L J Thal

University of California, San Diego, San Diego, California, United States

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Publications (402)2272.14 Total impact

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    ABSTRACT: Agitation and psychosis are common in Alzheimer disease and cause considerable morbidity. We attempted to delay or to prevent agitation and psychosis with the use of divalproex sodium (valproate). To determine whether treatment with valproate could delay or prevent emergence of agitation or psychosis. A multicenter, randomized, double-blind, placebo-controlled trial of flexible-dose valproate in 313 (of 513 screened) individuals with moderate Alzheimer disease who had not yet experienced agitation or psychosis. The study was conducted from November 1, 2005, through March 31, 2009, at 46 sites in the United States. Participants were randomly assigned to valproate treatment at a target dose of 10 to 12 mg per kilogram of body weight per day or identical-appearing placebo for 24 months followed by a 2-month period of single-blind placebo treatment. Time to emergence of clinically significant agitation or psychosis. A total of 122 participants (59 receiving valproate and 63 receiving placebo) completed 24 months of treatment while taking study medication; 42 (27 receiving valproate and 15 receiving placebo) reached 24 months having discontinued study medication; 150 reached month 26. There was no difference between groups in time to emergence of agitation or psychosis (Cox proportional hazard ratio, 0.96; P = .88). There was no difference between groups in change on any secondary outcome. The valproate group had higher rates of somnolence, gait disturbance, tremor, diarrhea, and weakness. Eighty-eight participants underwent magnetic resonance imaging scans at baseline and 12 months; the valproate group showed greater loss in hippocampal and whole-brain volume, accompanied by greater ventricular expansion (P < .001). Valproate treatment did not delay emergence of agitation or psychosis or slow cognitive or functional decline in patients with moderate Alzheimer disease and was associated with significant toxic effects.
    Archives of general psychiatry 08/2011; 68(8):853-61. · 12.26 Impact Factor
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    ABSTRACT: The article to which this erratum refers was published in Hum Brain Mapp 2010, DOI: 10.1002/hbm.20905. © 2010 Wiley-Liss, Inc.
    Human Brain Mapping 09/2010; · 6.88 Impact Factor
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    ABSTRACT: We applied the hippocampal radial atrophy mapping technique to the baseline and follow-up magnetic resonance image data of 169 amnestic mild cognitive impairment (MCI) participants in the imaging arm of the Alzheimer's Disease Cooperative Study MCI Donepezil/Vitamin E trial. Sixty percent of the subjects with none to mild hippocampal atrophy rated with the visual medial temporal atrophy rating scale (MTA score < 2) and 33.8% of the subjects with moderate to severe (MTA ≥ 2) hippocampal atrophy converted to Alzheimer's disease (AD) during 3-year follow-up. MTA ≥ 2 showed a trend for greater left sided hippocampal atrophy versus MTA < 2 groups at baseline (Pcorrected = 0.08). Higher MTA scores were associated with progressive atrophy of the subiculum and the CA1-3 subregions. The MTA < 2 group demonstrated significant bilateral atrophy progression at follow-up (left Pcorrected = 0.008; right Pcorrected = 0.05). Relative to MTA < 2 nonconverters, MTA < 2 converters showed further involvement of the subiculum and CA1 and additional involvement of CA2-3 at follow-up. Right CA1 atrophy was significantly associated with conversion to dementia (for 1 mm greater right CA1 radial distance subjects had 50% reduced hazard for conversion). Greater CA1 and subicular atrophy can be demonstrated early and is predictive of future conversion to AD, whereas CA2-3 involvement becomes more evident as the disease progresses. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.
