Beyond Dopamine – Does PD Effect Other Neurotransmitters?

Trends in PD research are showing that in addition to Parkinson’s impact on the neurotransmitter dopamine and the dopamingeric system, the neurotransmitter acetylcholine and the brain’s cholingeric system are also impacted.

This post reviews recent research (and some very old research that may need to be revisited), and discusses how two vitamins/supplements (Vitamin B12 and Citicoline/CDP Choline) may impact Parkinson’s disease. This should not be considered medical advice. Always consult your doctors and pharmacist about any vitamins or supplements that you are taking or considering.


Exhibit A: Yale Study challenges assumptions about PD and acetylcholine

Several weeks ago, a Yale study challenged a long held assumption about Parkinson’s effect on a neurotransmitter other than dopamine. The loss of dopamine leads to slower movements, resting tremors, and other symptoms that worsen over time. To help these symptoms, doctors prescribe treatments that increase dopamine levels in the striatum, a portion of the brain that is responsible for motor learning. However, medical treatments do not consider the effects of Parkinson’s on another neurotransmitter, acetylcholine.

Scientists had previously believed that when dopamine levels dropped, acetylcholine levels increased, or at best stayed the same. Concerns were raised about the ratio of dopamine to acetylcholine, but this relationship had never been thoroughly investigated, despite acetylcholine’s likely role in creating a movement disorder called dyskinesia (according to the Yale research), which develops in most patients after several years of dopamine treatment for Parkinson’s.

The Yale research argues that dopamine deficiency reduces acetylcholine, and suggests that treating Parkinson’s may require targeted therapies that restore the balance between these two chemicals, instead of focusing solely on dopamine, said the researchers.

More on this Yale study:

Exhibit B: Mayo research commentary on Vitamin B-12

Earlier this year, a research commentary from Mayo Clinic analyzed the relationship between low levels of Vitamin B-12 and Parkinson’s Disease. Of particular concern is that low B-12 levels in early stages of PD are a good predictor of a greater worsening of mobility as PD progresses. Note that these “lower” vitamin B12 are still in the normal reference range for B12 tests, and even patients with “normal” vitamin B12 levels have faster motor progression if in the low-normal quartile.

We highlighted some of the most significant bits of information from this recent Mayo Clinic research commentary, and included their video and a link to the full commentary here:

For the purposes of this current discussion, note that this Mayo research commentary goes into great detail on cholinergic dysfunction in PD, proposing “that vitamin B12 supplementation could be considered as an adjuvant approach to improve cholinergic transmission and, potentially, motor and cognitive function in patients with PD.” In other words, the main theory of why B12 may help PD is by boosting acetylcholine.

Cholinergic dysfunction is suspected of being more of an issue with gait (walking) and balance (falls), as well as postural sway and dyskinesia. The Mayo B12 commentary has a fascinating references list of studies that have analyzed acetylcholine’s role in these PD symptoms.

Dopamine deficiency seems to be behind slowness of movement, tremor, and freezing. However, researchers are suspecting acetylcholine play a role in gait disturbances, balance, walking, postural sway and dyskinesia.

Exhibit C: Anticholingeric drugs may help a few, but they seem to be linked to dementia.

From a pharmaceutical perspective, most of the drug development related to acetylcholine has focused on suppressing it, with so called anticholingeric drugs. As mentioned in Exhibit A, historically it was assumed that there was an imbalance between dopamine and acetylcholine, but it was assumed that acetylcholine was increased in proportion to dopamine.

This category of drugs is not very widely prescribed for people with PD. The primary PD drug in this category is Artane/Trihexyphenidyl. For some people, this drug, added with other PD drugs, can be beneficial in helping to reduce tremor. But, numerous studies show a correlation of higher rates of dementia among people taking these drugs.

This CBS News report provides a good overview of the research concerns:

Exhibit D: A Finnish study reports that increased dietary choline is associated with a reduced risk of dementia.

A study in Finland observed that diets that were higher in choline were associated with a reduced risk of dementia. Choline is an essential nutrient, usually occurring in food. Choline is also necessary for the formation of acetylcholine, the other neurotransmitter that we have been discussing. The key sources of phosphatidylcholine in this particular study population’s diet were eggs and meat.

Question: Does boosting acetylcholine, in conjunction with conventional levodopa dopamine boosting therapy make sense?

Suppressing acetylcholine (Exhibit C) seems to be linked to dementia (bad for the brain), while this latest Finnish review study (Exhibit D) suggests that increased consumption of choline (an acetylcholine precursor) may reduce the risk of dementia (good for the brain).

Which brings us back to the Yale research report (Exhibit A) which challenged long held assumptions about acetylcholine and dopamine in PD. The common assumption has been that while dopamine was obviously decreased in PD, acetylcholine was increased. Yale researchers argue both dopamine and acetylcholine are decreased.

Does boosting acetylcholine, in conjunction with conventional levodopa dopamine boosting therapy make sense?

I’m neither a doctor nor research scientist, and completely unqualified to make an analysis in this area. But there was a research study almost 30 years ago that may have done this without realizing it was doing so.

Exhibit E (and Wrap-up): CDP Choline (Citicoline) and PD Study from 1990

For years I have been intrigued by a small study of 85 patients from way back in 1990, where half had their levodopa dosage reduced in half while supplemented with CDP Choline (Citicoline), yet fared as well or better than those who continued their regular levodopa dosage.


Full text from the above study:

At the time, the researchers assumed that CDP Choline must help boost dopamine levels, because the PD patients were able to lower their dosage of levodopa. But considering that CDP Choline is an acetylcholine precursor, might the actual benefit of this therapy have been that they were boosting both dopamine and acetylcholine at the same time?

I’m not suggesting that this is a magic pill, and the results of a small study that is almost 30 years old is insufficient evidence to warrant adding an unproven supplement to your diet. But, for some, this may be worth a further discussion with their doctors about whether CDP Choline supplementation might be worth investigation.

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