Towards more rational prescribing of anti-dementia drugs

To the Editor

A 69 year old man presented to our regional memory clinic with gradual decline in short term memory over nine months. He had anomia of familiar people, word finding difficulties, and lacked motivation to keep in touch with his children. Although more lethargic, he was still independent with all activities of daily living. There were no concerns with his driving, nutrition, continence, mobility, or mood. He scored 27/30 in the mini-mental state examination (MMSE), and 9/18 in the frontal assessment battery (FAB). Physical examination revealed bilateral palmomental reflexes, more significant decline in encoding than retrieval, and paucity of speech which was almost stuttering. The rest of his examination and routine bloods work-up were unremarkable. His CT brain showed frontal atrophy only.

Upon his request and consent, 5mg rivastigmine patch daily was trialled for three weeks. At three weeks he reported increased frequency in bowel habits and urination, but cognition and function did not improve at all. Given the predominant frontal features and poor response to rivastigmine, there was a high index of suspicion of underlying frontotemporal dementia (FTD). Although there are conflicting reports about memantine use in FTD, and memantine is only approved for moderate to severe Alzheimer’s disease (AD), he was more alert and assertive after trialling memantine, which pleased him and his wife. Repeat MMSE and FAB scores improved to 28/30 and 14/18 respectively. Memantine has been shown to increase metabolism in the salience network in FTD (Chow et al., 2011), a network associated with social emotional function and hypometabolism in FTD.

There is consensus that early diagnosis and management of dementia improve quality of life, which delays residential care placement, and so is very cost effective. Anti-dementia drugs (ADD) like acteylcholinesterase inhibitors (AChEI) and memantine are not disease modifying therapies, but they do improve quality of life in some AD cases. AChEI also has benefit in Lewy body dementia sufferers (McKeith et al., 2005). However subsidies for ADD use in Australia are approved only in AD sufferers, based on MMSE cut-off scores.

Dementia neuropathologies may have different local and distant topographical effects cerebrally (La Joie et al., 2012). Hence cognitive screening cut-off scores, which have not been validated by gold standard histopathological diagnoses, are less important than deficit patterns on scores in determining underlying neuropathology, which may better guide management, like in this patient. Finally initial prescriptions of ADD could be worth considering when potential benefits might outweigh the risk, even if off label or an out of pocket fee applies.