    Human Brain Mapping 02/2010; 31(5):786 - 797. · 6.88 Impact Factor
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    ABSTRACT: Mild cognitive impairment (MCI) is a transitional state between normal cognitive functioning and dementia. A proposed MCI typology classifies individuals by the type and extent of cognitive impairment, yet few studies have characterized or compared these subtypes. Four hundred forty-seven women 65 years of age and older from the Women's Health Initiative Memory Study were classified into the 4 MCI subgroups and a "no impairment" group and compared on clinical, sociodemographic, and health variables. A cognitive deficit in at least 1 domain was present in 82.1% of participants, with most (74.3%) having deficits in multiple cognitive domains. Only 4.3% had an isolated memory deficit, whereas 21.3% had an isolated nonmemory deficit. Of the 112 women who met all MCI criteria examined, the most common subtype was amnestic multidomain MCI (42.8%), followed by nonamnestic multiple domain MCI (26.7%), nonamnestic single domain (24.1%), and amnestic single domain MCI (6.3%). Subtypes were similar with respect to education, health status, smoking, depression, and prestudy and onstudy use of hormone therapy. Despite the attention it receives in the literature, amnestic MCI is the least common type highlighting the importance of identifying and characterizing other nonamnestic and multidomain subtypes. Further research is needed on the epidemiology of MCI subtypes, clinical and biologic differences between them, and rates for conversion to dementia.
    Alzheimer disease and associated disorders 01/2010; 24(3):248-55. · 2.88 Impact Factor
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    ABSTRACT: The effects of AMPA lesions of the nucleus basalis magnocellularis (NBM) on EEG and event-related potentials (ERPs) generated by an auditory discrimination task were examined. The lesions significantly reduced choline acetyl transferase (ChAT) activity in frontal and parietal cortex. NBM lesions produced significantly more errors in the task. Significant increases in EEG spectral power in the fronto-parietal cortex were found, most predominantly in the higher frequencies (8-32 Hz), suggesting increases in arousal in the lesioned animals. Additionally, the lesion resulted in an increase in the area, the standard deviation of the amplitude of the N1 component, as well as instability in the amplitudes of several other ERP components. These results suggest that NBM lesions may impair ability to correctly respond in a discrimination task by a combination of increased arousal and an inability to maintain stable attentional capacity.
    07/2009; 96(1-2):23-44.
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    ABSTRACT: Immunization of patients with Alzheimer's disease (AD) with synthetic amyloid-beta peptide (Abeta(42)) (AN1792) was previously studied in a randomized, double-blind, placebo-controlled phase 2a clinical trial, Study AN1792(QS-21)-201. Treatment was discontinued following reports of encephalitis. One year follow-up revealed that AN1792 antibody responders showed improvements in cognitive measures as assessed by the neuropsychological test battery (NTB) and a decrease in brain volume compared with placebo. A follow-up study, Study AN1792(QS-21)-251, was conducted to assess the long-term functional, psychometric, neuroimaging, and safety outcomes of patients from the phase 2a study 4.6 years after immunization with AN1792. The results were analyzed by comparing patients originally identified as antibody responders in the AN1792 phase 2a study with placebo-treated patients. One hundred and fifty-nine patients/caregivers (30 placebo; 129 AN1792) participated in this follow-up study. Of the 129 AN1792-treated patients, 25 were classified in the phase 2a study as antibody responders (anti-AN1792 titers > or = 1:2,200 at any time after the first injection). Low but detectable, sustained anti-AN1792 titers were found in 17 of 19 samples obtained from patients classified as antibody responders in the phase 2a study. No detectable anti-AN1792 antibodies were found in patients not classified as antibody responders in the phase 2a study. Significantly less decline was observed on the Disability Assessment for Dementia scale among antibody responders than placebo-treated patients (p=0.015) after 4.6 years. Significant differences in favor of responders were also observed on the Dependence Scale (p=0.033). Of the small number of patients who underwent a follow-up MRI, antibody responders showed similar brain volume loss during the follow-up period subsequent to the AN1792 phase 2a study compared with placebo-treated patients. Approximately 4.6 years after immunization with AN1792, patients defined as responders in the phase 2a study maintained low but detectable, sustained anti-AN1792 antibody titers and demonstrated significantly reduced functional decline compared with placebo-treated patients. Brain volume loss in antibody responders was not significantly different from placebo-treated patients approximately 3.6 years from the end of the original study. No further cases of encephalitis were noted. These data support the hypothesis that Abeta immunotherapy may have long-term functional benefits.
