Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease

NCT06224920 | Completed DMC

• 1 other identifier: 17-755 and 17-569
• Study Type: observational
• Target: 140
• Locations: 0 countries
• Sites: N/A

Brief Summary

The temporal sequence of microglial activation, changes in functional and structural connectivity and the progression of neurocognitive deficits has not been conclusively clarified. To date, there have been no studies of the topographical and pathogenetic relationship between microglial activation and network degeneration. The main aim of the present study is to investigate the relationships between functional, structural MRI connectivity and microglial activation at different stages of AD in a multimodal approach. Genetic predisposition and biomarkers in blood and cerebrospinal fluid will also be taken into account in order to close the explanatory gap in pathogenesis between the known molecular pathological changes and their effects at system level in an integrative approach.

Conditions

Alzheimer Disease; Corticobasal Syndrome

Keywords

Alzheimer´s disease; corticobasal degeneration; microglial activation; neuroinflammation; amyloid; tau protein

Outcome Measures

Primary Outcomes (3)

• association of cerebral connectivity with microglia activation patterns

  association between functional/structural connectivity and TSPO SUVR

  until 06/2024

• Individual regional associations between Aβ-, tau- and neurodegeneration with microglial activation

  association of regional amyloid and tau with microglial activation (measured by TSPO-PET)

  until 06/2024

• validation of blood-based biomarkers in the differentiation of AD, SCI and CBS cases

  comparison of AD-related biomarkers (pTau181, Abeta1-42/1-40), plasma apolipoprotein E and inflammatory biomarkers (GFAP, NfL)

  until 06/2024

Study Arms (3)

Alzheimer´s disease spectrum

MCI-AD patients Evidence of minor cognitive impairment with essentially preserved everyday competence and evidence of reduced Aβ42 concentration in the cerebrospinal fluid. Score in the CERAD word list 1.5 SD below the normal range. Patients with AD-dementia Evidence of pronounced cognitive impairment and relevant impairment of everyday life and evidence of reduced Aβ42 concentration in the cerebrospinal fluid (diagnostic criteria (NIA-AA fulfilled)).

Diagnostic Test: magnetic resonance imaging; Other: electroencephalography; Diagnostic Test: blood and CSF biomarker; Diagnostic Test: positron emission tomography; Diagnostic Test: neuropsychological test

corticobasal syndrome due to probable 4 repeat taupathy

Evidence of the typical clinical picture of an atypical Parkinson's syndrome with onset of symptoms \> 1 year. No evidence of reduced Aβ42 concentration in the cerebrospinal fluid. Fulfillment of the revised Armstrong criteria for probable CBS or the Movement Disorder's Society criteria for suggestive/possible PSP-CBS.

Diagnostic Test: magnetic resonance imaging; Other: electroencephalography; Diagnostic Test: blood and CSF biomarker; Diagnostic Test: positron emission tomography; Diagnostic Test: neuropsychological test

subjective congnitive decline

Subjective memory impairment, with age-appropriate unremarkable neurocognitive test battery (CERAD) and no evidence of reduced Aβ42 concentration or increased total tau or phospho-tau concentration in the cerebrospinal fluid. Subjective cognitive deterioration over a period of 6 months to 5 years.

Diagnostic Test: magnetic resonance imaging; Other: electroencephalography; Diagnostic Test: blood and CSF biomarker; Diagnostic Test: positron emission tomography; Diagnostic Test: neuropsychological test

Interventions

magnetic resonance imaging DIAGNOSTIC_TEST

MRI data acquisition was performed on a 3 Tesla MRI scanner with parallel transmission and reception technology (Skyra Magnetom, Siemens Healthcare, Erlangen, Germany). Imaging is performed with a maximum gradient strength of 45mT/m and a maximum slew rate of 200 T/m/s and a 64-element head coil.

Alzheimer´s disease spectrum; corticobasal syndrome due to probable 4 repeat taupathy; subjective congnitive decline

electroencephalography OTHER

A 20-channel resting EEG (Brain Products, Gilching, Germany) is recorded as part of routine clinical diagnostics in the Department of Psychiatry and Psychotherapy at the LMU to rule out focal neurophysiological pathologies. Within the scope of the present study, an extended examination will be carried out, which includes a 64-channel EEG, including a passive visual paradigm. After completion of the clinical evaluation, the neurophysiological changes in resting activity will be scientifically analyzed in comparison to the MRI and PET data.

Also known as: eeg

Alzheimer´s disease spectrum; corticobasal syndrome due to probable 4 repeat taupathy; subjective congnitive decline

blood and CSF biomarker DIAGNOSTIC_TEST

Aβ1-42 and 1-40, total tau protein and phosphorylated tau protein 181 (p-Tau), apolipoprotein E (APOE), soluble TREM2 protein, neurofilament light chain and glial fibrillary protein (GFAP) will be determined.

