Effectiveness of treatment with donepezil hydrochloride and changes in regional cerebral blood flow in patients with Alzheimer's disease

Yoshida, Terufumi; Ha-Kawa, Sang Kil; Yoshimura, Masafumi; Nobuhara, Kenji; Kinoshita, Toshihiko; Sawada, Satoshi

doi:10.1007/s12149-007-0022-2

Cited by 37 publications

(63 citation statements)

References 24 publications

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“…A Cochrane review found that the three compounds display a small but short-lived cognitive benefit (Birks, 2006). In light of renewed interest in the AD circulation, cholinesterase inhibitors were revisited and found to preserve or improve perfusion in AD patients undergoing therapy (Nakano et al, 2001;Nobili et al, 2002;Rosengarten et al, 2006;Bär et al, 2007;Yoshida et al, 2007) (Figure 4). In the study by Bär et al (2007), 5-week galantamine administration improved CO 2 reactivity as measured in the middle cerebral artery of 17 AD patients with transcranial Doppler sonography.…”

Section: Cholinesterase Inhibitorsmentioning

confidence: 99%

“…This idea was further supported by the finding that patients whose cognitive score had stabilized or improved with cholinesterase inhibitor therapy, the so-called 'responders,' were also those who featured stabilized or increased perfusion, often within the first month of a 1-year treatment. Patients whose CBF had decreased during therapy were also those who had declined cognitively, the designated 'nonresponders' (Nakano et al, 2001;Nobili et al, 2002;Yoshida et al, 2007). The latter data highlighted the importance of targeting perfusion deficits as a means to influence mental status.…”

Section: Cholinesterase Inhibitorsmentioning

confidence: 99%

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Neurovascular function in Alzheimer's disease patients and experimental models

Nicolakakis

Hamel

2011

J Cereb Blood Flow Metab

133

118

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The ability of the brain to locally augment glucose delivery and blood flow during neuronal activation, termed neurometabolic and neurovascular coupling, respectively, is compromised in Alzheimer's disease (AD). Since perfusion deficits may hasten clinical deterioration and have been correlated with negative treatment outcome, strategies to improve the cerebral circulation should form an integral element of AD therapeutic efforts. These efforts have yielded several experimental models, some of which constitute AD models proper, others which specifically recapture the AD cerebrovascular pathology, characterized by anatomical alterations in brain vessel structure, as well as molecular changes within vascular smooth muscle cells and endothelial cells forming the bloodbrain barrier. The following paper will present the elements of AD neurovascular dysfunction and review the in vitro and in vivo model systems that have served to deepen our understanding of it. It will also critically evaluate selected groups of compounds, the FDA-approved cholinesterase inhibitors and thiazolidinediones, for their ability to correct neurovascular dysfunction in AD patients and models. These and several others are emerging as compounds with pleiotropic actions that may positively impact dysfunctional cerebrovascular, glial, and neuronal networks in AD.

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Section: Cholinesterase Inhibitorsmentioning

confidence: 99%

Section: Cholinesterase Inhibitorsmentioning

confidence: 99%

Neurovascular function in Alzheimer's disease patients and experimental models

Nicolakakis

Hamel

2011

J Cereb Blood Flow Metab

133

118

View full text Add to dashboard Cite

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“…The latter is portrayed functionally by a chronic cerebral hypoperfusion at rest and reduced perfusion to activated brain areas or impaired neurovascular coupling. Of interest, the decreases in cerebral blood flow (CBF) have been correlated with disease progression (Hirao et al, 2005) and with response to therapy (Yoshida et al, 2007). Recent evidence suggests that statins, cholesterol-lowering drugs broadly used in the treatment of cardiovascular diseases, have therapeutic potential in AD.…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Rescue by Simvastatin of Alzheimer's Disease Cerebrovascular and Memory Deficits

Tong¹,

Lecrux²,

Hamel³

2012

J. Neurosci.

147

162

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Alzheimer's disease (AD) is now established as a progressive compromise not only of the neurons but also of the cerebral vasculature. Increasing evidence also indicates that cerebrovascular dysfunction may be a key or an aggravating pathogenic factor in AD, emphasizing the importance to properly control this deficit when aiming for effective therapy. Here, we report that simvastatin (3-6 months, 40 mg/kg/d) completely rescued cerebrovascular reactivity, basal endothelial nitric oxide synthesis, and activity-induced neurometabolic and neurovascular coupling in adult (6 months) and aged (12 months) transgenic mice overexpressing the Swedish and Indiana mutations of the human amyloid precursor protein (AD mice). Remarkably, simvastatin fully restored short-and long-term memory in adult, but not in aged AD mice. These beneficial effects occurred without any decreasing effect of simvastatin on brain amyloid-␤ (A␤) levels or plaque load. However, in AD mice with recovered memory, protein levels of the learning-and memory-related immediate early genes c-Fos and Egr-1 were normalized or upregulated in hippocampal CA1 neurons, indicative of restored neuronal function. In contrast, the levels of phospholipase A2, enkephalin, PSD-95, synaptophysin, or glutamate NMDA receptor subunit type 2B were either unaltered in AD mice or unaffected by treatment. These findings disclose new sites of action for statins against A␤-induced neuronal and cerebrovascular deficits that could be predictive of therapeutic benefit in AD patients. They further indicate that simvastatin and, possibly, other brain penetrant statins bear high therapeutic promise in early AD and in patients with vascular diseases who are at risk of developing AD.

