Differential Pharmacological Effects on Brain Reactivity and Plasticity in Alzheimer’s Disease

Abstract

Acetylcholinesterase inhibitors (AChEIs) are the most commonly prescribed monotherapeutic medications for Alzheimer’s disease (AD). However, their underlying neurophysiological effects remain largely unknown. We investigated the effects of monotherapy (AChEI) and combination therapy (AChEI and memantine) on brain reactivity and plasticity. Patients treated with monotherapy (AChEI) (N = 7) were compared to patients receiving combination therapy (COM) (N = 9) and a group of age-matched, healthy controls (HCs) (N = 13). Cortical reactivity and plasticity of the motor cortex were examined using transcranial magnetic stimulation. Cognitive functions were assessed with the cognitive subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), activities of daily living (ADLs) with the ADCS-ADL. In addition we assessed the degree of brain atrophy by measuring brain-scalp distances in seven different brain areas. Patient groups differed in resting motor threshold and brain atrophy, with COM showing a lower motor threshold but less atrophy than AChEI. COM showed similar plasticity effects as the HC group, while plasticity was reduced in AChEI. Long-interval intracortical inhibition (LICI) was impaired in both patient groups when compared to HC. ADAS-Cog scores were positively correlated with LICI measures and with brain atrophy, specifically in the left inferior parietal cortex. AD patients treated with mono- or combination-therapy show distinct neurophysiological patterns. Further studies should investigate whether these measures might serve as biomarkers of treatment response and whether they could guide other therapeutic interventions.

Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer’s Disease

“…normal subjects, which might have played a role for some patients. And in an own study, we found that pharmacological treatment can also have a specific impact on plasticity measures in AD (Brem et al, 2013). We also found reduced SICI and LICI in AD patients, which were associated to baseline ADAS-Cog.…”

Reproducibility of Single-Pulse, Paired-Pulse, and Intermittent Theta-Burst TMS Measures in Healthy Aging, Type-2 Diabetes, and Alzheimer’s Disease

“…Some factors could be disease-specific, such as fluctuations in blood glucose levels in T2DM, though, importantly, glucose levels (within the range of 80–200 mg/dL, specified a priori ) were not found to influence variability in the present study. Interestingly, the AD group showed numerically higher reproducibility coefficients for nearly all measures, including RMT, SICI and iTBS aftereffects, which several studies in AD have shown to be abnormal and/or predictive of disease severity or response to treatment ( Liepert et al, 2001 ; Di Lazzaro et al, 2004 ; Koch et al, 2012 , 2015 ; Brem et al, 2013 ; Balla et al, 2014 ). It is possible, however unlikely, that some aspect of the Sham treatment (e.g., daily study visits or interaction with study staff) that the AD group underwent had some stabilizing effect on their neurophysiology.…”

Transcranial Magnetic Stimulation for the Assessment of Neurodegenerative Disease

“…The reduction of SICI has been an inconsistent finding, with a number of studies reporting a normal level of SICI [174][175][176][177][178]. One study reported a reduction of LICI in AD, which appeared to be correlated with cognitive deficits [179]. Separately, consistent reduction of SAI has been established in AD [6,43,180], in keeping with dysfunction of the cholinergic system.…”