Alzheimer Disease: Drachman DA

Drachman DA. · No affiliation provided · Neurology. · Pubmed #18458213 No free full text.

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Drachman DA. · Department of Neurology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. · Curr Neurol Neurosci Rep. · Pubmed #17618530 No free full text.

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Miller N, Drachman DA. · No affiliation provided · Neurology. · Pubmed #17130403 No free full text.

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Drachman DA. · No affiliation provided · Am J Alzheimers Dis Other Demen. · Pubmed #12083342 No free full text.

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Albert MS, Drachman DA. · No affiliation provided · Neurology. · Pubmed #10908884 No free full text.

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Drachman DA. · Department of Neurology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. · Neurology. · Pubmed #17060558 No free full text.

Abstract: Sporadic Alzheimer disease (AD) is related to advancing age far more than to any other risk factor and ultimately affects almost half of the population over age 85. Despite its remarkable prevalence among the elderly, it has been regarded as a specific disease, distinct from "normal aging." This view is supported in large part by clinical and pathologic similarities to early-onset, dominantly inherited familial AD, where genetic mutations related to beta-amyloid have been identified. There is much evidence that sporadic AD overlaps with normal aging in many clinical and pathologic features. Some of the many molecular age-related changes (ARCs) affecting the brain, both intrinsic (programmed) and extrinsic (stochastic), are reviewed, with discussion of the effects they have singly and collectively on neuronal viability and vulnerability. The effect of ARCs on the brain is seen as the biologic manifestation of increasing entropy, an approach that helps to explain the progressive decline of neural and cognitive function over time; the ability of multiple, varied ARCs to summate as individuals age; the transitional relationship between normal aging, mild cognitive impairment, and AD; and the apparent differences between normal aging and AD. Increasing entropy, manifest through a complex network of interacting ARCs, is seen as the fundamental driving cause of neural and cognitive decline in the elderly, as well as the overriding etiologic principle in further transition to sporadic AD. Research on sporadic AD has largely focused on finding a single causal metabolic disorder or genetic mutation. Multiple ARCs contribute to declining function and increased frailty in the aging brain, however, and to the catastrophic disintegration of sporadic AD. Effective prevention or treatment will depend on recognizing the contributions of a multiplicity of ARCs to AD and reducing the burden of as many as possible. The role of amyloid is seen as one element in the larger network of senescent changes involving the aging brain.

Drachman DA. · Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA. · Alzheimer Dis Assoc Disord. · Pubmed #16917191 No free full text.

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Swearer JM, O'Donnell BF, Parker M, Kane KJ, Drachman DA. · Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. · Am J Alzheimers Dis Other Demen. · Pubmed #11398564 No free full text.

Abstract: Persons at risk for inherited neurodegenerative diseases may experience symptoms of anxiety and depression because of concern over the possibility of developing the disease in the future. The purpose of this study was to assess psychological and emotional symptoms in persons at the age of risk for developing early-onset familial Alzheimer's disease (FAD). Their responses on a psychiatric rating scale (SCL-90-R) were compared with four groups: patients with mild FAD; head injury patients; patients with clinically diagnosed depression; and healthy control subjects. Mean scores of the at-risk FAD group were not statistically different than those of the controls. In contrast, the head injury and depressed groups had significantly elevated scores across the clinical scales. These results suggest that depression and anxiety are not prominent features in persons at genetic risk for early-onset familial Alzheimer's disease. Similar results have been found in studies of persons at risk for developing Huntington's disease, another autosomal dominant neurodegenerative disease.

