Brew on this: Latest research on coffee's connection to Alzheimer's
By Denise A. Valenti

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As I stared into my morning cup of black coffee, trying to percolate into alertness, I received an email from a colleague alerting me to a recently published article about acetylcholinesterase inhibition. Some of the most commonly prescribed medications for Alzheimer's disease act upon the cholinergic system, inhibiting acetylcholinesterase.

Apparently, I was dosing myself to jump-start the neuroprocessing in my brain at that very moment. The publication my colleague was appraising me of — Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase — is important research in understanding how dietary substances impact disease expression and progression.

Acetylcholinesterase (AChE) can interfere with the activity of the neurotransmitters — acetylcholine, epinephrine, norepinephrine and serotonin. Neurotransmission is stopped by AChE. By inhibiting the activity of AChE, there is an increase in neurotransmission.

Drugs that inhibit AChE or acetylcholinesterase inhibitors (AChEIs) are standard treatments for Alzheimer's disease. Two such drug therapies were used as standard for the study of caffeine: donepezil (Aricept) and tacrine (Cognex). The activity of AChE on the termination neurotransmission is fairly well understood; that of buyrylcholinesterase (BChE) is not.

The two standards to which caffeine was compared act on two different types of AChE; donepezil acts on what are called muscarinic receptors, and tacrine on those referred to as nicotinic. AChEIs impact other structures; but this is poorly understood. AChEIs have also been shown to affect ocular structures to lower eye pressure, provide retinal neuroprotection and contribute to cataracts.

A large study in Sweden looked at 7,073 registrants with a diagnosis of Alzheimer's disease or Alzheimer's with mixed dementia. After a follow-up of more than two years, it was found that those who took the highest dose of AChEIs (donepezil, rivastigmine or glanatamine) had the lowest risk of myocardial infarcts or death compared to those that had never used AChEIs. The associations of reduced incidence were stronger with an increasing AChEI dose.

In a study assessing blood plasma levels of caffeine/biomarker in 124 participants with mild cognitive impairment, researchers found that the caffeine biomarker predicted changes in cognitive status over a two-to-four-year period. They concluded caffeine/coffee intake can be associated with a reduced risk of dementia or delayed onset in those already diagnosed with mild cognitive impairment.

Mouse models of Alzheimer's disease have demonstrated that crude caffeine, the byproduct of decaffeination, reduces amyloid plaque deposits in the mice. Amyloid deposits are part of the Alzheimer's disease in humans. In another mouse study using chronic regular consumption of coffee, the coffee slowed down progression of dementia.

The researchers found the mice "maintained their locomotor habituation ... maintained their exploratory drive ... In addition, morphometric analysis of hippocampal neurons revealed that dendritic branching ... total dendritic length, and spine density in distal dendritic branches ... the present findings strengthen the epidemiological observations suggesting that prolonged caffeine intake prevents the cognitive decline associated with aging, and open the possibility that this process could be mediated by promoting the growth of dendrites and spines in neurons of the adult mammalian brain."

Not sure what to make of all this, so I guess I will just have another dose of caffeine while I sort it all out.

Dr. Denise A. Valenti is a residency-trained, low-vision/blind-rehabilitation optometrist with additional education and expertise in the field of age-related neurodegenerative diseases with the emphasis on Parkinson's disease and Alzheimer's disease. Her research has included the study of imaging of retinal neural tissue using Optical Coherence Tomography and functional assessment of neural processing in the visual system using Frequency Doubling Technology. Dr. Valenti provided direct clinical care for more than 25 years and currently is active in research and consultation related to vision, aging, neuroprocessing and cognitive functions.