Alzheimer´s disease spectrum; corticobasal syndrome due to probable 4 repeat taupathy; subjective congnitive decline

positron emission tomography DIAGNOSTIC_TEST

According to an established and standardized protocol, PET scans are performed with the TSPO receptor ligand \[18F\]-GE-180, \[18F\]flutemetamol for assessment of fibrillar Aβ 162 accumulation and the Tau ligand \[18F\]-PI-2620. In brief, \[18F\]GE-180 TSPO PET images (mean dose: 177 ± 17 MBq) with an emission window of 60-80 min after injection will be acquired to measure the activation of glial cells. \[18F\]Flutemetamol Aβ PET images (average dose: 182 ± 11 MBq) are acquired with an emission window of 90-110 min after injection to assess fibrillar Aβ accumulation. Dynamic \[18F\]PI-2620 tau PET (average dose: 186 ± 14 MBq) with an emission window of 0-60 minutes after injection are performed for quantification of tau aggregation. Static images of the late phase (20-40 min) are reconstructed. These images are used for further processing and analysis.

Also known as: PET

Alzheimer´s disease spectrum; corticobasal syndrome due to probable 4 repeat taupathy; subjective congnitive decline

neuropsychological test DIAGNOSTIC_TEST

Trained psychologists at the Memory Clinic of the LMU Hospital administered the CDR, CERAD-NB and Mini-Mental State Examination (MMSE). The CERAD-NB battery was used to generate a total score for the six subscales: semantic fluency (animals/60 s), modified Boston naming test, lexical items, construction practice, lexical items retrieval, and lexical items discrimination, with higher scores indicating better performance.

Alzheimer´s disease spectrum; corticobasal syndrome due to probable 4 repeat taupathy; subjective congnitive decline

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

recruitment of participants via the outpatient clinics of Department of Psychiatry and Psychotherapy, Department of Neurology and Institute of Stroke and Dementia Research (LMU hospital)

You may qualify if:

• Informed consent for the additional examinations, written declaration of consent
• Constant pharmacotherapy in a period of one week before the MRI/EEG/PET examination

You may not qualify if:

• Existence of legal guardianship/restricted capacity to consent
• Other severe concomitant psychiatric illnesses, e.g. schizophrenia, bipolar affective disorder
• Clinically relevant depressive symptoms (Beck Depression Inventory, BDI, score \> 17/GDS \> 5)
• Acute suicidal tendencies
• Drug, medication or alcohol abuse at the time of the study
• Severe traumatic brain injury (\> 2nd degree TBI) in the medical history or 1st degree within the last 3 months.
• Evidence of structural damage to the basal ganglia or brainstem
• Severe neurological diseases (such as disc prolapse in the last 6 months, sensory, motor or autonomic polyneuropathies)
• Severe internal diseases (such as manifest arterial hypertension, severe heart disease, pacemaker, respiratory insufficiency)
• Any electronic implants (e.g. pacemakers) or other MRI and/or PET contraindications
• Malignant diseases of any kind in the last 5 years, severe active infectious diseases, chronic and systemic skin diseases
• Bone diseases (such as Paget's disease, osteoporosis with spontaneous fractures, recent fractures)
• Other circumstances which, in the opinion of the investigator, speak against the patient's participation in this study
• Occupational or other radiation exposure \>15 mSv/a

Sponsors & Collaborators

• Ludwig-Maximilians - University of Munich: lead

Biospecimen

Retention: SAMPLES WITH DNA

Biospecimen collection and processing data is captured by CentraXX (Kairos GmbH, Bochum, Germany), a fully integrated laboratory automation infrastructure. Biological specimens (DNA, RNA, serum, plasma, etc.) are processed in the laboratory using automated equipment (ChemagicStar, decapper/barcode reader and a StarPlus unit, Hamilton Robotics GmbH, Martinsried) and stored at -80 °C in an automated specimen storage and management unit (BIOS M unit, Hamilton Storage GmbH, Bonaduz, Switzerland).

MeSH Terms

Conditions

Alzheimer Disease; Corticobasal Degeneration; Neuroinflammatory Diseases; Frontotemporal Dementia

Interventions

Magnetic Resonance Imaging; Blood Specimen Collection; Positron-Emission Tomography

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Image Enhancement; Photography; Radionuclide Imaging; Diagnostic Techniques, Radioisotope

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principle investigator

Study Record Dates

• First Submitted: January 16, 2024
• First Posted: January 25, 2024
• Study Start: January 1, 2017
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: July 4, 2025

Record last verified: 2025-07