Anti-Alzheimer's, Anti-Dementia Agents
Dementia is a chronic
disorder of the mental processes due to organic brain disease and organic
loss of intellectual functions. It is marked by memory disorders, changes
in personality, deterioration in personal care and impaired reasoning
ability. Alzheimer’s disease, also known as presenile dementia,
is a progressive form of dementia occurring in middle age, which is associated
with diffuse degeneration of the brain.
Vinpocetine (5 mg), Piracetam (400 mg)
Vinpocetine (5 mg), Piracetam (400 mg)
|| Research articles
on Anti-Alzheimer's and Anti-Dementia Agents
|Drug News Perspect. 2005 Jan;18(1):13-9.
Oxidative damage and Alzheimer's disease: Are antioxidant therapies useful?
Moreira PI, Smith MA, Zhu X, Honda K, Lee HG, Aliev G, Perry G.
Institute of Pathology, Case Western Research University, Cleveland, Ohio,
USA; Center for Neuroscience and Cell Biology of Coimbra, University of
Coimbra, Coimbra, Portugal. email@example.com.
Oxidative stress is
a key factor involved in the development and progression of Alzheimer's
disease, and it is well documented that free radical oxidative damage,
particularly of neuronal lipids, proteins, nucleic acids and sugars, is
extensive in brains of Alzheimer's disease patients. However, oxidative
stress may elicit compensatory responses and downstream adaptations such
as amyloid-beta deposition and neurofibrillary tangle formation, which
may function as "shields" to ensure that neuronal cells do not
succumb to oxidative injuries. Although during the past several years
our understanding of the mechanisms leading to neuronal damage and death
in the course of Alzheimer's disease has improved significantly, we have
not found an effective therapeutic to fight this devastating disorder.
However, the results obtained in clinical trials with antioxidants are
promising and propel us in the search of new and more effective antioxidant
|Neurology. 2005 Mar 8;64(5):899-901.
Hypertension and cognitive performance in African Americans with Alzheimer
Goldstein FC, Ashley AV, Freedman LJ, Penix L, Lah JJ, Hanfelt J, Levey
Department of Neurology, Emory University School of Medicine, 1841 Clifton
Road, N.E., Atlanta, GA 30329, USA. firstname.lastname@example.org
The authors examined the relationship between hypertension and cognitive
performance in 34 African-American patients with probable Alzheimer disease.
Multiple regression analyses indicated that hypertension was associated
with poorer overall performance on the Mattis Dementia Rating Scale, particularly
the Initiation/Perseveration and Conceptualization subscales, after controlling
for gender, age, and education. The findings suggest that African-American
patients with hypertension exhibit greater cognitive impairment, possibly
reflecting executive dysfunction.
|Ann N Y Acad Sci. 2004 Dec;1031:249-62.
Vitamin e in neurodegenerative disorders: Alzheimer's disease.
Kontush K, Schekatolina S.
INSERM Unite 551, Pavillon Benjamin Delessert, Hopital de la Pitie, 83 boulevard
de l'Hopital, 75651 Paris Cedex 13, France. email@example.com.
stress is important in the pathogenesis of Alzheimer's disease (AD). The
brain contains high levels of oxidizable lipids that must be protected
by antioxidants. Low concentrations of vitamin E, quantitatively the major
lipophilic antioxidant in the brain, are frequently observed in cerebrospinal
fluid (CSF) of AD patients, suggesting that supplementation with vitamin
E might delay the development of AD. In a placebo-controlled trial, vitamin
E (2000 IU/day, 2 years) slowed (-53%) functional deterioration in patients
with moderate AD (Sano et al., N. Engl. J. Med. 336: 1216-1222, 1997).
Recently, use of vitamin E and vitamin C supplements in combination was
found to be associated with reduced prevalence (-78%) and incidence (-64%)
of AD in elderly population (Zandi et al., Arch. Neurol. 61: 82-88, 2004).
These results are consistent with the ability of the supplementation with
vitamin E (400 IU/day, 1 month) to increase its levels in CSF (123%) and
plasma (145%) of AD patients and, in combination with vitamin C (1000
g/day), to decrease the susceptibility of CSF lipoproteins (up to -32%)
to in vitro oxidation (Kontush et al., Free Radic. Biol. Med. 31: 345-354,
2001). In addition, vitamin E reduced lipid peroxidation and amyloid deposition
in a transgenic mice model of AD (Sung et al., FASEB J. 18: 323-325, 2004).
Computer modeling of the influence of vitamin E on lipoprotein oxidation
reveals that the vitamin develops antioxidative activity in CSF lipoproteins
in the presence of physiologically relevant, low amounts of oxidants.