    Current Alzheimer research 05/2009; 6(2):144-51. · 4.97 Impact Factor
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    ABSTRACT: Dementia with Lewy bodies (DLB) is often characterized by pronounced impairment in visuospatial skills, attention, and executive functions. However, the strength of the phenotypic expression of DLB varies and may be weaker in patients with extensive concomitant Alzheimer's disease (AD). To determine whether strength of the DLB clinical phenotype impacts cognitive decline, visuospatial and language tests were retrospectively used to predict 2-year rate of global cognitive decline in 22 autopsy-confirmed DLB patients (21 with concomitant AD) and 44 autopsy-confirmed "pure" AD patients. Generalized estimating equations (GEE) revealed a significant interaction such that poor baseline performances on tests of visuospatial skills were strongly associated with a rapid rate of cognitive decline in DLB but not AD (p < .001). No effect of confrontation naming was found. DLB patients with poor visuospatial skills had fewer neurofibrillary tangles and were more likely to experience visual hallucinations than those with better visuospatial skills. These results suggest that the severity of visuospatial deficits in DLB may identify those facing a particularly malignant disease course and may designate individuals whose clinical syndrome is impacted more by Lewy body formation than AD pathology.
    Neuropsychology 11/2008; 22(6):729-37. · 3.58 Impact Factor
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    ABSTRACT: White matter hyperintensities (WMH) have an effect on cognition and are increased in severity among individuals with amnestic mild cognitive impairment (aMCI). The influence of WMH on progression of aMCI to Alzheimer's disease (AD) is less clear. Data were drawn from a three-year prospective, double blind, placebo controlled clinical trial that examined the effect of donepezil or vitamin E on progression from aMCI to AD. WMH from multiple brain regions were scored on MR images obtained at entry into the trial from a subset of 152 study participants using a standardized visual rating scale. Cox proportional hazards models adjusting for age, education and treatment arm were used to investigate the role of WMH on time to progression. 55 of the 152 (36.2 %) aMCI subjects progressed to AD. Only periventricular hyperintensities (PVH) were related to an increased risk of AD within three years (HR = 1.59, 95 % CI = 1.24 - 2.05, p-value < 0.001). Correcting for medial temporal lobe atrophy or the presence of lacunes did not change statistical significance. PVH are associated with an increased risk of progression from aMCI to AD. This suggests that PVH, an MRI finding thought to represent cerebrovascular damage, contributes to AD onset in vulnerable individuals independent of Alzheimer pathology.
    Journal of Neurology 10/2008; 255(9):1302-8. · 3.58 Impact Factor
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    ABSTRACT: 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. To determine the efficacy and safety of B vitamin supplementation in the treatment of AD. 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. 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. Change in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog). 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. This regimen of high-dose B vitamin supplements does not slow cognitive decline in individuals with mild to moderate AD. clinicaltrials.gov Identifier: NCT00056225.
    JAMA The Journal of the American Medical Association 10/2008; 300(15):1774-83. · 29.98 Impact Factor
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    ABSTRACT: The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study. The objective of this study was to evaluate the effect of treatment on MRI atrophy rates; and validate rate measures from serial MRI as indicators of disease progression in multi center therapeutic trials for MCI. Annual percent change (APC) from baseline to follow-up was measured for hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects who remained in the treatment study and completed technically satisfactory baseline and follow-up scans. Although a non-significant trend toward slowing of hippocampal atrophy rates was seen in APOE is an element of 4 carriers treated with donepezil; no treatment effect was confirmed for any MRI measure in either treatment group. For each of the four brain atrophy rate measures, APCs were greater in subjects who converted to AD than non-converters, and were greater in APOE is an element of 4 carriers than non-carriers. MRI APCs and changes in cognitive test performance were uniformly correlated in the expected direction (all p<0.000). Results of this study support the feasibility of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI.
