Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls: a dose-response study

Sunderland, Trey; Pn, Tariot; Rm, Cohen; Weingartner, Herbert; Ea, Mueller; Murphy, Douglas B.

doi:10.1097/00002093-198701040-00036

Cited by 52 publications

(70 citation statements)

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“…The hypersensitivity to scopolamine, which has been demonstrated in elderly participants when compared to younger participants (Flicker et al, 1992;Ray et al, 1992;Zemishlany and Thorne, 1991) and in participants with AD when compared to non-demented elderly participants (Sunderland et al, 1987), is consistent with the well-established age-and AD-related changes in a number of markers, including reductions in the size and number of cholinergic neurons in the NBM (McGeer et al, 1984;Whitehouse et al, 1982). Thus, the increased cognitive toxicity to trihexyphenidyl that we observed in participants with the APOE-e4 allele may reflect some form of decreased cholinergic function or reserve in this population.…”

Section: Discussionmentioning

confidence: 99%

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

Pomara

Willoughby

Wesnes³

et al. 2003

Neuropsychopharmacol

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The degree to which elderly adults experience cognitive impairments from centrally acting anticholinergic drugs is variable, but the cause of this variability is unknown. The present study examined the e4 allele as a possible modulator of the effects of trihexyphenidyl hydrochloride (Artane t ), an anticholinergic drug, on memory functioning. Of the 24 cognitively intact, elderly participants (age range 62-76), 12 who possessed the e4 allele, participated in a double-blind, randomized, placebo-controlled, crossover, three-way study. All participants were tested after receiving a single oral dose of trihexyphenidyl (1 or 2 mg) or placebo, with a 7-day washout period between sessions. Memory and psychomotor tests were administered at baseline, and at 1, 2.5, and 5 h post-treatment. Results showed that participants with the e4 allele demonstrated significant impairments in delayed recall after both 1 and 2 mg doses of trihexyphenidyl while the non-e4 group did not. Additionally, while acute administration of the 2 mg dose significantly impaired total recall in both e4 and non-e4 carriers, the e4 carriers showed a more persistent impairment. These findings held when participants with the e2 allele were excluded from the analyses. The e4 groups did not differ with respect to psychomotor performance or plasma drug levels. These results provide evidence suggesting that the e4 allele plays a significant role in increasing cognitive sensitivity to trihexyphenidyl and that a temporal component of memory consolidation may be especially vulnerable. A larger study is warranted to confirm these preliminary findings.

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Section: Discussionmentioning

confidence: 99%

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

Pomara

Willoughby

Wesnes³

et al. 2003

Neuropsychopharmacol

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“…Scopolamine was administered intravenously because oral scopolamine has variable absorption, poor bioavailability, and is behaviorally less effective (Nuotto, 1983;Putcha et al, 1989). The dose of scopolamine was chosen because intravenous injections in this dose range have been reported to affect a variety of cognitive f unctions (Sunderland et al, 1987;Martinez et al, 1997;Vitiello et al, 1997). Scopolamine was administered 80 min before scanning, because previous studies have shown that cognitive effects of intravenous scopolamine peak from 90 to 150 min after administration (Safer and Allen, 1971;Sannita et al, 1987;Curran et al, 1991b;Ebert et al, 1998).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Modulation of Behavioral and Neuronal Correlates of Repetition Priming

Thiel¹,

Henson

Morris³

et al. 2001

J. Neurosci.

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In this experiment we address the pharmacological modulation of repetition priming, a basic form of learning, using eventrelated functional magnetic resonance imaging. We measured brain activity in a word-stem completion paradigm in which, before study, volunteers were given either placebo, lorazepam (2 mg orally), or scopolamine (0.4 mg, i.v.). Relative to placebo, both drugs attenuated the behavioral expression of priming. Repetition was associated with a decreased neuronal response in left extrastriate, left middle frontal, and left inferior frontal cortices in the placebo group. Both drugs abolished these "repetition suppression" effects. By showing a concurrence of behavioral and neuronal modulations, the results suggest that GABAergic and cholinergic systems influence the neuronal plasticity necessary for repetition priming.

