N-Terminal pro-Brain Natriuretic Peptide, Homocysteine and Methylenetetrahydrofolate Reductase Gene Polymorphism in Elderly Depressed and Mild Cognitive Impairment Patients

There is increasing evidence that vascular disease contributes to cognitive
impairment and depression. Secretion of N-Terminal pro-Brain Natriuretic Peptide
(NT-proBNP) increases in several cardiac illnesses, mak ing this neurohormone a
reliable diagnostic and prognostic biomark er of cardiovascular risk . Homocysteine
(Hcy) is harmful to neurons and blood vessels, including the cerebral
microvasculature. It is possible that such effects contribute to the cascade of events
that leads to cognitive decline, dementia, and depression in later life. Hcy is produced
during the metabolism of the essential amino-acid methionine, its plasma level can be
influenced by factors such as vitamin deficiency, renal function, and a common
mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, where cytosine
is replaced by thymine (C→T) at nucleotide position 677. The aim of the present
study was to evaluate the role of NT-proBNP, Hcy, folate , and MTHFR gene
polymorphism in late life mild cognitive impairment (MCI) and depression, and to
determine the association between homozygous carriers of the TT genotype and Hcy
and NT-proBNP on one-hand and depressive and cognitive scores on other-hand. T he
study included 60 elderly patients, they attended the Outpatient Clinic for treatment
of depression (group I, n=32) and/or MCI (group II, n=28). In addition to a control
group (group III, n=20) which matched to the patients with respect to age and gender
with no previous history of psychiatric diseases. Both plasma NT-proBNP and Hcy
levels were assayed by ELISA and folate levels were assayed by
electrochemiluminescene immunoassay, in addition MTHFR C677T gene
polymorphism was evaluated using PCR and restriction fragment length
polymorphism (RFLP) using HinfI restriction enzyme. Both NT-proBNP and Hcy
were significantly increased but folate was significantly decreased in the patients
groups as compared to the control subjects. Both Hcy and NT-proBNP were
significantly positively correlated with depression scores assessed by Hamilton
Rating Scale of Depression (HRSD), but significantly negatively correlated with
cognitive impairment assessed by Mini-mental state examination (MMSE) score. The
carriers of MTHFR, TT genotypes had an increased risk of developing depression
and had significantly higher plasma level of both and NT-proBNP and Hcy than CT
or CC patients genotypes (p<0.001).
In conclusion: the MTHFR C677T gene variation may play an important role in the
modulation of mood but does not contribute to genetic susceptibility to cognitive
performance in later life. The MTHFR C677T mutation is associated with plasma Hcy
and NT-proBNP levels. Elevated NT-proBNP and Hcy levels may play a role in
link ing depression and /or MCI with increased cerebrovascular and/or cardio-vascular risk .