Rationale for combining glutamatergic and cholinergic approaches in the symptomatic treatment of Alzheimer’s disease

2012 ◽  
Vol 12 (11) ◽  
pp. 1351-1365 ◽  
Author(s):  
Paul T Francis ◽  
Chris G Parsons ◽  
Roy W Jones
2006 ◽  
Vol 12 (5) ◽  
pp. 707-735 ◽  
Author(s):  
ELIZABETH W. TWAMLEY ◽  
SUSAN A. LEGENDRE ROPACKI ◽  
MARK W. BONDI

Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular. (JINS, 2006,12, 707–735.)


2019 ◽  
Vol 21 (25) ◽  
pp. 13578-13589 ◽  
Author(s):  
Shibaji Ghosh ◽  
Kalyanashis Jana ◽  
Bishwajit Ganguly

Donepezil, an acetylcholinesterase inhibitor, is an approved drug for the symptomatic treatment of Alzheimer's disease (AD).


2018 ◽  
Vol 33 (6) ◽  
pp. 385-393 ◽  
Author(s):  
Jakub Kazmierski ◽  
Chaido Messini-Zachou ◽  
Mara Gkioka ◽  
Magda Tsolaki

Cholinesterase inhibitors (ChEIs) are the mainstays of symptomatic treatment of Alzheimer’s disease (AD); however, their efficacy is limited, and their use was associated with deaths in some groups of patients. The aim of the current study was to assess the impact of the long-term use of ChEIs on mortality in patients with AD. This observational, longitudinal study included 1171 adult patients with a diagnosis of AD treated with donepezil or rivastigmine. Each patient was observed for 24 months or until death. The cognitive and functional assessments, the use of ChEIs, memantine, antipsychotics, antidepressants, and anxiolytics were recorded. The total number of deaths at the end of the observational period was 99 (8.45%). The patients who had received rivastigmine treatment were at an increased risk of death in the follow-up period. The higher risk of death in the rivastigmine group remained significant in multivariate Cox regression models.


1996 ◽  
Vol 6 ◽  
pp. 30
Author(s):  
R. Kumar ◽  
E. Cedar ◽  
M. Clark ◽  
J. Loudon ◽  
J. McCafferty ◽  
...  

Author(s):  
A.P. Porsteinsson ◽  
E.D. Clark

Alzheimer’s disease (AD) remains one of our greatest unmet medical needs, without any approved disease-modifying therapies. The emotional and financial burden of AD is enormous and predicted to grow exponentially with increasing median population age, posing a major public health problem. The potential to prevent or improve cognitive decline due to AD has important implications. There are medications currently approved for symptomatic treatment of AD, but they have limited clinical benefits and do not change the ultimate trajectory of the disease. The need to find effective treatments for AD that can prevent, slow, arrest, or even reverse the disease is ever more urgent and interventions that delay the symptomatic onset of AD would have a major public health impact (1).


2019 ◽  
Vol 25 (33) ◽  
pp. 3519-3535 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Mst. Marium Begum ◽  
Shanmugam Thangapandiyan ◽  
Md. Sohanur Rahman ◽  
...  

: In the brain, acetylcholine (ACh) is regarded as one of the major neurotransmitters. During the advancement of Alzheimer's disease (AD) cholinergic deficits occur and this can lead to extensive cognitive dysfunction and decline. Acetylcholinesterase (AChE) remains a highly feasible target for the symptomatic improvement of AD. Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AChE for myasthenia gravis had effectively proven that AChE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEIs) have been continued to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs which are under development and their respective mechanisms of actions.


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