A pharmacogenomic approach to Alzheimer's disease. 

Cacabelos R, Alvarez A, Fenandez-Novoa L, Lombardi VR.

EuroEspes Biomedical Research Center,
 Institute for CNS Disorders, La Coruna, Spain.
Acta Neurol Scand Suppl 2000;176:12-9 

Abstract

Single nucleotide polymorphisms (susceptibility genetics) and genomic point mutations (mendelian genetics) can be used in Alzheimer's disease (AD) for diagnostic, predictive and therapeutic purposes. Using a matrix genetic model, including APOE, PS1 and PS2 allelic variants, we have studied the distribution of 36 different genotypes in the AD population (N= 479) and the genotype-related cognitive response to a multi-factorial therapy in AD patients with mild-to-moderate dementia. The 10 most frequent AD genotypes are the following: 1) E33P112P2 + (17.75%), 2) E33P112P2- (15.55%), 3) E33P111P2+ (10.85%), 4) E34P112P2+ (9.60%), 5) E34P112P2- (7.56%), 6) E33P111P2- (7.10%), 7) E34P111P2+ (4.80%), 8) E33P122P2+ (4.38%), 9) E34P111P2- (4.18%), and 10) E34P122P2+ (3.55%). APOE-4/4-related genotypes represent less than 3% in the following order: E44P112P2 + > E44P111P2+ = E44P111P2- > E44P112P2+ > E44P122P2+ = E44P122P2.  Multi-factorial therapy with CDP-choline (1,000 mg /day) + piracetam (2,400 mg/day) + anapsos (360 mg/day) did improve mental performance during the first 6-15 months in a genotype-specific fashion. The best responders in the APOE series were patients with APOE-3/4 genotype (r= +0.013), while the worst responders were APOE-4/4 patients (r= -0.93). PS1-related genotypes responded in a similar manner; and patients with a defective PS2 gene exon 5 (PS2+) always showed a poorer therapeutic response than PS2- patients. All these data suggest that the therapeutic outcome in AD exhibits a genotype-specific pattern, and that a pharmacogenomic approach to AD might be a valuable strategy for drug development and monitoring.

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Deprenyl Alzheimer's research                                                   www.deprenyl.info
       deprenyl   improves the performance of patients with Alzheimer's disease
       deprenyl   in the treatment of Alzheimer's disease
CDP Choline Alzheimer's research        !                                 www.cdpcholine.info
       CDP choline  may be useful in the treatment of Alzheimer's
       CDP choline  significant improvement after 1 month in early-onset Alzheimer's
       CDP choline  effects on cognition in patients with Alzheimer's
       CDP choline  significant improvement in Alzheimer's after 1 month  
       CDP choline  improved mental performance in Alzheimer's
Vinpocetine Alzheimer's research                  !                         www.vinpocetine.info
       vinpocetine  enhances oxygen release in vascular dementia  . 
       vinpocetine  article 
Piracetam Alzheimer's research                   !                            www.piracetam.info
       piracetam  improved alertness in Alzheimer's patients
       piracetam  improved cerebral glucose metabolism in Alzheimer's patients
       piracetam  use in Alzheimer's
       piracetam  therapy in Alzheimer's
       piracetam  a one year study of Alzheimer's patients 
       piracetam  article
Idebenone Alzheimer's research                      !                       www.idebenone.info
       Idebenone  versus Tacrine in Patients with Alzheimer's disease
       Idebenone  efficacy of idebenone in the treatment of Alzheimer's disease
       Idebenone  Nerve Growth Factor synthesis stimulators in Alzheimer's disease
       Idebenone  in the treatment of dementia of the Alzheimer type
       Idebenone  cognitive enhancement therapy for Alzheimer's disease
       Idebenone  study in the treatment of Alzheimer's disease
       Idebenone  two year study indicates idebenone slows Alzheimer's progression
       Idebenone  stimulates NGF synthesis in the treatment of Alzheimer's disease
       Idebenone  article
Pyritinol Alzheimer's research                          !                        www.pyritinol.info
       pyritinol  improved cognition in 100 dementia patients
       pyritinol  produced significant improvement in 40 dementia patients
       pyritinol  had therapeutic effect on 156 senile dementia patients
       pyritinol  improved cognitive performance in 26 dementia patients
       pyritinol  improved cerebral glucose metabolism in dementia
       pyritinol  article
 
