Psychometric Discrimination of Tetrahydroaminoacridine Responders in Alzheimer Patients

Abstract

Fourteen patients with probable Alzheimer''s disease (AD) participated in an open tetrahydroaminoacridine (THA) treatment trial. Before initiation of THA treatment, a brief battery of neuropsychological tests was performed by an experienced neuropsychologist. The tests were repeated 120 min after a single dose of 50 mg THA had been administered perorally. Thereafter, the patients had a 4-week active treatment with THA 100 mg/day. After the treatment period, eight patients were defined as responders (increase of Mini-Mental State Examination score ≧ 3) and six patients as nonresponders to the treatment. The responders showed significant improvement on Digit Span, Trail Making B, and on both Clock Setting and Clock Recognition tests after 50 mg of THA. The results suggest that in this subgroup of AD patients augmentation of the brain cholinergic systems mainly led to improvement of attentional and frontal-lobe rather than mnemonic functions.

Responder Characteristics to a Single Oral Dose of Cholinesterase Inhibitor: A Double-Blind Placebo-Controlled Study withTacrine in Alzheimer P atients

“…Subcutaneous administration of nicotine to AD patients produced improvement in attentional functions [64]. A similar effect that attention was improved was observed in this study following a single dose of tacrine as well as in an earlier study [7]. Animals with cholinergic lesions of the basal forebrain show attentional deficits [65], and the prefrontal cortex appeared to be involved in these mechanisms [66].…”

“…An improvement in EEG activity with an increase in mean frequency and a decrease in slow frequency [7][8][9][10] have been observed following long-term treatment with tacrine in AD patients. Similarly, increases in brain glucose metabolism [11][12][13] as well as cerebral blood flow [14] have been measured by positron emission tomography (PET) following tacrine treatment.…”

“…A limiting factor for tacrine treatment has been the side effects occuring in a relatively large proportion of patients [7]. The reasons for withdrawal have mainly been due to gastrointestinal symptoms (e.g.…”

Changes in brain 11C–nicotine binding sites in patients with mild Alzheimer’s disease following rivastigmine treatment as assessed by PET

“…These observations furthermore support findings of both preclinical (Grottick et al 2003) and clinical studies (Kadir et al 2006;Lawrence and Sahakian 1995), which suggest involvement of nicotinic receptors in attentional tasks. Interestingly, numerous clinical studies with different ChEIs suggest that anti-ChE therapy mainly ameliorate the attention domain of cognition (Alhainen et al 1993;Almkvist et al 2001;Sahakian et al 1993;Vellas et al 2005).…”

Beyond the Cholinergic Hypothesis: The Effect of Metrifonate and Other Cholinesterase Inhibitors on Neuropsychiatric Symptoms in Alzheimer’s Disease

“…Although deficits in episodic short-term memory are a prerequisite of AD, detailed analyses of neuropsychological domains responsive to tacrine suggest that selected attentional and executive functions are generally more responsive than learning and memory deficits per se [28,29]. Beyond its role in attention, memory and other intellectual functions, the central cholinergic system has a broad influence on cerebral functioning, including the modulation of sensory information processing, cortical arousal and motivational state [30,31].…”