    Neurobiology of aging 09/2008; 29(9):1285-95. · 5.94 Impact Factor
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    ABSTRACT: To evaluate the safety, tolerability, and amyloid beta (Abeta) response to the gamma-secretase inhibitor LY450139 in Alzheimer disease. Multicenter, randomized, double-blind, dose-escalation, placebo-controlled trial. Community-based clinical research centers. Patients Fifty-one individuals with mild to moderate Alzheimer disease were randomized to receive placebo (n=15) or LY450139 (100 mg [n=22] or 140 mg [n=14]), with 43 completing the treatment phase. Intervention The LY450139 groups received 60 mg/d for 2 weeks, then 100 mg/d for 6 weeks, and then either 100 or 140 mg/d for 6 additional weeks. Primary outcome measures were adverse events, plasma and cerebrospinal fluid Abeta levels, vital signs, electrocardiographic data, and laboratory safety test results. Secondary outcome measures included the Alzheimer's Disease Assessment Scale cognitive subscale and the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale. Group differences were seen in skin and subcutaneous tissue concerns (P=.05), including 3 possible drug rashes and 3 reports of hair color change in the treatment groups. There were 3 adverse event-related discontinuations, including 1 transient bowel obstruction. The plasma Abeta(40) concentration was reduced by 58.2% for the 100-mg group and 64.6% for the 140-mg group (P<.001). No significant reduction was seen in cerebrospinal fluid Abeta levels. No group differences were seen in cognitive or functional measures. LY450139 was generally well tolerated at doses of up to 140 mg/d for 14 weeks, with several findings indicating the need for close clinical monitoring in future studies. Decreases in plasma Abeta concentrations were consistent with inhibition of gamma-secretase. Trial Registration clinicaltrials.gov Identifier: NCT00244322.
    Archives of neurology 08/2008; 65(8):1031-8. · 7.58 Impact Factor
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    ABSTRACT: The association between the APOE epsilon4 allele and depression was investigated in a retrospective study of 323 AD patients. Patients were divided into demographically comparable groups based on the presence or absence of depression. Results showed that the frequency of APOE epsilon4 allele was significantly higher in the depressed vs non-depressed AD patients (72% and 58%, respectively), and an interaction revealed that women possessing the APOE epsilon4 allele were almost four times more likely to be depressed than those without the epsilon4 allele. Results are consistent with recent suggestions that the APOE epsilon4 genotype may be over-represented among depressed women with AD and highlight the need for additional research investigating the links between APOE genotype, mood, and gender.
    International Journal of Geriatric Psychiatry 07/2008; 23(6):632-6. · 2.98 Impact Factor
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    ABSTRACT: Cognitive-discrepancy analysis has been shown to be a useful technique for detecting subtle cognitive deficits in normal-functioning elderly individuals who are genetically at-risk for Alzheimer disease (AD). However, studies that have used cognitive-discrepancy measures to date have used retrospective or cross-sectional designs, and the utility of this approach to predict cognitive decline has not been examined in a prospective investigation. Longitudinal study. San Diego, CA, Veterans Administration Hospital. Twenty-four normal-functioning elderly individuals participated in the study, with 16 subjects exhibiting no change in their Dementia Rating Scale (DRS) scores over an 1-year period (Stable Group), and 8 subjects exhibiting a decline in DRS scores over the 1-year period (Decline group). A cognitive-discrepancy measure isolating cognitive switching was computed that contrasted performance on a new higher-level task of executive functioning (a Stroop/Switching measure) relative to a composite measure of lower-level Stroop conditions. a) In the year before their cognitive changes, the Decline group exhibited a significantly larger cognitive-discrepancy (Stroop/Switching versus lower-level Stroop conditions) score compared with a control (Stable) group; and b) the cognitive-discrepancy measure was superior to APOE genotype in predicting DRS decline. Cognitive-discrepancy analysis isolating a component executive function ability not only seems to be a useful tool for identifying individuals at risk for cognitive deficits, but also shows promise in predicting individuals who may show subtle cognitive decline over time.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 06/2008; 16(5):366-74. · 3.35 Impact Factor
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    ABSTRACT: Late-onset Alzheimer's disease (LOAD) and Parkinson's disease (PD) are the most common neurodegenerative disorders and in both diseases susceptibility is known to be influenced by genes. We set out to identify novel susceptibility genes for LOAD by performing a large scale, multi-tiered association study testing 4692 single nucleotide polymorphism (SNPs). We identified a SNP within a putative transcription factor binding site in the NEDD9 gene (neural precursor cell expressed, developmentally down-regulated), that shows good evidence of association with disease risk in four out of five LOAD samples [N = 3521, P = 5.38x10(-6), odds ratio (OR) = 1.38 (1.20-1.59)] and in addition, we observed a similar pattern of association in two PD sample sets [N = 1464, P = 0.0145, OR =1.31 (1.05-1.62)]. In exploring a potential mechanism for the association, we observed that expression of NEDD9 and APOE show a strong inverse correlation in the hippocampus of Alzheimer's cases. These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD.
