Circadian Rhythm and Other Factors in Memory Clinic Patients

Recruiting

• Conditions: Dementia
• Interventions: Other: Questionnaire; Other: Clinical examination; Other: Accelerometer port; Other: Eye examination

• Registration Number: NCT05977712
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The CIRCAME study is a bicentric study of patients from 2 memory clinics in Paris. The main objective is to identify circadian rhythm components and other individual risk factors (sociodemographic, behavioral, and health related factors) associated with the diagnosis of subtypes (AD, Lewy bodies, vascular, frontotemporal dementia) and stages (cognitively healthy, mild cognitive impairment, clinical dementia) of dementia, independent of known risk factors (sociodemographic and genetic) and assess the relevance of use of these factors in primary care for screen of dementia including subtypes and stages. A secondary objective is to determine factors associated with progression of the disease, in terms of cognitive decline and limitations in activities of daily living, as well as progression to dementia among cognitively healthy controls and patients with mild cognitive impairment, up to 15 years after the inclusion period.

Detailed Description

The diagnosis of Alzheimer's disease and other related dementias is mainly based on assessment of cognitive, behavioral and neuropsychological symptoms, functional limitations and imaging data/cerebrospinal fluid (CSF) biomarkers in some cases. These measures are primarily used in specialized clinics leading to a potential large number of dementia cases not being diagnosed. With population ageing, the number of people living with dementia is increasing and there is an urgent need for cost-effective, scalable tool for early, accurate screening of dementia cases, including both AD and other types of dementia, in primary care. Furthermore, the factors associated with the progression of the different types of dementia are still poorly understood, limiting the prospects for intervention to improve the quality of life of patients and their caregivers and to slow the progression of the disease.

This project aims to identify circadian rhythm components and other individual risk factors that could be used in primary care for dementia diagnosis (including its subtypes: AD, Lewy bodies, vascular, frontotemporal dementia) and stages (cognitively healthy, mild cognitive impairment, clinical dementia). A secondary objective is to determine factors associated with progression of the disease, in terms of cognitive decline and limitations in activities of daily living, as well as progression to dementia among cognitively healthy controls and patients with mild cognitive impairment.

This will be achieved using data from 1500 patients from 2 memory clinics in Paris from who data on sociodemographic, behavioral, and health related factors (such as reported sleep disturbance, plasma biomarkers, retina measures (in a subsample, CIRCAME-EYE)) will be measured at inclusion interview. Baseline examination will also include a wrist-mounted device for a measure of circadian rhythm and its related behaviors (physical activity and sleep), for which disruptions are thought to characterize dementia subtypes and stages. Information on dementia diagnosis and stages will come from memory clinic routine visits at the time of the inclusion; they will include subtypes (AD, Lewy bodies, vascular, frontotemporal dementia), cognitive stages (cognitively healthy, mild cognitive impairment, clinical dementia) and AD stages based on CSF biomarkers and clinical measures. Information on progression of the disease (change in cognitive function using the mini-mental status examination, change in limitations in activity of daily living) and incidence of dementia, institutionalization and mortality will be retrieved from patients' routine visits at memory clinics up to 15 years after the inclusion period.

Study Timeline

• Study First Submitted: 2023-07-28
• Study First Submitted QC: 2023-08-03
• Study First Posted: 2023-08-04
• Status Verified: 2024-03
• Study Start: 2024-03-06
• Last Update Submitted: 2024-03-07
• Last Update Posted: 2024-03-12
• Primary Completion: 2027-03
• Study Completion: 2042-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1500

Inclusion Criteria

• Patient of legal age (18 or over)
• Signed informed consent form
• Patient affiliated to the french social security system

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Exclusion Criteria

• Skin allergy to plastic
• Diagnosis of psychiatric disorder that can explain all cognitive symptoms
• Inability to come accompanied for patients with a Mini-Mental State Examination (MMSE) cognitive score ≤20 or a clinician assessment indicating the need to be accompanied (e.g. wheelchair use, agitation)
• Patient of legal age and subject to a legal protection measure (guardianship, curatorship)
• Participation at the time of inclusion and during the 9-day period of wearing the accelerometer in interventional research with potential impact on circadian rhythm

