Discrimination of tetrahydroaminoacridine responders by a single dose pharmaco-EEG in patients with Alzheimer's disease

Alhainen, Kari; Partanen, Juhani; Reinikainen, Kari; Laulumaa, Veikko; Airaksinen, Mauno M.; Riekkinen, Paavo

doi:10.1016/0304-3940(91)90907-b

Cited by 50 publications

(37 citation statements)

References 26 publications

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“…In fact, after a single oral dose of 50 mg, THA was shown to increase · activity and ·/ ratio only in patients without the Â-4 allele of the apolipoprotein E (ApoE) [49], whereas a better ·/ ratio was reported to predict who would have shown a good response to chronic therapy [50]. Moreover, increased mean qEEG frequencies in frontal areas have been reported after short-term THA administration [11], and better preserved frontal lobes have been suggested to characterize responders from non-responders [9,11,50]. Finally, higher EEG frequencies were shown to be better maintained in responders than in non-responders after 6 weeks of therapy [12], and global field power was reported to be reduced after 1 year of administration [13].…”

Section: Discussionmentioning

confidence: 99%

Quantitative EEG Changes in Alzheimer Patients during Long-Term Donepezil Therapy

Rodriguez¹,

Vitali²,

Leo³

et al. 2002

Neuropsychobiology

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Twenty patients affected with probable mild-to-moderate Alzheimer’s disease (AD; NINCDS-ADRDA criteria; 14 women and 6 men, mean age 75.2 ± 7.1 years) who regularly received an oral acetylcholinesterase inhibitor (AChEI; donepezil 5 mg/day; Dz group) were compared with a control group of 11 AD patients (6 women and 5 men, mean age 73.5 ± 6.0 years) diagnosed and followed up in the pre-AChEIs era (C group). At basal evaluation (t₀), the 2 groups were comparable for age, education, and severity of disease (Global Deterioration Scale). All patients underwent quantitative EEG (qEEG, average reference, 10–20 International System), and were reexamined about 1 year later (t₁; i.e., after 12.3 ± 3.6 months the Dz group, and after 13.7 ± 3.9 months the C group). Log-transformed values of two qEEG bands, i.e. 2–6 and 6.5–12 Hz, were averaged between adjacent channels (frontal F3 and F7, F4 and F8; parietotemporal P3 and T7, P4 and T8) to obtain a qEEG ratio (6.5–12/2–6 Hz.) from one frontal and one temporoparietal region in each hemisphere. Neuropsychological impairment was summarized by the Mini-Mental Status Examination (MMSE). At t₀, both the MMSE score and the qEEG ratio values were somewhat higher in the C than in the Dz group, although nonsignificantly. Between t₀ and t₁, the MMSE score decreased significantly (p < 0.01) more in the C group (–4.36 ± 2.25) than in the Dz group (–1.45 ± 2.16), as did the qEEG ratio in the right frontal region (p < 0.01), whereas in the left frontal region the significance level was not reached (p = 0.02). Between t₀ and t₁, the qEEG ratio difference in both frontal regions and in the right temporoparietal region significantly correlated with the MMSE difference (p < 0.01), but neither with time between examinations nor with the difference on the Visual Search Test score. Long-term treatment with Dz led to a lesser deterioration of qEEG, paralleling a milder neuropsychological decline. The effect was significant in frontal regions, possibly because they are relatively spared during the mild-to-moderate phases of the disease.

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Section: Discussionmentioning

confidence: 99%

Quantitative EEG Changes in Alzheimer Patients during Long-Term Donepezil Therapy

Rodriguez¹,

Vitali²,

Leo³

et al. 2002

Neuropsychobiology

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“…In the current study, we investigate the single-dose response. In an open trial, responders to a single dose of 50 mg of tacrine showed favorable effects on the alpha/theta ratio in EEG and neuropsychological tests tapping the attentional function [8,28]. To our knowledge, there is only one previous study on the single-dose response with tacrine and no study for the other cholinesterase inhibitors.…”

Section: Introductionmentioning

confidence: 98%

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

Almkvist¹,

Jelić²,

Amberla³

et al. 2000

Dement Geriatr Cogn Disord

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A proportion of Alzheimer’s disease (AD) patients treated for several months with cholinesterase (ChE) inhibitors have shown some favorable response on cognition, but the characteristics of the responders are still unclear. This study attempts to identify the characteristics of individuals with a positive behavioral response after a double-blind randomized administration of a single oral dose of tacrine (40 mg) and placebo to AD patients. Furthermore, the relationship between single-dose and long-term responders are examined. Twenty-four mildly to very mildly demented AD patients participated in the study. They all fulfilled the diagnosis of probable AD according to NINCDS-ADRDA criteria. Active treatment (tacrine 40 mg) and placebo was administered in random order on 2 consecutive days, and the effects were evaluated within 2 h using neuropsychological tests (assessing visuospatial ability, episodic memory and attention), registration of EEG activity and measurement of red blood cells (RBC) acetylcholinesterase (AChE), ChE activity and concentrations of tacrine and its metabolites in plasma. Results demonstrated significant improvement, tacrine compared to placebo, in measures of attention, but not in episodic memory or visuospatial ability. A single-dose response was therefore defined in terms of improvement in attention. The tacrine plasma concentration (pcTHA) showed a positively skewed distribution (mean ± SD: 10.5 ± 11.8, range: 1.0–51.8 ng/ml). There were no significant differences between single-dose responders compared to nonresponders in pcTHA, metabolites of tacrine, inhibition of AChE in RBC, tau levels in CSF, AChE activity in CSF or plasma and demographic variables. However, single-dose responders showed a higher right frontal alpha/theta ratio on EEG and had lower glucose metabolism in the parietal-temporal association cortex at baseline. In addition, the frequency of apolipoprotein E (APOE) Ε4 alleles was higher in responders. Interestingly, the single-dose response was related to the long-term response, although not significantly, which probably was due to lack of power. To conclude, the present study identified single-dose responders in terms of improved attentional performance associated with a relatively higher alpha/theta activity in the right frontal regions of the brain measured on EEG and predominance of APOE Ε4 allele.

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“…physostigmine) have tended to exert an opposing action, reducing slow-wave power, augmenting fastwave power and generally shifting the EEG power spectrum of patients into more normal patterns [41]. Confirmation of the activational profile of nicotine in DAT on EEG is of particular interest in that it resembles, in part, the acute test dose profile observed with efficacious stimulants and nootropic agents [42], a profile which is more evident with favorable patient response to a range of antidementing agents [43][44][45][46], including the cholinesterase inhibitor THA [47][48][49].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2000

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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.

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Discrimination of tetrahydroaminoacridine responders by a single dose pharmaco-EEG in patients with Alzheimer's disease

Cited by 50 publications

References 26 publications

Quantitative EEG Changes in Alzheimer Patients during Long-Term Donepezil Therapy

Quantitative EEG Changes in Alzheimer Patients during Long-Term Donepezil Therapy

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

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

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