Alzheimer Disease: Diaz-Arrastia R

Diaz-Arrastia R, Baskin F. · No affiliation provided · Arch Neurol. · Pubmed #11255437 links to  free full text

This publication has no abstract.

Diaz-Arrastia R, Gong Y, Fair S, Scott KD, Garcia MC, Carlile MC, Agostini MA, Van Ness PC. · Department of Neurology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. · Arch Neurol. · Pubmed #12810485 links to  free full text

Abstract: BACKGROUND: Late posttraumatic seizures are a common complication of moderate and severe traumatic brain injury. Inheritance of the apolipoprotein E (APOE) epsilon4 allele is associated with increased risk of Alzheimer disease, progression to disability in multiple sclerosis, and poor outcome after traumatic brain injury. OBJECTIVE: To determine whether inheritance of APOE epsilon4 is associated with increased risk of developing late posttraumatic seizures. DESIGN: Prospective study. SETTING: Neurosurgical service at an urban level I trauma center.Patients Patients admitted with a diagnosis of moderate and severe traumatic brain injury were enrolled. METHODS: Six months after injury, patients were contacted to determine functional outcome (according to the Glasgow Outcome Scale-Expanded [GOS-E]) and the presence of late posttraumatic seizures. Genotype at the APOE locus was determined by restriction fragment length polymorphism analysis. RESULTS: DNA and outcome information was obtained from 106 subjects. Six months after injury, 31 (29%) had a poor outcome (GOS-E score, 1-4), 47 (44%) had an intermediate outcome (GOS-E score, 5-6), and 28 (26%) had a favorable outcome (GOS-E score, 7-8). Twenty-one patients (20%) had at least 1 late posttraumatic seizure. The relative risk of late posttraumatic seizures for patients with the epsilon4 allele was 2.41 (95% confidence interval, 1.15-5.07; P =.03). In this cohort, inheritance of APOE epsilon4 was not associated with an unfavorable GOS-E score 6 (P =.47). CONCLUSIONS: Inheritance of the APOE epsilon4 allele is associated with increased risk of late posttraumatic seizures. In this cohort, this risk appears to be independent of an effect of epsilon4 on functional outcome. A better understanding of the molecular role of APOE in neurodegenerative diseases may be helpful in developing antiepileptogenic therapies.

Aisen PS, Egelko S, Andrews H, Diaz-Arrastia R, Weiner M, DeCarli C, Jagust W, Miller JW, Green R, Bell K, Sano M. · Department of Neurology, Georgetown University Medical Center, Washington, DC 20007, USA. · Am J Geriatr Psychiatry. · Pubmed #12611755 No free full text.

Abstract: OBJECTIVE: Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease (AD). METHODS: Authors used an open-label trial of folic acid, vitamin B(12), and vitamin B(6), in combination for 8 weeks, with measurement of plasma homocysteine levels in the fasting state and after methionine-loading. A total of 69 subjects with AD were enrolled, including 33 who were taking standard multivitamin supplements; 66 were available at 8-week follow-up. RESULTS: The high-dose vitamin regimen was associated with a significant reduction in fasting and post-methionine-loading homocysteine. Reductions were greater in the subgroup not using multivitamins, but were also significant in the multivitamin users. CONCLUSION: High-dose vitamin supplementation reduces homocysteine levels in patients with AD. The effect of supplementation on rate of cognitive decline will be assessed later in a randomized, double-blind study.

Richardson JR, Shalat SL, Buckley B, Winnik B, O'Suilleabhain P, Diaz-Arrastia R, Reisch J, German DC. · Robert Wood Johnson Medical School, Piscataway, New Jersey, USA. · Arch Neurol. · Pubmed #19597089 No free full text.

Abstract: BACKGROUND: Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. OBJECTIVE: To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. DESIGN: Case-control study. SETTING: An academic medical center. PARTICIPANTS: Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. MAIN OUTCOME MEASURES: Levels of 16 organochlorine pesticides in serum samples. RESULTS: beta-Hexachlorocyclohexane (beta-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of beta-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of beta-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67-11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum beta-HCH and PD. CONCLUSIONS: These data suggest that beta-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of beta-HCH as a etiologic agent for some cases of PD.

