Hyperhomocysteinemia in Alzheimer's Disease

Not yet recruiting

• Conditions: Alzheimer Disease; Homocystinemia
• Interventions: Other: Retrospective study of clinical features

• Registration Number: NCT05793372
• Lead Sponsor: Central Hospital, Nancy, France

Brief Summary

Alzheimer's disease (AD) is the most common neurodegenerative disease. Age is its main risk factor. AD is a multifactorial disease, combining genetic and environmental risk factors. Autosomal dominant mutations have been identified (PSEN1, PSEN2, APP), leading to earlier and more severe forms of the disease. Other genetic risk factors have been identified, such as the ε4 allele of the APOE gene. . The environment also plays a major role, with the identification of several risk factors such as air pollution or nutritional deficiencies.

AD patients frequently present hyperhomocysteinemia, a consequence of a dysfunction of monocarbon metabolism. Homocysteine is an amino acid involved in the metabolism of methionine and cysteine. High concentrations of homocysteine can be deleterious to the central nervous system.

Most prospective studies have shown that elevated homocysteine is a predictor of undefined cognitive impairment or AD. Other studies have focused on clinical data and, in particular, on cognitive function. For example, a meta-analysis found an inverse correlation between MMSE score and homocysteine level.

Thus, our study seeks to evaluate the impact of hyperhomocysteinemia on the severity and early onset of AD, while knowing the presence or absence of genetic risk factors associated with AD.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-03-20
• Study First Submitted QC: 2023-03-20
• Study First Posted: 2023-03-31
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-16
• Last Update Posted: 2023-05-17
• Study Start: 2023-06
• Primary Completion: 2023-06
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Clinical diagnosis of Alzheimer's disease
• Positive CSF biomarkers
• age of onset < 75 years
• already benefited from a previous research of Alzheimer's disease genetic features (PSEN1, PSEN2, APP, APOE)
• already benefited from a previous research of homocysteine cycle (monocarbon metabolism) by complete exome/clinical exome or panel

Exclusion Criteria

• patient refusal

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
patients with Alzheimer's Disease	Retrospective study of clinical features	Patients with Alzheimer's disease

Primary Outcome Measures

Name	Time	Method
Correlation between homocysteine levels and the severity/early onset of Alzheimer's disease	baseline	Mesure of homocysteine levels Mesure of MiniMental State Evaluation (MMSE), age of symptoms onset

Secondary Outcome Measures

Name	Time	Method
Evaluation of the frequency of hyperhomocysteinemia in a homogeneous population of patients with Alzheimer's disease.	baseline	measurement of homocysteine levels in our cohort (µmol/L)
Evaluation of the genetic characteristics of Alzheimer's disease Evaluation of the genetic characteristics of homocysteine monocarbon metabolism.	baseline	search for an autosomal dominant mutation (APP, PSEN1 or PSEN2) or a risk factor mutation for Alzheimer's disease (TREM2, SORL1, ABCA7) and APOE status search for a mutation in the genes of monocarbon metabolism
Evaluation of the frequency of vitamin B deficiencies in a homogeneous population of patients with Alzheimer's disease.	baseline	measurement of B1,B6,B9 and B12 levels in our cohort (nmol/L)