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“…This suggests that the effect of DNP on lifetime expectancy is not purely pharmacological. We previously reported [5] that the positive effects of SNH residency on AD were probably due to the following: First, DNP administration can improve psychomotor speed or attention [11,12], which is consistent with the higher mortality in older adults with lower perceptual speed [13]. Second, this improved cognitive function can smoothly lead to psychosocial intervention, and can increase the QOL.…”

Section: Positive Effect Of Dnp and Negative Effect Of Snh Residency mentioning

confidence: 57%

Lifetime Expectancy in Dementia with Lewy Bodies: Effects of Donepezil Administration and Special Nursing Home Replacement. A Retrospective Analysis in the Tajiri Project

Meguro¹,

Kumai²,

Takada³

et al. 2018

J Alzheimers Dis Parkinsonism

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life (QOL) of patients likely among AD patients [4]. Beyond delayed progression and increased QOL, the ultimate outcome of drug treatment should be measured in terms of lifetime expectancy.For such a long-term effect, we previously demonstrated a positive effect of DNP administration and a Special Nursing Home (SNH) replacement on lifetime expectancy after the onset of AD (without DLB) [5]. This may be due to the decreased mortality rate caused by reduction of concomitant diseases such as pneumonia. In the SNH, they can receive sophisticated psychosocial interventions. For AD patients, the similar lifetime expectancies in patients taking DNP at home and those not taking DNP in the SNH indicated a positive health economic effect of the drug; however, the effect for DLB is unclear. Herein, using the same database (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012) with additional database (2013)(2014)(2015)(2016)(2017), we re-analyzed the effects of DNP administration and/or SNH replacement on lifetime expectancy in DLB. IntroductionLifetime expectancy for patients with dementia, especially Alzheimer disease (AD) directly influences medical and care service needs and is a common question posed by families and patients. Brodaty et al.[1] compared mortality and survival in dementia with estimated lifetime expectancies in the general population. Survival after diagnosis of dementia varies considerably and depends on numerous factors and complex interactions among these factors. Relative loss of life expectancy decreases with age at diagnosis and also depends on gender, dementia subtype, and severity stage. A definitive meta-analysis of survival in dementia is precluded by deficiencies in primary studies.Following AD and vascular dementia (VaD), dementia with Lewy Bodies (DLB) has been reported to be the third main cause of dementia [2]. At present, there are no curative drugs for AD or DLB; however, symptomatic drugs, such as cholinesterase inhibitors (ChEIs), e.g. 1 donepezil (DNP), may delay progression (not biological but symptomatic) of the disease. We previously reported that the visual hallucinations manifested by DLB patients were also improved by DNP [3]. This effect combined with psychosocial interventions such as reality orientation and/or reminiscence approach may increase the quality of AbstractObjective: Cholinesterase inhibitors (ChEIs) can delay the progression of Alzheimer disease (AD). We previously demonstrated a positive effect of donepezil (DNP) administration and a Special Nursing Home (SNH) replacement on lifetime expectancy after the onset of AD. Recently DNP has been indicated for use in the treatment of dementia with Lewy Bodies (DLB); however, the effect on lifetime expectancy remains unclear. Herein, we analyzed the effects of DNP on DLB.Methods: All outpatients at the Tajiri Clinic with available medical records and death certificates from 1999-2012 were included in this retrospective analysis. The entry criteria were a diagnosis of dementia based on DSM-I...

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Effectiveness of treatment with donepezil hydrochloride and changes in regional cerebral blood flow in patients with Alzheimer's disease

Cited by 37 publications

References 24 publications

Neurovascular function in Alzheimer's disease patients and experimental models

Neurovascular function in Alzheimer's disease patients and experimental models

Age-Dependent Rescue by Simvastatin of Alzheimer's Disease Cerebrovascular and Memory Deficits

Lifetime Expectancy in Dementia with Lewy Bodies: Effects of Donepezil Administration and Special Nursing Home Replacement. A Retrospective Analysis in the Tajiri Project

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