A Pilot Study of Clonidine Plus Physostigmine in Alzheimer's Disease

Bierer, Linda M.; Aisen, Paul S.; Davidson, Michael; Ryan, Theresa; Schmeidler, James; Davis, Kenneth L.

doi:10.1159/000106731

Cited by 6 publications

(5 citation statements)

References 14 publications

(17 reference statements)

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“…In a final attempt to assess the efficacy of enhancing the adrenergic system to improve recent memory impairments in aged monkeys, we combined clonidine with the muscarinic cholinergic agonists arecoline or oxotremorine and again failed to find any improvement in performance (Bartus and Dean 1988a); in some cases, performance actually fell below baseline levels. Once again, good concordance was later seen between the results we obtained in our aged primate model and clinical trials in AD, for several tests of adrenergic agents have failed to provide any evidence of efficacy, including clonidine , another alpha-2-adrenergic agonist, guanfacine (Crook et al 1992;Schlegel et al 1989), as well as a pilot study with concurrent administration of clonidine and physostigmine in AD patients (Bierer et al 1994).…”

Section: A Look Forwardsupporting

confidence: 70%

Pharmaceutical treatment for cognitive deficits in Alzheimer’s disease and other neurodegenerative conditions: exploring new territory using traditional tools and established maps

Bartus¹,

Dean

2008

Psychopharmacology

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Despite the early promise shown by behavioral/functional approaches to develop treatment strategies, the dramatic shift in focus away from behavioral outcomes in animal neurodegenerative research that began 20 years ago has compromised further progress and continues to impede our ability to understand how these diseases impair human cognition and what pathways might lead to effective therapies. Principles applied successfully in the past should provide guidance for facilitating efforts in the future.

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Section: A Look Forwardsupporting

confidence: 70%

Pharmaceutical treatment for cognitive deficits in Alzheimer’s disease and other neurodegenerative conditions: exploring new territory using traditional tools and established maps

Bartus¹,

Dean

2008

Psychopharmacology

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“…ADAS is the main research instrument of AD in the last few years [33,34] and of possible thera peutic interventions [35][36][37][38], The scale is approved for use by the FDA [39], and by the respective agencies of the European Union [40] and Japan [41 ].…”

Section: Validation O F Adas In the Greek Populationmentioning

confidence: 99%

Alzheimer's Disease Assessment Scale: The Validation of the Scale in Greece in Elderly Demented Patients and Normal Subjects

Tsolaki

Fountoulakis²,

Nakopoulou³

et al. 1997

Dement Geriatr Cogn Disord

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Introduction: The Alzheimer Disease Assessment Scale (ADAS) is a scale specifically structured for the assessment of the cognitive decline and behavioral disorder seen in Alzheimer disease (AD) patients. Aim of the Study: The validation of ADAS in the Greek population. Material: One hundred and thirty-one subjects took part in the current study. Fifty of them were nondemented subjects (35 normal subjects and 15 suffering from age-associated memory impairment) and 81 demented patients (68 AD patients and 13 vascular dementia, VD, patients). Method: Diagnosis was made according to DSM-IV and NINCDS-ADRDA criteria. Hachinski Ischemia Scale was used to help to differentiate between AD and VD patients. Geriatric Depression Scale was used to quantify depressive symptomatology. MMSE and CAM-COG were used to assess the cognitive functioning of all subjects and FRSSD for the assessment of daily functioning. All subjects underwent a complete laboratory and biochemical testing, according to the protocol proposed in CAMDEX. All demented patients underwent brain CT. Results: ADAS-Cog discriminates perfectly AD patients and nondemented subjects at the score level of 13/14 and/or 14/15. Principal components analysis, using only AD patients, revealed 4 factors: cognitive, psychotic, depressive, and ''severe apraxia'' factors. Conclusion: ADAS is suitable for use in the discrimination between AD patients and nondemented subjects. It is also suitable for a more comprehensive assessment of the clinical symptomatology of AD patients, and for the evaluation of new therapeutic methods for AD, as well.

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“…In a double-blind, placebocontrolled study of persons with AD, clonidine produced no significant effects on cognitive function over several doses [40]. In a placebo-controlled study that combined the cholinesterase inhibitor, physostigmine, with clonidine in persons with AD, several people on this drug combination showed an improvement of 4 points or more on the Alzheimer's Disease Assessment Scale (ADAS) [41]. In a double-blind, 13-week trial of the alpha2 agonist guanfacine in persons with probable AD, the drug did not improve the course of the disease, and there was evidence of a negative effect of the drug on neuropsychological tests [42].…”

Section: Alpha2 Adrenergic Agonists and Antago-nistsmentioning

confidence: 99%

Is Elevated Norepinephrine an Etiological Factor in Some Cases of Alzheimers Disease?

Fitzgerald

2010

CAR

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Loss of norepinephrine (NE) releasing neurons, in the locus coeruleus of the brainstem, is well documented to occur in Alzheimer's disease (AD). However, this process does not necessarily result in decreased release of NE, since compensatory mechanisms may produce increased release of this neurotransmitter. Independent of potential loss of locus coeruleus cells, brain NE levels may be elevated in some persons with AD, both before and during disease progression. Here I examine evidence that elevated, endogenous brain NE is an etiological factor in some cases of AD, and not merely an epiphenomenon of the disease. To explore this etiological hypothesis in AD, I examine the following eight lines of evidence: 1) direct evidence of elevated NE or its metabolites in AD; 2) studies of tricyclic antidepressants, which may principally boost NE; 3) studies of clonidine and other alpha2 adrenergic agonist drugs, which may principally lower the concentration of NE; 4) studies of beta adrenoceptor blocking drugs, including propranolol; 5) comorbidity of AD and bipolar disorder, where both disorders may involve elevated NE; 6) comorbidity of AD and hypertension; 7) comorbidity of AD and obesity; and 8) potential interaction between AD and psychological stress, where stressors are known to release NE. These lines of evidence tend to support the elevated NE etiological hypothesis.

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A Pilot Study of Clonidine Plus Physostigmine in Alzheimer's Disease

Cited by 6 publications

References 14 publications

Pharmaceutical treatment for cognitive deficits in Alzheimer’s disease and other neurodegenerative conditions: exploring new territory using traditional tools and established maps

Pharmaceutical treatment for cognitive deficits in Alzheimer’s disease and other neurodegenerative conditions: exploring new territory using traditional tools and established maps

Alzheimer's Disease Assessment Scale: The Validation of the Scale in Greece in Elderly Demented Patients and Normal Subjects

Is Elevated Norepinephrine an Etiological Factor in Some Cases of Alzheimers Disease?

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