    Human Molecular Genetics 04/2008; 17(5):759-67. · 7.69 Impact Factor
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    ABSTRACT: A recent clinical trial in patients with Mild Cognitive Impairment (MCI) found an increased rate of possible or probable Alzheimer's disease (AD) diagnoses in patients assigned to rofecoxib compared to placebo. This unexpected finding was difficult to interpret due to methodological issues and a lack of confirmation on secondary endpoints, as well as a lack of confirmation in trials in related populations. We performed additional post hoc analyses to explore explanations for the finding based on possible neuropathological, cardiovascular/cerebrovascular, or cognitive effects of rofecoxib. 1) Neuropathological hypothesis: Of the 189 incident cases of possible or probable AD, 154 were probable AD. In probable AD patients, the treatment hazard ratio was reduced compared to the primary analysis -- a concordant finding would have strengthened a conclusion that rofecoxib accelerated the underlying neuropathology of AD. The treatment hazard ratio was increased in the remaining 35 patients with less certain diagnoses, but there was no single predominant reason for the reduced certainty of diagnosis. 2) Cardiovascular hypothesis: Neither cardiovascular risk status nor mean arterial blood pressure had an overall effect on AD diagnosis or modified the treatment difference. 3) Cognitive side-effects hypothesis: The percentages of patients with non-specific NSAID-type central nervous system adverse events were similar between the treatment groups. In summary, the present analyses are limited by their post hoc nature but provided little support for any of the possible explanations explored. The significance of the observation that rofecoxib increased the rate of conversion from MCI to AD remains uncertain.
    Current Alzheimer Research 03/2008; 5(1):73-82. · 3.68 Impact Factor
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    ABSTRACT: To compare volumetric MRI of whole brain and medial temporal lobe structures to clinical measures for predicting progression from amnestic mild cognitive impairment (MCI) to Alzheimer disease (AD). Baseline MRI scans from 129 subjects with amnestic MCI were obtained from participants in the Alzheimer's Disease Cooperative Study group's randomized, placebo-controlled clinical drug trial of donepezil, vitamin E, or placebo. Measures of whole brain, ventricular, hippocampal, and entorhinal cortex volumes were acquired. Participants were followed with clinical and cognitive evaluations until formal criteria for AD were met, or completion of 36 months of follow-up. Logistic regression modeling was done to assess the predictive value of all MRI measures, risk factors such as APOE genotype, age, family history of AD, education, sex, and cognitive test scores for progression to AD. Least angle regression modeling was used to determine which variables would produce an optimal predictive model, and whether adding MRI measures to a model with only clinical measures would improve predictive accuracy. Of the four MRI measures evaluated, only ventricular volumes and hippocampal volumes were predictive of progression to AD. Maximal predictive accuracy using only MRI measures was obtained by hippocampal volumes by themselves (60.4%). When clinical variables were added to the model, the predictive accuracy increased to 78.8%. Use of MRI measures did not improve predictive accuracy beyond that obtained by cognitive measures alone. APOE status, MRI, or demographic variables were not necessary for the optimal predictive model. This optimal model included the Delayed 10-word list recall, New York University Delayed Paragraph Recall, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale total score. In moderate stages of amnestic mild cognitive impairment, common cognitive tests provide better predictive accuracy than measures of whole brain, ventricular, entorhinal cortex, or hippocampal volumes for assessing progression to Alzheimer disease.
