Article Details

2017 | October-December | Issue4
Cognitive Decline due to Impaired Homocysteine Metabolism in Adults on Antiepileptic Monotherapy: A Prospective Study
Namrata Khanna, Vandana Tiwari, Dinkar Kulshrestha, Manish Raj Kulshrestha, Pradeep Kumar Maurya, Sajjan Lal Verma, Ajai Kumar Singh, Anup Kumar Thacker


Aim: Long-term antiepileptic therapy is associated with hyperhomocysteinemia (HHcy), causing cardiovascular risk and subsequent cerebrovascular and cognitive disorders. Objective of our study is to assess the effects of old and new generation drugs on homocysteine (Hcy), folate, and B12 levels in serum and to relate HHcy with cognitive decline.

Materials and methods: Drug-naive patients recently diagnosed with epilepsy in the age group 18 to 40 years (n = 124) were recruited and grouped according to the drug prescribed: conventional drugs, like phenytoin, carbamazepine, valproate, and newer drugs, like oxcarbazepine and levetiracetam. A pretreatment analysis of Hcy, folate, and B12 was done. Mini- Mental State Examination (MMSE) was used to assess cognitive impairment, if any. After 6 months of continuous monotherapy, the analyses were repeated.

Results: Homocysteine levels were raised significantly in all the groups (p < 0.05 in all groups) after 6 months of therapy. Hyperhomocysteinemia (>15.1 μmoles/L) was found in 64 out of 124 patients, of which 42 were on conventional drugs. Folate and B12 registered a significant decrease in patients on phenytoin, carbamazepine, and oxcarbazepine. Cognitive decline was evaluated as drop of a point or more in MMSE score after 6 months of therapy. A significant positive relation between Hcy and cognitive decline was seen in groups on monotherapy of phenytoin [relative risk (RR) = 4.667; confidence interval (CI) = 0.7663, 28.42], carbamazepine (RR = 2.778; CI = 1.042, 7.403), and oxcarbazepine (RR = 3.316; CI = 0.9483, 11.59). An insignificant positive correlation was observed in sodium valproate and levetiracetam groups.

Conclusion: Both conventional and newer antiepileptic drugs (AEDs) may cause HHcy, leading to cardiovascular complications and cognitive decline. Subjects on sodium valproate and levetiracetam are less likely to show a decline in cognition, regardless of a rise in Hcy levels.

Clinical significance: Folate and B12 deficiency causes HHcy, which correlates positively with cognitive decline.

Keywords: Antiepileptic drugs, Cognitive decline, Hepatic enzyme inducers, Mini-Mental State Examination.

How to cite this article: Khanna N, Tiwari V, Kulshrestha D, Kulshrestha MR, Maurya PK, Verma SL, Singh AK, Thacker AK. Cognitive Decline due to Impaired Homocysteine Metabolism in Adults on Antiepileptic Monotherapy: A Prospective Study. MGM J Med Sci 2017;4(4):171-176.

Source of support: Nil

Conflict of interest: None

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