Weiner MF, de la Plata CM, Fields BA, Womack KB, Rosenberg RN, Gong YH, Qu BX, Diaz-Arrastia R, Hynan LS. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9129, USA. · Curr Alzheimer Res. · Pubmed #19199875 No free full text.

Abstract: We obtained brain MRIs, plasma homocysteine levels and apolipoprotein E genotyping for 11 American Indian Alzheimer disease (AD) subjects and 10 Indian controls. We calculated white matter hyperintensity volume (WMHV), whole brain volume (WBV), and ratio of white matter hyperintensity volume to whole brain volume (WMHV/WBV). There were no significant differences between AD subjects and controls in gender, history of hypertension, diabetes, or history of high cholesterol, but hypertension and diabetes were more common among AD subjects. There was no difference between AD and control groups in age (range for all subjects was 61-89 years), % Indian heritage, waist size or body mass index. Median Indian heritage was 50% or greater in both groups. Range of education was 5-13 years in the AD group and 12-16 years in controls. Median plasma homocysteine concentration was higher in AD subjects (11 micromol/L vs. 9.8 micromol/L), but did not achieve statistical significance. Significantly more AD subjects had apolipoprotein Eepsilon4 alleles than did controls (63% vs.10%). Neuroimaging findings were not significantly different between the 2 groups, but AD subjects had greater WMHV (median 15.64 vs. 5.52 cc) and greater WMHV/WBV ratio (median 1.63 vs. 0.65 %) and a far greater range of WMHV. In combined AD subjects and controls, WBV correlated with BMI and age. WMHV and WMHV/WBV correlated inversely with MMSE scores (p = 0.001, 0.002, respectively). In addition, WMHV correlated positively with % Indian heritage (p = 0.047).

Aisen PS, Schneider LS, Sano M, Diaz-Arrastia R, van Dyck CH, Weiner MF, Bottiglieri T, Jin S, Stokes KT, Thomas RG, Thal LJ, Anonymous00042. · Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr, M/C 0949, La Jolla, CA 92093, USA. · JAMA. · Pubmed #18854539 links to  free full text

Abstract: CONTEXT: Blood levels of homocysteine may be increased in Alzheimer disease (AD) and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, homocysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B(6) and B(12). Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline. OBJECTIVE: To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, double-blind controlled clinical trial of high-dose folate, vitamin B(6), and vitamin B(12) supplementation in 409 (of 601 screened) individuals with mild to moderate AD (Mini-Mental State Examination scores between 14 and 26, inclusive) and normal folic acid, vitamin B(12), and homocysteine levels. The study was conducted between February 20, 2003, and December 15, 2006, at clinical research sites of the Alzheimer Disease Cooperative Study located throughout the United States. INTERVENTION: Participants were randomly assigned to 2 groups of unequal size to increase enrollment (60% treated with high-dose supplements [5 mg/d of folate, 25 mg/d of vitamin B(6), 1 mg/d of vitamin B(12)] and 40% treated with identical placebo); duration of treatment was 18 months. MAIN OUTCOME MEASURE: Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). RESULTS: A total of 340 participants (202 in active treatment group and 138 in placebo group) completed the trial while taking study medication. Although the vitamin supplement regimen was effective in reducing homocysteine levels (mean [SD], -2.42 [3.35] in active treatment group vs -0.86 [2.59] in placebo group; P < .001), it had no beneficial effect on the primary cognitive measure, rate of change in ADAS-cog score during 18 months (0.372 points per month for placebo group vs 0.401 points per month for active treatment group, P = .52; 95% confidence interval of rate difference, -0.06 to 0.12; based on the intention-to-treat generalized estimating equations model), or on any secondary measures. A higher quantity of adverse events involving depression was observed in the group treated with vitamin supplements. CONCLUSION: This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056225.

German DC, Gurnani P, Nandi A, Garner HR, Fisher W, Diaz-Arrastia R, O'Suilleabhain P, Rosenblatt KP. · Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9070, USA. · Biomed Pharmacother. · Pubmed #17614251 No free full text.

