Cerebral Pharmacodynamics of Physostigmine in Alzheimer's Disease Investigated Using Single-Photon Computerised Tomography

We attempted to identify the characteristic patterns in regional cerebral blood flow (rCBF) of patients with Alzheimer’s disease who responded to donepezil therapy. Sixty-one patients treated with donepezil were divided into two groups (responders and nonresponders) on the basis of changes in their Mini Mental State Examination (MMSE) scores from baseline to study endpoint. We analyzed single-photon emission computed tomography data (SPECT) at baseline using three-dimensional stereotactic surface projections and compared differences in rCBF between the two groups. Statistical maps showed a significantly lower rCBF of the lateral and medial frontal lobes in the nonresponders than in the responders. There was a significant inverse correlation between the relative rCBF reduction in the frontal lobe and the MMSE change. These results suggest that frontal function, as assessed by SPECT, affects the patient’s response to treatment with donepezil. Measuring rCBF may aid in the selection of possible treatment responders.

Section: Discussionmentioning

confidence: 99%

Regional Cerebral Blood Flow Patterns and Response to Donepezil Treatment in Patients with Alzheimer’s Disease

Hanyu¹,

Shimizu²,

Tanaka³

et al. 2003

“…Donepezil also improved psychomotor speed and attention as well as memory in patients with Parkinson's disease [41]. Furthermore, AD patients with lower perfusion in the orbitofrontal cortex may respond behaviorally to ChEI [8], and a short-acting ChEI, physostigmine, may in turn increase frontal perfusion [42]. Taken together, executive dysfunction caused by HBP, PVH, AD per se or even Parkinson's disease may be likely to respond to donepezil through improvement of the frontal-subcortical cholinergic interaction [7].…”

Section: Discussionmentioning

confidence: 99%

Do Vascular Lesions and Related Risk Factors Influence Responsiveness to Donepezil Chloride in Patients with Alzheimer’s Disease?

Fukui

Taguchi²

2005

The purpose was to identify vascular influences on the responsiveness to donepezil chloride. The study included 50 untreated probable Alzheimer’s disease patients with the Modified Hachinski Ischemic Score <4. We assessed baseline cognitive status using the Revised Hasegawa Dementia Scale (HDS-R), Clinical Dementia Rating (CDR) and the clock drawing test (CDT). The response to 5 mg of donepezil was monitored by the CDT for 12 months. Patients were classified as true responders (TR), unchanged (UC) and non-responders according to changes on the CDT in response to treatment. High HDS-R scores, low CDT scores, low CDR and presence of hypertension (HBP) and periventricular hyperintensities (PVH) predicted a TR- or UC-type outcome. Aggravation of executive function by HBP and/or PVH and its improvement by donepezil may have been detected by the CDT.

“…Up to now only few activation studies have been per formed in (S)DAT [36][37][38][39][40][41][42][43][44][45]. Those using physostigmine infusion as stimulus [36][37][38][39][40] described an increased CBF following drug administration in patients.…”

mentioning

confidence: 99%

“…Those using physostigmine infusion as stimulus [36][37][38][39][40] described an increased CBF following drug administration in patients. However, only one of these studies had a control group and revealed an increase of CBF only in the patient group [39], but there was a 1-week time interval between the investigations.…”

mentioning

confidence: 99%

Cerebrovascular Reactivity to Acetazolamide in (Senile) Dementia of Alzheimer’s Type: Relationship to Disease Severity

Stoppe¹,

Schütze²,

Kögler

et al. 1995

Neuropathological reports about denervation and amyloid angiopathy in dementia of Alzheimer''s type (DAT) as well as signs of selective incomplete white matter infarctions point to a vascular involvement within the degenerative process. In order to investigate potential alterations of cerebrovascular function we performed cerebral blood flow measurements before and after intravenous injection of 1 g acetazolamide using technetium-99m hexamethylpropyleneamine oxime and single photon emission tomography in 12 patients (6 female, 6 male; mean age 70.8 ± 9.6 years) with probable (senile) dementia of Alzheimer''s type (SDAT) and 9 controls (7 female, 2 male; mean age 71.2 ± 8.6 years). SDAT patients revealed significantly reduced cerebrovascular reactivity with lower values with increasing cognitive impairment. We discuss possible underlying mechanisms.