Acute Nicotine Administration in Alzheimer’s Disease: An Exploratory EEG Study

Abstract

Previous findings of cognitive deficits and EEG slowing in Alheimer’s patients, together with independent reports of the performance enhancing and electrocortical activating properties of nicotine in normal adults, stimulated this study to examine the acute effects of nicotine on spectrum-analyzed EEG in patients with dementia of the Alzheimer type (DAT). Thirteen patients, 6 currently receiving cholinesterase inhibitor treatment and the remaining being medication free, were administered 2 mg of nicotine polacrilex under randomized, placebo-controlled conditions. Compared to age-regressed EEG norms, the pretreatment EEG spectrums of patients in general were characterized by excessive slow (delta and theta)-wave power, diminished fast (alpha and beta)-wave power and slow mean alpha and total band frequencies. Although postnicotine EEG indices remained within the abnormal range, nicotine, compared to placebo, significantly shifted EEG towards normal values by reducing slow wave (relative delta and theta) power and augmenting fast (relative alpha-1, alpha-2, beta-1) wave power. No differences were observed between treated and nontreated patients in response to nicotine. The results are discussed in relation to cholinergic and brain arousal systems and their relationship to cognitive processes.

Effects of Strain, Behavior and Age on the Self-Administration of Ethanol, Nicotine, Cocaine and Morphine by Two Rat Strains

“…This assumption is bolstered by data from this laboratory [30], which showed that the amount of cocaine-induced dopamine release in the shell of the nucleus accumbens correlated highly with the voluntary oral intake of cocaine in the same animal. Also, an oral dose of only 2 mg of nicotine (2 mg/70 kg or 0.03 mg/kg) in human volunteers produced significant EEG changes [27] indicating that the higher doses consumed voluntarily by our animals most likely also produce a pharmacological effect.…”

Cholinergic receptor subtypes and their role in cognition, emotion, and vigilance control: An overview of preclinical and clinical findings

“…Foulds et al (1994) studied the effect of subcutaneous nicotine injections in non-smokers and found an increase in alpha frequency. Nicotine administered to Alzheimer's disease patients brought about a shift of EEG measures towards normal values, specifically a reduction of relative delta and theta power and an increase in relative alpha-1, alpha-2 and beta power (Knott et al 2000).…”

Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers

“…Of primary interest, cognitive decline in Alzheimer's patients was found to correlate with EEG slowing (Prichep et al 1994;Forstl et al 1996;Besthorn et al 1997;Rodriguez et al 2002;Kowalski et al 2001;Moretti et al 2004 for review), which was reversed by short-term treatment with acetylcholinesterase inhibitors (Jelic et al 1998;Brassen and Adler 2003). Interestingly, in healthy volunteers, nicotine decreased slow wave activity and increased fast wave activity (Foulds et al 1994;Knott et al 1999;Lindgren et al 1999), effects which are opposite to those observed in AD (Knott et al 2000). The validated CDR computerized test battery was used for assessment of changes in attention, learning, and memory, as this system has proven sensitive to drug-induced cognitive changes in healthy subjects, including physostigmine, which belongs to the same class of compounds as those currently used to treat Alzheimer's disease (Wesnes et al 1994).…”