    Neurology 02/2008; 70(3):191-9. · 8.25 Impact Factor
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    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, homo- cysteine levels can be reduced by administration of high-dose supplements of folic acid and vitamins B6 and B12. Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline.
    01/2008;
  • Alzheimers & Dementia - ALZHEIMERS DEMENT. 01/2008; 4(4).

Publication Stats

21k Citations
2,272.14 Total Impact Points

Institutions

  • 1991–2013
    • University of California, San Diego
      • • Department of Neurosciences
      • • Department of Psychiatry
      • • Division of Neurosurgery
      • • Department of Medicine
      San Diego, California, United States
  • 2010
    • Wake Forest School of Medicine
      • Department of Psychiatry and Behavioral Medicine
      Winston-Salem, NC, United States
  • 2005–2008
    • VA San Diego Healthcare System
      San Diego, California, United States
    • University of California, San Francisco
      San Francisco, California, United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
    • University Center Rochester
      • Department of Psychiatry
      Rochester, Minnesota, United States
    • Tel Aviv University
      • Department of Human Molecular Genetics and Biochemistry
      Tel Aviv, Tel Aviv, Israel
    • Banner Sun Health Research Institute
      Sun City, Arizona, United States
  • 2002–2008
    • Mayo Foundation for Medical Education and Research
      • • Department of Radiology
      • • Department of Neurology
      Scottsdale, AZ, United States
  • 2007
    • University of Rochester
      Rochester, New York, United States
  • 1999–2006
    • University of Washington Seattle
      • • Department of Neurology
      • • Department of Psychosocial & Community Health
      Seattle, WA, United States
  • 1997–2006
    • New York University
      • • Alzheimer’s Disease Center
      • • Department of Neurology
      New York City, NY, United States
    • University of Kentucky
      Lexington, Kentucky, United States
  • 2000–2005
    • Georgetown University
      • Department of Neurology
      Washington, Washington, D.C., United States
    • Ospedali Riuniti di Bergamo
      Bérgamo, Lombardy, Italy
    • University of California, Irvine
      Irvine, California, United States
    • University of Iowa
      • Department of Psychiatry
      Iowa City, IA, United States
    • Asan Medical Center
      • Department of Neurology
      Seoul, Seoul, South Korea
  • 1995–2005
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2004
    • University of California, Los Angeles
      • Department of Neurology
      Los Angeles, CA, United States
    • Azienda Ospedaliera Niguarda Ca' Granda
      Milano, Lombardy, Italy
  • 2000–2004
    • University of Bologna
      • School of Medicine
      Bologna, Emilia-Romagna, Italy
  • 1997–2004
    • Mount Sinai School of Medicine
      • Department of Psychiatry
      Manhattan, NY, United States
  • 2003
    • Oregon Health and Science University
      • Department of Psychiatry
      Portland, OR, United States
  • 1997–2003
    • CSU Mentor
      Long Beach, California, United States
  • 1988–2003
    • Naval Medical Center San Diego
      San Diego, California, United States
  • 2000–2002
    • University of Texas Southwestern Medical Center
      • Department of Psychiatry
      Dallas, TX, United States
  • 1997–2000
    • Salk Institute
      • Laboratory of Genetics
      La Jolla, CA, United States
  • 1996–1997
    • Columbia University
      • Gertrude H. Sergievsky Center
      New York City, New York, United States
  • 1994
    • Johns Hopkins University
      • Department of Neurology
      Baltimore, MD, United States
  • 1993
    • San Diego State University
      • Department of Psychology
      San Diego, CA, United States
    • Spokane VA Medical Center
      Spokane, Washington, United States
  • 1989–1990
    • Fairfield University
      Fairfield, Connecticut, United States
  • 1978–1988
    • Albert Einstein College of Medicine
      • Department of Neuroradiology
      New York City, NY, United States