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Memantine Alzheimer's research                                              www.memantine.info

       Memantine  efficacy in patients with dementia
       Memantine  in senile dementia, Alzheimer type
       Memantine  and advanced dementia
       Memantine  for neuroprotection in dementia
       Memantine  in vascular dementia
       Memantine  in mild to moderate dementia
Galantamine Alzheimer's research                                            www.galantamine.cc
       galantamine  efficacy of galantamine in dementia and Alzheimer's disease
       galantamine  for Alzheimer's disease
       galantamine  novel approach to the treatment of Alzheimer disease
       galantamine  maintaining cognitive function in Alzheimer disease
       galantamine  maintaining functional abilities in Alzheimer disease
       galantamine  a new Alzheimer disease drug with a past life
       galantamine  treating vascular dementia with galantamine
       galantamine  rationale for switching from donepezil to galantamine
       galantamine  switching previous therapies for Alzheimer's disease to galantamine
       galantamine  its use in Alzheimer's
       galantamine  a new treatment for Alzheimer's
       galantamine  benefits to Alzheimer's patients
       galantamine  efficacy in mild to moderate Alzheimer's disease
       galantamine  effects on the course of Alzheimer's disease
       galantamine  a 5 month Alzheimer's study
       galantamine  effects in patients previously treated with donepezil
       galantamine  a six month Alzheimer's study
       galantamine  therapeutic effects beyond cognition in Alzheimer's disease
       galantamine  cognitive function in Alzheimer's disease
       galantamine  maintains cognitive function for at least 1 year
       galantamine  increase the density of brain nicotinic receptors
       galantamine  treatment for mild to moderate Alzheimer's disease.
       galantamine  may be effective as a cognition-enhancer in Alzheimer's disease
       galantamine  differs from other acetylcholine esterase inhibitors
       galantamine  safety and tolerability
       galantamine  dual mode of action for Alzheimer's disease
       galantamine  provides benefits for Alzheimer's for up to six months  .  
            article    Galantamine fights Alzheimer's
            article    Why galantamine is better than Aricept® and Exelon ®
            article    Galantamine can sharpen your mental edge
            article    Galantamine helps save memory
            article    Galantamine for combating mental decline
            article    Galantamine opens the channels of your memory
            article    Galantamine boosts memory
            article    Galantamine rescues brain cells
            article    Galantamine helps your memory
            article    Galantamine memory enhancement therapy
            article    Galantamine may help stave off dementia
            article    Galantamine enhances neurotransmission
            article    Galantamine increases acetylcholline
            article    Galantamine has benefits over Aricept®

