Hyperhomocysteinemia in Alzheimer's Disease (Hcy-MA)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease; Homocystinemia
• Intervention / Treatment: Other: Retrospective study of clinical features

• Study Type: Observational
• Enrollment (Anticipated): 43

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients with Alzheimer's Disease; Patients with Alzheimer's disease	Other: Retrospective study of clinical features; Retrospective study of clinical features

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the genetic characteristics of Alzheimer's disease Evaluation of the genetic characteristics of homocysteine monocarbon metabolism.	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	baseline
Evaluation of the frequency of hyperhomocysteinemia in a homogeneous population of patients with Alzheimer's disease.	measurement of homocysteine levels in our cohort (µmol/L)	baseline
Evaluation of the frequency of vitamin B deficiencies in a homogeneous population of patients with Alzheimer's disease.	measurement of B1,B6,B9 and B12 levels in our cohort (nmol/L)	baseline

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): May 17, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Nutrition Disorders; Genetic Diseases, Inborn; Neurodegenerative Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Metabolism, Inborn Errors; Dementia; Tauopathies; Malabsorption Syndromes; Amino Acid Metabolism, Inborn Errors; Vitamin B Deficiency; Alzheimer Disease; Hyperhomocysteinemia
• Other Study ID Numbers: 2023PI049

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No