Cholinesterase inhibitors affect brain potentials in amnestic mild cognitive impairment

Abstract

Amnestic mild cognitive impairment (MCI) is an isolated episodic memory disorder that hasa high likelihood of progressing to Alzheimer's disease. Auditory sensory cortical responses (P50, N100) have been shown to be increased in amplitude in MCI compared to older controls. We tested whether (1) cortical potentials to other sensory modalities (somatosensory and visual) were also affected in MCI and (2) cholinesterase inhibitors (ChEIs), one of the therapies used in this disorder, modulated sensory cortical potentials in MCI. Somatosensory cortical potentials to median nerve stimulation and visual cortical potentials to reversing checkerboard stimulation were recorded from 15 older controls and 15 amnestic MCI subjects (single domain). Results were analyzed as a function of diagnosis (Control, MCI) and ChEIs treatment (Treated MCI, Untreated MCI). Somatosensory and visual potentials did not differ significantly in amplitude in MCI subjects compared to controls.When ChEIs use was considered, somatosensory potentials (N20, P50) but not visual potentials (N70, P100, N150) were of larger amplitude in untreated MCI subjects compared to treated MCI subjects. Three individual MCI subjects showed increased N20 amplitude while off ChEIs compared to while on ChEIs. An enhancement of N20 somatosensory cortical activity occurs in amnestic single-domain MCI and is sensitive to modulation by ChEIs. IntroductionMild cognitive impairment (MCI) describes older individuals having cognitive impairments without accompanying functional impairments that characterize dementia (Petersen et al., 1999). Recent studies have suggested criteria for distinguishing among four subtypes of MCI based on the presence of both episodic memory impairment (amnestic or non-amnestic MCI) and other cognitive impairments (single-or multipledomain MCI) (Petersen, 2004). For example, amnestic singledomain MCI refers to patients with involvement of only memory deficit whereas amnestic multiple-domain MCI refers to patients with impairment of both memory and other cognitive domains such as language or executive function. MCI subjects have a high risk of converting to Alzheimer's disease Petersen et al., 1999) and show neuropathological features of β-amyloid plaques and neurofibrillary tangles similar to early Alzheimer's disease (Kordower et al., 2001;Mufson et al., 1999). These findings suggest that MCI can be a precursor of Alzheimer's disease. Cholinergic processes in neocortical areas are affected in Alzheimer's disease (Geula and Mesulam, 1989;Heckers et al., 1992) and are particularly apparent late in the course of

The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion

“…Also, we have examined amplitude changes in this work rather than latency shifting. Some research has been done on cholinesterase modifying drugs regarding early somatosensory and visual ERPs in MCI subjects and found drugs effects concerning very early somatosensory ERPs (N20, P50) but no effects on early visual ERPs (N70, P100, N150) [40]. Our result concurs that later post-stimulus ERPs (visual and cognitive processing) do not seem to be affected by cholinesterase treatments to the extent of altering ERP assessment of clinical status.…”

Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease – a two‐case study

“…The enhanced P50 response is well described in patients with AD and MCI (Green et al ., ). Another study compared amnestic MCI patients treated with cholinesterase inhibitors to untreated patients and found larger P50 amplitudes in untreated patients with MCI (Irimajiri et al ., ). Another interesting study compared the brain responses of healthy subjects with and without AD relatives (Boutros et al ., ).…”

Cognitive Event-Related Potentials: Biomarkers of Synaptic Dysfunction Across the Stages of Alzheimer's Disease

“…P50 amplitude predicted progression from MCI to AD, and differentiated amnestic MCI subtype from MCI with other cognitive impairments beyond memory deficit [96, 97]. Several studies have found N200 and P300 abnormalities in MCI, with some results suggesting that amplitude or latency of N200 may have stronger value in discriminating MCI patients from normal control [98–100].…”