Alzheimer's disease
    piracetam  and Alzheimer's 
    piracetam  therapy in Alzheimer's
    piracetam  use in Alzheimer's
    piracetam  induced changes in Alzheimer's
    piracetam  effect on Alzheimer's
    piracetam  reverses hippocampal changes in Alzheimer's
    piracetam  and Alzheimer's disease
    piracetam  controlled study on dementia
    piracetam  effect on senile dementia memory
Alcoholism
    piracetam  in acute alcohol withdrawal
    piracetam  alcoholic treatment
    piracetam  efficacy in chronic alcoholics
    piracetam  effect on alcoholics
Child birth
    piracetam  in parturients and newborn infants
    piracetam  reduced duration of labor
    piracetam  protective effect during delivery
    piracetam  concentrations during delivery
Circulatory Disorders
    piracetam  effectiveness in cerebral arteriosclerosis
    piracetam  and chronic cerebrovascular disorders
    piracetam  effect on brain circulation failure
Dyslexia
    piracetam  learning aid in dyslexia
    piracetam  in children with dyslexia
    piracetam  in students with dyslexia
    piracetam  efficacy in dyslexic reading and writing disorders
    piracetam  verbal effect in dyslexic boys
    piracetam  improves reading in dyslexia
Head injury
    piracetam  and concussion
    piracetam  effect on consciousness due to head injury
    piracetam  protection in brain injury
    piracetam  use in severe brain injury
Hearing loss
    piracetam  use in sudden deafness
    piracetam  sudden hearing loss treatment
    piracetam  in tinnitus and sudden deafness
    piracetam  treatment of sudden deafness
Heart Disease
    piracetam  effects on arterial hypertension
    piracetam  effect on elderly coronary heart disease
    piracetam  in chronic ischemic heart disease
    piracetam  in ischemic heart disease
    piracetam  in myocardial infarct patients
Mental Performance
    piracetam  improved mental performance
    piracetam  and nootropics
    piracetam  in patients with mental decline 
    piracetam  effects on cognitive functions
    piracetam  improves memory
    piracetam  efficacy in cognitive impairment
    piracetam  memory impairment trial
    piracetam  and EEG of boys with learning disorders
    piracetam  effect on adolescent brain function
    piracetam  effects on human EEG
    piracetam  on change in brain functional state
    piracetam  effects on brain functions
    piracetam  in elderly cerebral impairment
    piracetam  in cerebral impairment
Stroke
    piracetam  in secondary stroke prophylaxis
    piracetam  improves blood flow of post-stroke patients
    piracetam  improves aphasia in acute stroke
    piracetam  in the treatment of acute stroke
    piracetam  evaluation in acute stroke
    piracetam  in stroke-unduced Aphasia
    piracetam  treatment in ischemic stroke
    piracetam  treatment of patients with an ischemic stroke
    piracetam  acute stroke study
    piracetam  effect on post-stroke recovery
    piracetam  improvement in Stroke
    piracetam  adjuvant to language therapy for aphasia
Vertigo
    piracetam  treatment for vertigo
    piracetam  is effective in vertigo
    piracetam  effect in 55 vertigo patients
    piracetam  subjective improvement in vertigo
    piracetam  significantly reduced vertigo symptoms
Myoclonus
    piracetam  and reduction of myoclonus
    piracetam  relieves symptoms in myoclonus epilepsy
    piracetam  in cortical myoclonus
    piracetam  and progressive myoclonus epilepsy
    piracetam  in patients with myoclonus
    piracetam  in progressive myoclonus epilepsy
    piracetam  promising results in myoclonus epilepsy
    piracetam  long-term efficacy in myoclonus epilepsy
    piracetam  beneficial use for severe myoclonus epilepsy
    piracetam  beneficial effect on post-ischaemic myoclonus
Raynaud's
    piracetam  treatment of Raynaud's
    piracetam  evidence for its anti-platelet effect in Raynaud's
    piracetam  platelet anti-aggregant properties
Sickle Cell disease
    piracetam  treatment of children with sickle cell disease
    piracetam  improves sickle cell deformability
    piracetam  crises management of sickle cell disease
Misc.
    piracetam  mechanism of action
    piracetam  elevates cholinergic receptor density
    piracetam  cholinergic receptor function in mice
    piracetam  effects on schizophrenia
    piracetam  effect on cerebral glucose utilization
    piracetam  improved driving in elderly motorists
    piracetam  unique mode of action
    piracetam  study age-related memory disorders
    piracetam  psychological treatment
    piracetam  and aging
    piracetam  and vigilance
    piracetam  versus acetylcholinesterase inhibitors
    piracetam  effects on arterial hypertension
    piracetam  in cerebral palsy
    piracetam  auxiliary treatment of cerebral palsy
    piracetam  interaction in the motor cortex
    piracetam  effect on consciousness after neurosurgery
    piracetam  effect on cerebral infarction
    piracetam  improves cognitive deficits in early Parkinsonism
    piracetam  therapy in recurrent duodenal ulcer
    piracetam  efficacy in recurrence of duodenal ulcer
    piracetam  efficacy in breath-holding spells
    piracetam  treatment of migraine
    piracetam  treatment of soft tissue rheumatism 
    piracetam  effect on intellectually deficient children
    piracetam  effect on neuroleptic-induced side effects
    piracetam  improved school-performance in legasthenia

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