By contrast, under similar conditions, vitamin E behaves as a pro-oxidant
in plasma lipoproteins, consistent with the model of tocopherol-mediated
peroxidation (Stocker, Curr. Opin. Lipidol. 5: 422-433, 1994). This distinction
is related to major differences in the levels of vitamin E (50 nM vs.
30 muM) and oxidizable lipids (4 muM vs. 2.5 mM) between CSF and plasma,
which result in major differences in oxidative conditions (per unit of
vitamin E) between CSF and plasma in the presence of similar amounts of
oxidants. Altogether, these data suggest that vitamin E may be effective
against in vivo oxidation of CSF lipoproteins and brain lipids, and offer
new perspectives in the treatment of AD and other neurodegenerative disorders.
|Lijec Vjesn. 2004 Jul-Aug;126(7-8):211-4.
[Pharmacotherapy of Alzheimer's disease--an evidence based approach]
[Article in Croatian]
Boban M, Mahovic-Lakusic D, Babic T.
Klinika za neurologiju, KBC Zagreb.
The aim of this article is to provide
evidence-based recommendations for early diagnosis of Alzheimer's disease
(AD) and hereby to give clinican guidelines for optimal detection of patients
with AD. Our intention is also to unify diagnostic schemes in accordance
with our objective and specific possibilities. Basic diagnostic procedures
primarily are anamnesis and clinical examination with rational usage of
neuroimaging, electrophysiological and laboratory procedures. Using these
guidelines in medical practice in Croatia would be a good basis for future
epidemiological and clinical multicentric studies.
|Am Fam Physician. 2003 Oct 1;68(7):1365-72.
Pharmacologic treatment of Alzheimer's disease: an update.
Department of Family Medicine, Robert C. Byrd Health Sciences Center, West
Virginia University School of Medicine, Morgantown, West Virginia 26506,
Alzheimer's disease is characterized by the development of senile plaques
and neurofibrillary tangles, which are associated with neuronal destruction,
particularly in cholinergic neurons. Drugs that inhibit the degradation
of acetylcholine within synapses are the mainstay of therapy. Donepezil,
rivastigmine, and galantamine are safe but have potentially troublesome
cholinergic side effects, including nausea, anorexia, diarrhea, vomiting,
and weight loss. These adverse reactions are often self-limited and can
be minimized by slow drug titration. Acetylcholinesterase inhibitors appear
to be effective, but the magnitude of benefit may be greater in clinical
trials than in practice. The drugs clearly improve cognition, but evidence
is less robust for benefits in delaying nursing home placement and improving
functional ability and behaviors. Benefit for vitamin E or selegiline
has been suggested, but supporting evidence is not strong. Most guidelines
for monitoring drug therapy in patients with Alzheimer's disease recommend
periodic measurements of cognition and functional ability. The guidelines
generally advise discontinuing therapy with acetylcholinesterase inhibitors
when dementia becomes severe.
|Dement Geriatr Cogn Disord. 2003;16(1):15-24.
A large, community-based, open-label trial of donepezil in the treatment
of Alzheimer's disease.
Relkin NR, Reichman WE, Orazem J, McRae T.
Department of Neurology and Neuroscience, Weill Medical College of Cornell
University, New York, N.Y., USA.
This phase III trial was conducted to evaluate the safety and efficacy
of donepezil in Alzheimer's disease (AD) patients with a greater range
of comorbid conditions and concomitant medication use than those previously
evaluated in placebo-controlled studies. Patients (n = 1,035) with mild
to moderate probable or possible AD were enrolled from 255 sites in the
USA; 894 (86%) completed the trial. Mean age was 74.9 years (+/- 7.8);
baseline standardized Mini-Mental State Examination (sMMSE) score was
19.77 (+/- 5.4). Nearly all patients had at least 1 prior or comorbid
medical condition (97%) or were taking at least 1 concomitant medication
(93%). Safety assessments included recording treatment-emergent adverse
events (AEs). To confirm comparability with past studies, efficacy was
measured using the sMMSE. Over the 12-week study period, the mean sMMSE
score increased by 1.54 points over baseline (p < 0.0001) in donepezil-treated
patients. Most AEs (64%) were mild, and the occurrence of cholinergic-induced
AEs was significantly lower after a dose increase at 4 weeks than that
seen with a dose increase after 1 week in previous trials. Risk ratios
for gastrointestinal side effects were not significantly increased by
the use of aspirin or nonsteroidal anti-inflammatory drugs. Risk ratios
for bradycardia were not significantly increased by the use of beta-blockers,
nondihydropyridine calcium channel blockers or digoxin. Therefore, donepezil
improved cognition, as measured by the sMMSE, and was well tolerated despite
high concomitant medication use and extensive comorbidity. These results
highlight donepezil as a safe and effective treatment for AD patients
typically seen by community-based physicians.