15, points)

Forward (0-8) + backward (0-7); higher = better attention/working memory.

Time frame: Baseline to 1 year

Change from Baseline in Symbol Digit Modalities Test (SDMT) Total Score (correct matches per 90 s)

SDMT total score is the number of correct symbol-digit matches in 90 seconds (typical range 0-110); higher scores indicate better processing speed and attention.

Time frame: Baseline to 1 year

Change from Baseline in Stroop Color-Word Test (SCWT) Incongruent Condition Completion Time (seconds)

Shorter time indicates better cognitive flexibility and inhibition.

Time frame: Baseline to 1 year

Change from Baseline in Neuropsychiatric Inventory (NPI) Total Score (0-144, points)

NPI total score ranges 0-144; higher scores indicate more severe neuropsychiatric symptoms.

Time frame: Baseline to 1 year

Change from Baseline in Hamilton Anxiety Rating Scale (HAMA) Total Score (0-56, points)

HAMA total score ranges 0-56; higher scores indicate more severe anxiety symptoms.

Time frame: Baseline to 1 year

Change from Baseline in Hamilton Depression Rating Scale (HAMD) Total Score (0-52, points)

HAMD total score ranges 0-52; higher scores indicate more severe depressive symptoms.

Time frame: Baseline to 1 year

Change from Baseline in Symptom Checklist-90 (SCL-90) Total Score (90-450, points)

SCL-90 total score ranges 90-450; higher scores indicate greater overall psychological distress.

Time frame: Baseline to 1 year

Change from Baseline in Activities of Daily Living (ADL) Scale Score (0-100, points)

ADL total score ranges 0-100; higher scores indicate greater independence in basic self-care tasks.

Time frame: Baseline to 1 year

Change from Baseline in Pittsburgh Sleep Quality Index (PSQI) Total Score (0-21, points)

PSQI total score ranges 0-21; higher scores indicate poorer sleep quality over the past month

Time frame: Baseline to 1 year

Change from Baseline in Trail Making Test (TMT) B-A Difference Score (seconds)

Difference score calculated as Part B completion time minus Part A completion time (in seconds). Lower scores indicate better executive function after adjusting for processing speed.

Time frame: Baseline to 1 year

Plasma Biomarkers of AD

Percent changes from baseline in: amyloid-beta 40 and 42 (Aβ40, Aβ42), phosphorylated tau 181 and 217 (p-tau181, p-tau217) and neurofilament light (NfL); concentrations in pg/mL.

Time frame: Baseline to 1 year

Change from Baseline in Hippocampal Volume (mm³) by FreeSurfer

Bilateral hippocampal volume segmented with FreeSurfer; units mm³.

Time frame: Baseline to 1 year

Number of participants with new cerebral microbleeds detected by susceptibility-weighted imaging (SWI)

New microbleeds are defined as the appearance of ≥1 new hypointense lesion on SWI compared to baseline.

Time frame: Baseline to 1 year

Change from Baseline in Brain Perivascular Spaces (PVS) Burden (semi-quantitative score)

Description: PVS scored 0-4 in basal ganglia and 0-4 in centrum semiovale on 7 T MRI; global burden is the sum (0-8); higher scores indicate greater PVS load.

Time frame: Baseline to 1 year

Alzheimer's Disease Multinuclear Imaging Neuro-Enhanced Resolution (AD-MINER)

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes