Limited, Encouraging Support for Choline in Alzheimer's

This is the final post in which randomized, clinical trials of the potentially active ingredients in the branded drink Souvenaid are reviewed. (For background on Souvenaid's development, go here, here, here, and here.) 

The remaining components to be examined in the nutritional supplement are phospholipids, choline, and uridine monophosphate (UMP).

In the case of UMP, a directed PubMed search reveals no randomized, controlled trial of the RNA nucleotide in Alzheimer disease. Therefore the rationale for assessing UMP in cognitive dysfunction appears to extend solely from animal studies (for instance, see a 2008 rat study by anchor author Wurtman, who is also coauthor of the recently published Souvenaid study).

The rationales for giving phospholipids or choline to AD patients are either 1) to bolster the integrity of neuronal membranes by providing the necessary building blocks, or b) in the case of choline, to supply a precursor for the neurotransmitter acetylcholine, which is deficient in AD. 

Barring the negative studies of lecithin,* a potential source of both phospholipids and choline, there are at least 9 randomized, controlled trials (published from 1986 to 2003) of these substances in dementia. Six studies, from the 80s and 90s, assessed the specific phospholipid phosphatidylserine; 3 studies assessed choline alfoscerate or citicoline. Most of these studies enrolled outpatients with mild-to-moderate AD. General study features are tabulated here:

Intervention	N	Duration	Outcome in a Nutshell
Phosphatidylserine
1986	42	6 wk	Trend toward improvement or significantly improved
1986	No abstract	—	—
1992	51	3 mo	Improvement observed in milder disease
1992	33	2 mo	Mixed improvement
1992**	40	6 mo	PET-correlated cognitive improvement
1994**	70	6 mo	Temporary improvement
Acetylcholine precursors
1993	126	?	Significant improvements with choline alfoscerate
1999	30	3 mo	Citicoline associated with improvements in APOE ε4 carriers; effect more pronounced in mild disease and associated with physiologic changes
2003	261	6 mo	Choline alfoscerate improved cognition or delayed cognitive decline

Cumulative data from the relatively small, controlled studies of phosphatidylserine in AD suggest that whatever cognitive improvements exist, they are short lived.

The most compelling support for the use of choline (ie, choline alfoscerate) comes from a sizeable, randomized, placebo-controlled, 6-month study performed at the Instituto Nacional de la Senectud in Mexico City. Cognitive assessments, performed with the ADAS-cog and other well-recognized tests, showed either a significant delay in cognitive decline or actual cognitive improvement. 

Nevertheless, these impressive results must be replicated. 

ADAS-cog = Alzheimer's Disease Assessment Scale, cognitive subscale; PET = positron emission tomography.

* A directed PubMed search reveals at least 5 studies of lecithin in AD, published from 1981 to 1987. Among the 3 small placebo-controlled studies in which an abstract is provided, none showed clinical improvement with supplementation (treatment duration, from 10 weeks to 6 months), despite a rise in plasma choline levels. These search results omit at least 8 trials of the defunct cholinesterase inhibitor tacrine, in which lecithin was provided as standard treatment.

** Treatment options were phosphatidylserine or pyritinol, a vitamin B6 analog.

Photograph of atrophied brain from person with AD: National Institute on Alcohol Abuse and Alcoholism.