Hyperhomocysteinemia in Alzheimer's Disease

Study Overview
=================
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.

Official Title
-----------------
Hyperhomocysteinemia in Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease, Homocystinemia

Intervention / Treatment
-----------------
* Other: Retrospective study of clinical features


Participation Criteria
=================
Eligibility Criteria
-----------------
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with Alzheimer's Disease<br>Patients with Alzheimer's disease | Other: Retrospective study of clinical features<br>* Retrospective study of clinical features<br>|

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 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 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 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 |