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NCT Number: NCT06874231

Brain Connectivity Marker for Alzheimer's Disease

The main purpose of this project is to establish whether changes in brain connectivity can be used to predict the development of Alzheimer's disease (AD).

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Key information

Age range

40 year–85 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Karolinska University Hospital

Stockholm, Solna, 171 64, Sweden

Location status: Recruiting

Location contact

Simona Sacuiu, MD, PhD

CONTACT

[email protected]

0734352012

About this study

To achieve this aim, the investigators will perform six different studies that have been designed to achieve the following specific objectives:

1.1. Identify changes of brain connectivity in individuals who show abnormal AD amyloid biomarkers in the cerebrospinal fluid and blood.

1.2. To assess the correlation between brain connectivity changes and biomarkers of synaptic dysfunction and inflammation as well as alterations of electrical brain signals.

1.3. Establish whether alterations of brain connectivity could be improved after patients start treatment with cholinesterase inhibitors.

1.4. Assess differences in brain connectivity between patients receiving treatment with statins and those not taking this medication.

1.5. Determine whether brain connectivity changes can predict longitudinal cognitive decline and conversion to AD dementia.

1.6. Assess whether different microorganisms can grow more rapidly in the cerebrospinal fluid from AD patients compared to controls and whether their levels are associated with brain connectivity.

1.7. Evaluate the relationship between brain connectivity and the integrity of the locus coeruleus, which is the earliest site of AD pathology

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Inclusion criteria for subjects with subjective cognitive complaints:
  • MMSE (Mini-mental test) or MoCA (Montreal Cognitive Assessment) points between 26 and 30.
  • Absence of cognitive impairment.
  • Memory problems reported by the participant/family member.
  • Do not fulfill criteria for mild cognitive impairment or dementia.
  • Must speak and understand Swedish.
  • Inclusion criteria for patients with mild cognitive impairment:
  • MMSE (Mini-mental test) or MoCA (Montreal Cognitive Assessment) points between 24 and 30.
  • Impaired memory function.
  • Do not fulfill criteria for dementia.
  • Must speak and understand Swedish.
  • Must have abnormal cerebrospinal fluid amyloid-β 42/40 ratio levels, which is a biomarker of Alzheimer's disease.
  • Specific inclusion criteria for patients with Alzheimer's disease:
  • MMSE (Mini-mental test) or MoCA (Montreal Cognitive Assessment) points between 18 and 28.
  • Impaired memory function in addition to impaired executive abilities, language function, visuospatial ability and/or attention/psychomotor speed.
  • Meet NINCDS-ADRDA and DSM-IV criteria for probable Alzheimer's disease.
  • Must speak and understand Swedish.
  • Must have abnormal spinal fluid amyloid-β 42/40 ratio levels, which is a biomarker of Alzheimer's disease.

Exclusion criteria

  • Alcohol or drug abuse.
  • Unstable somatic disease or organ failure.
  • Refuse to cerebrospinal fluid testing and/or blood sampling, neuropsychological testing, brain imaging, electroencephalogram or magnetoencephalogram.

In addition, participants who have claustrophobia or some form of metal implant in their body that may interfere with the brain imaging scan will be excluded from the study.

Treatment and study plan

Neuroimaging

Other

The investigators will collect imaging sequence, cognitive test scores, clinical data and biofluid samples

Other names: Cognitive assessment

Primary outcomes

  1. Brain connectivity can predict the development of Alzheimer's disease

    Time frame: 4 years

    The investigators will build a multilayer network for each patient using DWI and fMRI images, following a methodology similar to that described in Multiplex Connectome Changes Across the Alzheimer's Disease Spectrum Using Gray Matter and Amyloid Data. Specifically, each patient's brain connectivity will be modeled as a multiplex network, where distinct imaging modalities define different layers. The structural connectivity layer will be derived from diffusion-weighted imaging (DWI), capturing white matter fiber tract connections between brain regions. The functional connectivity layer will be built using functional MRI (fMRI), measuring temporal correlations of neural activity across regions. Nodes in the network will correspond to anatomically defined brain regions, and inter-layer edges will be established to link homologous regions across layers, enabling integration of structural and functional information.

Secondary outcomes

  1. Relationship between multilayer connectivity and other imaging sequences, cognition and biofluid biomarkers

    Time frame: 4 years

    The investigators will measure the association between multilayer brain connectivity with biomarkers and clinical measures from the participants, including markers of amyloid, tau, vascular pathology and tests measuring memory, executive function, language and visuospatial skills. These analyses will be conducted using linear regression and linear mixed effects models for longitudinal outcomes.

Study contacts

Contact information is provided by the study sponsor or research team.

Joana B. Pereira, PhD

CONTACT

[email protected]

+46709966186

Sponsors and collaborators

Lead sponsor

Karolinska Institutet

Other

Collaborators

  • The Swedish Research Council

Registry information

Official study title

Clinical Application of a Brain Connectivity Marker for Early Detection of Alzheimer's Disease

Acronym: BRAINCONN

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Mar 13, 2025
Registry last updated
Mar 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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