Seshadri S, Zornberg GL, Derby LE, Myers MW, Jick H, Drachman DA. · Framingham Heart Study and Department of Neurology, Boston University School of Medicine, Boston, MA, USA. · Arch Neurol. · Pubmed #11255447 links to  free full text

Abstract: BACKGROUND: Previous studies have examined the relation between postmenopausal estrogen replacement therapy (ERT) and the risk of Alzheimer disease (AD). The findings have been inconsistent, since some studies have been interpreted as showing a protective effect while others have reported no effect. OBJECTIVE: To determine whether exposure to ERT is associated with a reduced risk of AD. DESIGN: Population-based nested case-control study. SETTING: The United Kingdom-based General Practice Research Database. PATIENTS: The base cohort consisted of women who were recipients of ERT (n = 112 481) and a similar cohort of women who did not use estrogens (n = 108 925). The 2 cohorts were restricted to women born on or before January 1, 1950. From the 2 cohorts, we identified and verified 59 newly diagnosed cases of AD and 221 matched control subjects. MAIN OUTCOME MEASURE: Prior and current use of ERT in cases compared with controls. RESULTS: Among the 59 newly diagnosed cases of AD, 15 (25%) were current estrogen users, while among the controls, 53 (24%) were current users. The adjusted odds ratio comparing all current estrogen recipients with nonrecipients was 1.18 (95% confidence interval, 0.59-2.37). In estrogen users who took the drug for 5 years or longer compared with nonusers, the odds ratio was 1.05 (95% confidence interval, 0.32-3.44). Odds ratios were similar for estrogen recipients who received estrogens alone and recipients who received combined estrogen-progestin treatment. CONCLUSION: The use of ERT in women after the onset of menopause was not associated with a reduced risk of developing AD.

Jick H, Zornberg GL, Jick SS, Seshadri S, Drachman DA. · Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, MA 02421, USA. · Lancet. · Pubmed #11089820 No free full text.

Abstract: BACKGROUND: Dementia affects an estimated 10% of the population older than 65 years. Because vascular and lipid-related mechanisms are thought to have a role in the pathogenesis of Alzheimer's disease and vascular dementia, we did an epidemiological study of the potential effect of HMGCoA (3 hydroxy-3methylglutaryl-coenzyme A) reductase inhibitors (statins) and other lipid-lowering agents on dementia. METHODS: We used a nested case-control design with information derived from 368 practices which contribute to the UK-based General Practice Research Database. The base study population included three groups of patients age 50 years and older: all individuals who had received lipid-lowering agents (LLAs); all individuals with a clinical diagnosis of untreated hyperlipidaemia; and a randomly selected group of other individuals. From this base population, all cases with a computer-recorded clinical diagnosis of dementia were identified. Each case was matched with up to four controls derived from the base population on age, sex, practice, and index date of case. FINDINGS: The study encompassed 284 cases with dementia and 1080 controls. Among controls 13% had untreated hyperlipidaemia, 11% were prescribed statins, 7% other LLAs, and 69% had no hyperlipidaemia or LLA exposure. The relative risk estimates of dementia adjusted for age, sex, history of coronary-artery disease, hypertension, coronary-bypass surgery and cerebral ischaemia, smoking and body mass index for individuals with untreated hyperlipidaemia (odds ratio 0.72 [95% CI 0.45-1.14]), or treated with nonstatin LLAs (0.96 [0.47-1.97], was close to 1.0 and not significant compared with people who had no diagnosis of hyperlipidaemia or exposure to other lipid-lowering drugs. The adjusted relative risk for those prescribed statins was 0.29 (0.13-0.63; p=0.002). INTERPRETATION: Individuals of 50 years and older who were prescribed statins had a substantially lowered risk of developing dementia, independent of the presence or absence of untreated hyperlipidaemia, or exposure to nonstatin LLAs. The available data do not distinguish between Alzheimer's disease and other forms of dementia.

Lippa CF, Swearer JM, Kane KJ, Nochlin D, Bird TD, Ghetti B, Nee LE, St George-Hyslop P, Pollen DA, Drachman DA. · Department of Neurology, Medical College of Pennsylvania-Hahnemann University, Philadelphia, PA, USA. · Ann Neurol. · Pubmed #10976645 No free full text.

Abstract: Alzheimer's disease (AD) is caused by multiple genetic and/or environmental etiologies. Because differences in the genetically determined pathogenesis may cause differences in the phenotype, we examined age at onset and age at death in 90 subjects with dominantly inherited AD due to different mutations (amyloid precursor protein, presenilin-1, and presenilin-2 genes). We found that among patients with dominantly inherited AD, genetic factors influence both age at onset and age at death.