Cognition Symptoms: Huntington's impairs "thinking" skills that are mostly related to the ability to plan and organize thoughts. There is particular difficulty with "multitasking" or shifting frames of thought. Memory is less affected.

Cognition Treatments: There are studies in HD mice models showing that environmental enrichment [Hockly 2002] and voluntary exercise give significant cognitive benefit. Cognitive benefit of fluoxetine (Prozac®) has also been reported in mice [Grote 2005].

Studies in Parkinson's have shown that anticholinesterase drugs originally approved for use in Alzheimer's give cognitive benefits in this disease [Maidment 2006]. However two small trials in Huntington's have given variable results. Rivastigmine (Exelon®) appeared to give small benefit [de Tommaso 2007] while donazepil (Aricept®) did not [Cubo 2006].

There are presently small ongoing trials in Huntington's testing three separate drugs for cognition benefit. These include citalopram (Celexa®), atomoxitine (Strattera®), and memantine (Namenda®). At least theoretically, these drugs have greater likelihood of benefit than anticholinesterase drugs.

Commonly Used Cognition Medications

Memantine (Namenda®) This drug works by blocking glutamate action. Dosing starts at 5 mg/day for the first week, then increases by 5mg/day for the next 3 weeks (wait a week to increase each dose).  The target dose is 20-30 mg/day in divided doses twice daily.  Side effects include dizziness, headache, constipation, high blood pressure.

Rivastigmine (Exelon®) This drug is a cholinesterase inhibitor that is used in both Alzheimer's and Parkinson's.  Dosing starts at 1.5 mg twice daily, doubling the dose every two weeks till reaching a maximum of 6 mg twice daily.  Side effects include nausea, and stomach distress, diarrhea and fatigue.It should be taken with meals to decrease stomach upset.

Donepezil (Aricept®) This is a cholinesterase inhibitor.  Dosing starts at 5 mg once daily.  This dose can be increased to 10 mg/day after a wait of 3 weeks.   It is best taken at bedtime to decrease side effects which include headache, diarrhea, fatigue, loss of appetite, dizziness, and fatigue.

References

Hockly E, Cordery PM, Woodman B, Mahal A, van Dellen A, Blakemore C, Lewis CM, Hannan AJ, Bates GP. Environmental enrichment slows disease progression in R6/2 Huntington's disease mice. Ann Neurol 2002 Feb;51(2):235-42. PubMed abstract

Grote HE, Bull ND, Howard ML, van Dellen A, Blakemore C, Bartlett PF, Hannan AJ. Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine. Eur J Neurosci 2005 Oct;22(8):2081-8. PubMed abstract

Maidment I, Fox C, Boustani M. Cholinesterase inhibitors for Parkinson's disease dementia. Cochrane Database Syst Rev 2006;(1):CD004747. PubMed abstract

de Tommaso M, Difruscolo O, Sciruicchio V, Specchio N, Livrea P. Two years' follow-up of rivastigmine treatment in Huntington disease. Clin Neuropharmacol 2007;30(1):43-6. PubMed abstract

Cubo E, Shannon KM, Tracy D, Jaglin JA, Bernard BA, Wuu J, Leurgans SE. Effect of donepezil on motor and cognitive function in Huntington disease. Neurology 2006 Oct 10;67(7):1268-71. PubMed abstract