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“…Scopolamine was administered IV because oral scopolamine has variable absorption, poor bioavailability, and is behaviorally less effective (Putcha et al 1989;Nuotto 1983). The dose of scopolamine was chosen because IV injections in this dose range have been reported to affect a variety of cog-nitive functions (Sunderland et al 1987;Martinez et al 1997;Vitiello et al 1997). Scopolamine was administered 80 min before scanning, as prior studies have shown that cognitive effects of parenteral scopolamine peaks from 90 to 150 min after administration (Safer and Allen 1971;Sannita et al 1987;Ebert et al 1998).…”

Section: Drugsmentioning

confidence: 99%

Scopolamine but Not Lorazepam Modulates Face Repetition Priming A Psychopharmacological fMRI Study

Thiel

Henson

Dolan

2002

Neuropsychopharmacology

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Repetition priming is a basic form of learning associated with decreased neuronal responses following stimulus repetition. In this experiment, we address cholinergic and GABAergic modulation of repetition priming in a face recognition paradigm. In experiment 1, we used eventrelated functional magnetic resonance imaging (fMRI) inRepetition priming is a basic form of learning defined behaviorally as facilitated or biased processing of previously encountered stimuli. One possible neuronal signature of this form of learning is "response suppression," a decrement in the neuronal response to repeated stimulation that has been shown in monkeys (Desimone 1996). Measures of repetition priming in humans include pattern completion, object identification, or word-stem completion tasks (Schacter 1994). When using such tasks in conjunction with neuroimaging methods, studies have consistently found decreased hemodynamic responses in posterior cortical regions when items are repeated (Squire et al. 1992;Buckner et al. 1998;Buckner et al. 2000;Badgaiyan 2000;van Turennout et al. 2000 successfully demonstrated a human analog to the decreased neural firing observed in monkey cortex, which is referred to as "repetition suppression." Using a word-stem completion task, we have previously shown that "repetition suppression" is modulated by GABAergic and cholinergic neurotransmitter systems (Thiel et al. 2001). Both lorazepam and scopolamine decreased the size of repetition suppression effect in posterior and frontal cortical regions. Both drugs also impaired the behavioral index of repetition priming, suggesting that GABAergic and cholinergic systems modulate neuronal plasticity necessary for priming in this paradigm. The behavioral impairments with lorazepam were consistent with prior studies using picture-fragment completion, word-fragment completion, or wordstem completion tasks Vidailhet et al. 1994;Vidailhet et al. 1999;Danion et al. 1992;Brown et al. 1989). Behavioral impairments of repetition priming with scopolamine, on the other hand, were not in line with the majority of prior studies (Knopman 1991;Danion et al. 1990;Schifano and Curran 1994), and we suggested that these differences could be caused by a lower active dose used in these previous studies (see Thiel et al. 2001 for discussion).The rationale for the present study was to further investigate GABAergic and cholinergic modulation of repetition priming, using a paradigm involving face recognition (Ellis et al. 1990). This paradigm investigates priming of faces and its modulation by familiarity (i.e., famous vs. unfamous faces). Whereas the paradigm has been used in several psychological and neuroimaging studies (Ellis et al. 1990;Brunas-Wagstaff et al. 1992;Henson et al. 2000;Henson et al. 2002), its pharmacological modulation has not previously been investigated. Functional magnetic resonance imaging (fMRI) studies using repeated, intermixed presentations of famous and unfamous faces in implicit face priming paradigms have shown greater responses to famous than unfam...

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Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls: a dose-response study

Cited by 52 publications

References 0 publications

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

Pharmacological Modulation of Behavioral and Neuronal Correlates of Repetition Priming

Scopolamine but Not Lorazepam Modulates Face Repetition Priming A Psychopharmacological fMRI Study

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