Alzheimer Disease: Hake AM

Hake AM. · Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA. · Semin Neurol. · Pubmed #12170395 No free full text.

Abstract: Alzheimer's disease (AD) is the most common form of dementia, and its incidence increases with age. Treatment with cholinesterase inhibitor drugs is currently the standard of care. Several other medications and nonpharmacologic therapies are also available for the treatment of cognitive decline and other symptoms of AD. This article reviews the current recommendations for the treatment of Alzheimer's disease.

Hake AM, Farlow MR. · Indiana University School of Medicine, Department of Neurology, Indianapolis, IN 46202, USA. · Expert Opin Pharmacother. · Pubmed #11825329 No free full text.

Abstract: There are currently four compounds approved for use in the treatment of Alzheimer's disease (AD). These drugs are all cholinesterase (ChE) inhibitors, which are thought to provide predominantly symptomatic benefits by increasing the level of acetylcholine (ACh) in the synapse. Although there are slight differences in the mechanisms of action of these compounds, it remains to be determined whether any one of them has a significant therapeutic advantage over the others. Several other drugs have also been investigated for their potential use as either symptomatic or disease-modifying agents in the treatment of AD, with mixed results. Current therapeutic research is focused on addressing the underlying pathology of AD, in the hope of arresting or reversing the course of the disease. This review will provide an overview of the ChE inhibitors and other drugs used for treating the symptoms of AD, summarise the results of recent therapeutic trials, discuss directions of future research and outline the current treatment recommendations for AD.

Hake AM. · Department of Neurology, Indiana University School of Medicine, Indianapolis 46202, USA. · Cleve Clin J Med. · Pubmed #11453078 links to  free full text

Abstract: The four cholinesterase inhibitors now available for treatment of Alzheimer disease (AD) may be most beneficial, especially in the long run, if started early in the course of the disease. This paper reviews the efficacy, pharmacokinetics, metabolism, side effects, dosage, and precautions for the use of these agents, which may produce modest improvements in cognition, behavior, and the ability to perform activities of daily living.

Henderson VW, Paganini-Hill A, Miller BL, Elble RJ, Reyes PF, Shoupe D, McCleary CA, Klein RA, Hake AM, Farlow MR. · Department of Neurology, University of Southern California, Los Angeles 90089, USA. · Neurology. · Pubmed #10668686 No free full text.

Abstract: BACKGROUND: AD, the most prevalent cause of dementia, affects twice as many women as men. Therapeutic options are limited, but results of prior studies support the hypothesis that estrogen treatment may improve symptoms of women with this disorder. METHODS: Forty-two women with mild-to-moderate dementia due to AD were enrolled into a randomized, double-blind, placebo-controlled, parallel-group trial of unopposed conjugated equine estrogens (1.25 mg/day) for 16 weeks. RESULTS: Outcome data were available for 40 women at 4 weeks and 36 women at 16 weeks. At both 4 and 16 weeks, there were no significant differences or statistical trends between treatment groups on the primary outcome measure (the cognitive subscale of the Alzheimer's Disease Assessment Scale), clinician-rated global impression of change, or caregiver-rated functional status. Exploratory analyses of mood and specific aspects of cognitive performance also failed to demonstrate substantial group differences. CONCLUSION: Although conclusions are limited by small sample size and the possibility of a type II error, results suggest that short-term estrogen therapy does not improve symptoms of most women with AD. These findings do not address possible long-term effects of estrogen in AD, possible interactions between estrogen and other treatment modalities, or putative effects of estrogen in preventing or delaying onset of this disorder.

Hake AM, Farlow MR. · Department of Neurology, Indiana University School of Medicine, 541 Clinical Drive, Suite 299, Indianapolis, IN 46202, USA. · Clin Geriatr Med. · Pubmed #15062492 No free full text.

This publication has no abstract.

Murrell JR, Hake AM, Quaid KA, Farlow MR, Ghetti B. · Department of Pathology and Laboratory Medicine, 635 Barnhill Dr, Medical Science Bldg A128, Indianapolis, IN 46202, USA. · Arch Neurol. · Pubmed #10867787 links to  free full text

Abstract: CONTEXT: Alzheimer disease is the most common form of dementia. Mutations in the genes amyloid precursor protein (APP), presenilin 1(PS1) and presenilin 2(PS2) have been found in early-onset familial forms of Alzheimer disease OBJECTIVE: To determine the cause of dementia in a family with early-onset illness. DESIGN, SETTING, AND PARTICIPANTS: A family with a history of dementia was referred to the Indiana Alzheimer Disease Center, Indianapolis. All the research in this study was done in a university or university hospital. The proband and her 4 siblings took part in the study. The proband, who is still alive, showed symptoms of Alzheimer disease at 38 years of age. Genomic DNA was obtained from blood samples of 5 family members. The APPandPS1genes of the proband were screened for mutations by amplification followed by direct sequencing. RESULTS: Sequence of exon 17 of the APPgene revealed a single nucleotide (guanine to cytosine) substitution in 1 allele, resulting in an amino acid change at codon 717 (valine to leucine). Each of the proband's siblings were tested for this mutation by direct sequencing. Two of the 4 were found to have the mutation; one of whom was recently clinically diagnosed at the age of 36 years. CONCLUSIONS: A novel mutation in the APPgene (V717L) has been found in a family with a history of dementia, beginning in the mid to late 30s. The age of onset in this family is earlier than most of the other families with Alzheimer disease who also have APPmutations. Arch Neurol. 2000.