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
CIRCAME	Questionnaire	This is the full cohort of patients that compose the CIRCAME study (N estimated = 1500)
CIRCAME-EYE ancillary study	Questionnaire	Patients from CIRCAME seen at the Fernand-Widal hospital who will also undergo an eye examination (CIRCAME-EYE, N estimated = 1100, a sub-group of CIRCAME)
CIRCAME	Clinical examination	This is the full cohort of patients that compose the CIRCAME study (N estimated = 1500)
CIRCAME	Accelerometer port	This is the full cohort of patients that compose the CIRCAME study (N estimated = 1500)
CIRCAME-EYE ancillary study	Clinical examination	Patients from CIRCAME seen at the Fernand-Widal hospital who will also undergo an eye examination (CIRCAME-EYE, N estimated = 1100, a sub-group of CIRCAME)
CIRCAME-EYE ancillary study	Accelerometer port	Patients from CIRCAME seen at the Fernand-Widal hospital who will also undergo an eye examination (CIRCAME-EYE, N estimated = 1100, a sub-group of CIRCAME)
CIRCAME-EYE ancillary study	Eye examination	Patients from CIRCAME seen at the Fernand-Widal hospital who will also undergo an eye examination (CIRCAME-EYE, N estimated = 1100, a sub-group of CIRCAME)

Primary Outcome Measures

Name	Time	Method
Dementia subtypes and stages	At inclusion (2024-2025), in 2026 and every 3 years up to 2042	Dementia subtypes and stages will be defined on routine visits at the memory center and categorised as: Alzheimer's disease, vascular dementia, Lewy body dementia, frontotemporal dementia), as having mild cognitive impairment (differentiating AD form of MCI and others), or being cognitively healthy.; This outcome will be examined cross-sectionally first (at inclusion) and, among those with MCI and healthy controls, prospectively over time (up to 15 years after the inclusion period).
Alzheimer's disease stages	At inclusion (2024-2025), in 2026 and every 3 years up to 2042	AD stages will be based on CSF Aβ peptide level (Aβ42/40 ratio) to assess the A+ criterion, p-Tau 181 to assess the T+ criterion, and clinical examination to assess the CogFI+ criterion (cognitive impairment and/or neurobehavioural symptoms with functional impact on daily life).; This analysis will be among those with CSF biomarkers measured as part of their routine visit at the memory clinics.

Secondary Outcome Measures

Name	Time	Method
Institutionalization, hospitalization and death	Incidence between inclusion and 2026 and every 3 years up to 2042	Information will come from memory clinics and electronic health records.
Fluid based biomarkers of dementia	At inclusion	Association of the different exposure variables with plasma and csf biomarkers of dementia will be examined.; Plasma biomarkers include 1) Amyloid β 42/40 ratio, a marker of AD pathology, although probably less robust than the CSF Aβ 42/40 ratio; 2) phosphorylated tau (p-tau) for detection of early AD-related tauopathy and disease staging; 3) neurofilament light (NfL), a marker of neurodegeneration in all neurodegenerative diseases, and 4) glial fibrillary acidic protein (GFAP), a marker of astrocytosis, found as early as in pre-amyloid AD disease stages.; CSF biomarkers include Aβ42 and Aβ40 peptides, total and phosphorylated tau proteins (when done in routine care).
Cognitive function	At inclusion (2024-2025), and change between inclusion and 2026 and every 3 years up to 2042	Cognitive tests include the mini-mental status examination test and the MemScreen test. They will be evaluated at inclusion and during routine visit at the memory clinics. Association with scores at inclusion and changes between inclusion and several time points will be examined.
Limitations in activity of daily living (ADL) and instrumental activity of daily living (IADL)	At inclusion (2024-2025), and change between inclusion and 2026 and every 3 years up to 2042	Limitations in ADL (dressing, walking, bathing, eating, continence, using toilet) and IADL (cooking, shopping for grocery, telephone calls, taking medication, using transports, managing money).

Trial Locations

Locations (2)

Centre de neurologie Cognitive / CMRR; 🇫🇷 Paris, France

Hôpital de Jour Gériatrique et consultation mémoire; 🇫🇷 Paris, France