Abstract: For Alzheimer's disease (AD), the most common neurodegenerative disease, there is no simple, cost-effective biomarker for disease identification. Using novel mass spectrometry (MS)-based techniques, and analysis of the albumin-enriched low molecular weight proteome, minute amounts of human serum were analyzed for the measurement of thousands of peptides and proteins in parallel. The mass spectrograms were then evaluated with a novel computer algorithm to identify spectral peaks that discriminate between samples from patients with and without AD. There are four peaks that distinguish AD from control subjects and AD subjects from those with Parkinson's disease (PD). Additionally, after analyzing data from a recently published study of AD and control subjects, we found three discriminating peaks in common with the four from our patient serum samples. The identification of these peptides/proteins, and their direct measurement in patient serum, may allow the development of a simple, cost-effective test for AD.

Bhargava D, Weiner MF, Hynan LS, Diaz-Arrastia R, Lipton AM. · Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA. · J Geriatr Psychiatry Neurol. · Pubmed #16690992 No free full text.

Abstract: Two hundred forty-seven patients with early Alzheimer's disease were studied for the association of demographic, functional, and cognitive status and vascular comorbidities and risk factors present at index visit to rate of clinical disease progression over 3 years and to survival time. Patients who progressed to the moderate stage were designated fast progressors; those who remained in the early stage were designated slow progressors. At index visit, Mini-Mental State Exam score was significantly lower for the fast than the slow group; global impairment was significantly higher for the fast group. Cognitive scores showed greater annual decline in the fast group, and the fast group also had a greater annualized global change. The fast group had a shorter median survival time from onset, but age at onset, age at initial visit, history of heart problems, myocardial infarct, stroke, hypertension, diabetes, or past or current smoking did not differ between groups.

Gurol ME, Irizarry MC, Smith EE, Raju S, Diaz-Arrastia R, Bottiglieri T, Rosand J, Growdon JH, Greenberg SM. · Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA. · Neurology. · Pubmed #16401840 No free full text.

Abstract: BACKGROUND: Microvascular brain injury, typically measured by extent of white matter hyperintensity (WMH) on MRI, is an important contributor to cognitive impairment in the elderly. Recent studies suggest a role for circulating beta-amyloid peptide in microvascular dysfunction and white matter disease. METHODS: The authors performed a cross-sectional study of clinical, biochemical, and genetic factors associated with WMH in 54 subjects with Alzheimer disease (AD) or mild cognitive impairment (AD/MCI) and an independent group of 42 subjects with cerebral amyloid angiopathy (CAA). Extent of WMH was determined by computer-assisted volumetric measurement normalized to intracranial size (nWMH). Biochemical measurements included plasma concentrations of the 40- and 42-amino acid species of beta-amyloid (Abeta40 and Abeta42) detected by specific enzyme-linked immunosorbent assays. RESULTS: Plasma Abeta40 concentrations were associated with nWMH in both groups (correlation coefficient = 0.48 in AD/MCI, 0.42 in CAA, p < or = 0.005). Plasma Abeta40 remained independently associated with nWMH after adjustment for potential confounders among age, hypertension, diabetes, homocysteine, creatinine, folate, vitamin B12, and APOE genotype. The presence of lacunar infarctions was also associated with increased Abeta40 in both groups. nWMH was greater in CAA (19.8 cm3) than AD (11.1 cm3) or MCI (10.0 cm3; p < 0.05 for both comparisons). CONCLUSIONS: Plasma beta-amyloid 40 concentration is independently associated with extent of white matter hyperintensity in subjects with Alzheimer disease, mild cognitive impairment, or cerebral amyloid angiopathy. If confirmed in longitudinal studies, these data would suggest circulating beta-amyloid peptide as a novel biomarker or risk factor for microvascular damage in these common diseases of the elderly.

Irizarry MC, Gurol ME, Raju S, Diaz-Arrastia R, Locascio JJ, Tennis M, Hyman BT, Growdon JH, Greenberg SM, Bottiglieri T. · The Massachusetts Alzheimer Disease Research Center, Massachusetts General Hospital, Boston, MA, USA. · Neurology. · Pubmed #16275827 No free full text.

Abstract: BACKGROUND: Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (Abeta) metabolism, implicated in neurodegenerative diseases. OBJECTIVE: To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD). METHODS: Plasma tHcy, folate, vitamin B(12), creatinine, and Abeta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88). RESULTS: The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma Abeta levels even after adjustments for age and creatinine (p < 0.0001). CONCLUSIONS: Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma Abeta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD.