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VEP P2 latency in Alzheimers linked to cholinergic mechanisms!!!

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Most studies of the flash visual evoked potential (VEP) in Alzheimer’s disease find that, compared to groups of age-appropriate controls, groups of Alzheimer’s disease subjects manifest a delayed P2 component.

Both the flash P1 and the pattern reversal P100 have long been known to be generated by the sparsely cholinergic primary visual cortex which remains relatively intact in Alzheimer’s disease. The flash P2, by contrast, derives from the richly cholinergic circumstriate visual association cortex, which undergoes marked progressive deterioration in this disease. Groups of patients whose dementias stem from etiologies other than Alzheimer’s disease generally do not show the selective P2 delay.However, among Alzheimer’s disease patients the delay increases over time in parallel with the severity of dementia symptoms and among healthy subjects it can be produced de novo by cholinergic suppression. More importantly, the selective P2 delay has been reported to be pathognomonic for Alzheimer’s disease and several authors have called for its evaluation as a diagnostic tool. Such an evaluation has recently been completed. P2 data recorded from Alzheimer’s disease patients and healthy subjects were analyzed using several techniques, yielding very significant between-group differences, but individual diagnostic accuracies of only 62% (sensitivity 80%; specificity 53%; ROC area 0.659) to 68% (sensitivity 60%; specificity 75%; ROC area 0.694). These were felt to be too low to add meaningful information to the McKhann diagnostic process or to substitute for the complete diagnostic workup. However, it must be noted that the stimulation, measurement, and analytical techniques used were deliberately restricted to the brightest flash, the simplest latency measures and univariate data analyses in order to be suitable for wide application in clinical laboratories. A follow-up study to find the optimal stimulus and recording parameters for

the P2 has been completed recently, but additional research is badly needed to identify the analytical technique yielding the best discrimination between individual subjects. Only then will it be known whether the robust between-group differences can be translated into clinically useful between-subject differences. The P300 ERP and P2 EP components have not yet generated the evidence base necessary to be included among clinically applicable procedures, though the goal of a positive laboratory test for dementia in general (P300) or Alzheimer’s disease in particular (P2) continues to motivate research.

source: Applied Neuroscience[PDF]

So.. Let's see what we can grasp from this. A delayed P2 component can be produced by cholinergic suppression. For the time being, I do not know whether a delayed P2 component is an interchangable term with shortened P2 latency.

But IF it is, then this shows us a remarkable new approach to improving the sensory gating deficits characterizing HPPD (read: Improve HPPD symptoms). Thinking back to my findings on Coluracetam.... Coluracetam's cholinergic mechanism is that of a Choline Reuptake Enhancer, unique in its kind. It is not strange then to find that Coluracetam has been reported to have such profound on visual acuity. I find this highly exciting. If you're interested, there are many referances in the link provided above.

Also, you can have a look at my findings on Coluracetam. Later I'll be adding my findings on Aniracetam, which has shown to improve visual hallucinations in Parkinson's patients among others.

Please feel free to add your thoughts on any of this.

Update: additional information.


This study has shown that administration of a low dose of an anticholinergic agent to normal subjects also produced an increase in the flash P2 and N3

latency. The effect was small owing to the very low dose used, but was significant enough to suggest that the larger flash P2 delays seen in Alzheimer's disease could be explained by the large reductions in cholinergic activity associated with this disease. The increase in the flash N2-P2 amplitude produced by the hyoscine in this study is also found in patients with presenile dementia. However, our previous study indicated that it is the latency rather than the amplitude effect which is specific to dementia.

source: Changes in the human visual evoked potential caused by the anticholinergic agent hyoscine hydrobromide: comparison with results in Alzheimer's disease [PDF]

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system.

Coluracetam enhances high-affinity choline uptake (HACU) which is the rate-limiting step of acetylcholine (ACh) synthesis, and is the only known choline uptake enhancer to currently exist. Studies have shown Coluracetam to improve learning impairment on a single oral dose given to rats which have been exposed to cholinergic neurotoxins. Subsequent studies have shown that it may induce long-lasting procognitive effects by changing the choline transporter regulation system.[6]


Both from wikipedia.


The results indicate that an acetylcholine deficit produces a delay to the flash P2 component of the visual evoked potential. No change was detected when other stimuli were used.


Whether or not my theory above is accurate, it doesn't really matter. If a delay in P2 means a lengthened latency, then perhaps one could coordinate research to cover acetylcholine excess. And even if it doesn't mean the latency, then either way the acetylcholine link is well worth time spent studying for future hypotheses.

Update: Finally something to expand on the comprehension of VEP's.


The main parameters measured with the VEP are its amplitude and latency, the latter being more informative. VEP amplitude is quite variable in persons with normal vision. Latency of the transient VEP is most commonly assesed using the time delay from the stimulus presentation to the P1 (or P100) peak of the VEP waveform, a large positive potential that, in persons with normal vision, occurs around 100 ms after stimulus presentation. The VEP may be employed to detect or analyze various disorders of the anterior afferent visual pathway. By understanding the mechanisms of damage, some of the abnormalities in the VEP can be predicted. In anterior ischemic optic neuropathy, for example, the VEP is frequently low in amplitude but normal in latency. On the other hand, delayed VEP responses are characteristic in demyelination of the optic nerve secondary to optic neuritis or compression. The lack of specificity in VEP abnormalities, however, is a major drawback in clinical assessment. Latency delays occur not only in demyelination, but als in neurotransmitter disorders, glaucoma, with uncorrected refractive error, with media opacities and in normal human aging.

source: Neuro-opthamology page 46 (google ebook link)

From the bolded sentence, we can conclude that a delayed VEP directly correlates to latency.

Thus the question is: Is a delayed VEP response a shortened latency?

Delayed means it takes longer time to process. Latency (from wiki) is a measure of time delay.

If a shortened latency means that it takes less time to process, then a delayed VEP would mean the opposite.

And then one could conclude that acetylcholine deficits produce a lengthened latency...

And thus one could think that excess acetylcholine might produce a shortened latency...

Ultimately arriving to the conclusion that a acetylcholine inhibitor might improve the shortened latency in HPPD..

It just seems to inconcrete to think of it that way. It would make so much more sense that an acetylcholine deficit causes shortened latency, and acetylcholine enhancement would mitigate that. But I could be very off either of these conjectures.

Aaaargh! Admittedly my English isn't the best, combine this with my cognition.

Any help on this would be greatly appreciated!!!

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