L J Thal

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi The Alzheimer's Disease Cooperative Study in 2004
    Leon J Thal
    Department of Neurosciences, University of California San Diego, La Jolla, CA 92093-0624, USA
    Alzheimer Dis Assoc Disord 18:183-5. 2004
  2. ncbi Therapeutics and mild cognitive impairment: current status and future directions
    Leon J Thal
    Department of Neuroscience, University of California, San Diego School of Medicine, La Jolla, California 92093, USA
    Alzheimer Dis Assoc Disord 17:S69-71. 2003
  3. ncbi Prevention of Alzheimer disease
    Leon J Thal
    Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0624, USA
    Alzheimer Dis Assoc Disord 20:S97-9. 2006
  4. ncbi Estrogen levels do not correlate with improvement in cognition
    Leon J Thal
    Department of Neurosciences, University of California, San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093, USA
    Arch Neurol 60:209-12. 2003
  5. ncbi A 1-year controlled trial of acetyl-l-carnitine in early-onset AD
    L J Thal
    Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA 92093 0624, USA
    Neurology 55:805-10. 2000
  6. ncbi Idebenone treatment fails to slow cognitive decline in Alzheimer's disease
    L J Thal
    Department of Neurosciences, University of California San Diego School of Medicine, La Jolla 92093 0624, USA
    Neurology 61:1498-502. 2003
  7. ncbi E4 allele dosage does not predict cholinergic activity or synapse loss in Alzheimer's disease
    J Corey-Bloom
    Department of Neurosciences, University of California, San Diego, La Jolla, USA
    Neurology 54:403-6. 2000
  8. ncbi Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment
    A S Fleisher
    Department of Neurosciences, University of California, San Diego, CA, USA
    Neurology 70:191-9. 2008
  9. ncbi Correlation of nicotinic receptor binding with clinical and neuropathological changes in Alzheimer's disease and dementia with Lewy bodies
    M N Sabbagh
    Department of Neurosciences, UCSD, La Jolla, CA, USA
    J Neural Transm 108:1149-57. 2001
  10. ncbi Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment
    A S Fleisher
    Alzheimer s Disease Cooperative Study, La Jolla, CA 92037, USA
    Neurology 68:1588-95. 2007

Research Grants

  1. GENE THERAPY OF BASAL FOREBRAIN CHOLINERGIC LESIONS
    Leon Thal; Fiscal Year: 2004
  2. Alzheimer's Disease Research Center Conference
    Leon Thal; Fiscal Year: 2006

Detail Information

Publications98

  1. ncbi The Alzheimer's Disease Cooperative Study in 2004
    Leon J Thal
    Department of Neurosciences, University of California San Diego, La Jolla, CA 92093-0624, USA
    Alzheimer Dis Assoc Disord 18:183-5. 2004
  2. ncbi Therapeutics and mild cognitive impairment: current status and future directions
    Leon J Thal
    Department of Neuroscience, University of California, San Diego School of Medicine, La Jolla, California 92093, USA
    Alzheimer Dis Assoc Disord 17:S69-71. 2003
  3. ncbi Prevention of Alzheimer disease
    Leon J Thal
    Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0624, USA
    Alzheimer Dis Assoc Disord 20:S97-9. 2006
    ....
  4. ncbi Estrogen levels do not correlate with improvement in cognition
    Leon J Thal
    Department of Neurosciences, University of California, San Diego, School of Medicine, 9500 Gilman Dr, La Jolla, CA 92093, USA
    Arch Neurol 60:209-12. 2003
    ..To investigate whether an association exists between estradiol and estrone levels and measures of cognitive functioning in women with Alzheimer disease (AD) treated with conjugated equine estrogen (Premarin; Wyeth-Ayerst, Philadelphia, Pa)...
  5. ncbi A 1-year controlled trial of acetyl-l-carnitine in early-onset AD
    L J Thal
    Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, CA 92093 0624, USA
    Neurology 55:805-10. 2000
    ..To determine the efficacy of acetyl-l-carnitine (ALCAR) on the rate of decline in early-onset AD patients...
  6. ncbi Idebenone treatment fails to slow cognitive decline in Alzheimer's disease
    L J Thal
    Department of Neurosciences, University of California San Diego School of Medicine, La Jolla 92093 0624, USA
    Neurology 61:1498-502. 2003
    ..To determine the effect of idebenone on the rate of decline in Alzheimer's disease (AD)...
  7. ncbi E4 allele dosage does not predict cholinergic activity or synapse loss in Alzheimer's disease
    J Corey-Bloom
    Department of Neurosciences, University of California, San Diego, La Jolla, USA
    Neurology 54:403-6. 2000
    ..To investigate the relationship between apolipoprotein E (APOE) genotype and both cholinergic dysfunction and synapse loss in AD...
  8. ncbi Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment
    A S Fleisher
    Department of Neurosciences, University of California, San Diego, CA, USA
    Neurology 70:191-9. 2008
    ..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)...
  9. ncbi Correlation of nicotinic receptor binding with clinical and neuropathological changes in Alzheimer's disease and dementia with Lewy bodies
    M N Sabbagh
    Department of Neurosciences, UCSD, La Jolla, CA, USA
    J Neural Transm 108:1149-57. 2001
    ..Loss of nAChR activity does not appear to be related to plaques or NFTs in AD or DLB...
  10. ncbi Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment
    A S Fleisher
    Alzheimer s Disease Cooperative Study, La Jolla, CA 92037, USA
    Neurology 68:1588-95. 2007
    ..To investigate the neurocognitive measures that best predict progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD)...
  11. ncbi Anosmia is very common in the Lewy body variant of Alzheimer's disease
    J M Olichney
    Alzheimer s Disease Research Center, University of California, San Diego, CA, USA
    J Neurol Neurosurg Psychiatry 76:1342-7. 2005
    ..Olfactory abnormalities are reported in Alzheimer's disease and Parkinson's disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer's disease...
  12. ncbi Abeta1-42 promotes cholinergic sprouting in patients with AD and Lewy body variant of AD
    E Masliah
    Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093 0624, USA emasliah ucsd edu
    Neurology 61:206-11. 2003
    ....
  13. ncbi Prevalence of symptoms on the CERAD behavior rating scale for dementia in normal elderly subjects and Alzheimer's disease patients
    R E Tractenberg
    Department of Neurosciences, University of California, San Diego 92093 0949, USA
    J Neuropsychiatry Clin Neurosci 12:472-9. 2000
    ..The authors conclude that assessment of behavior in long-term studies will be needed to quantify "abnormal" levels, and that item-level BRSD information could be important in clinical trials...
  14. ncbi Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease. Lu25-109 Study Group
    L J Thal
    Department of Neurosciences, University of California, San Diego School of Medicine, La Jolla 92093 0624, USA
    Neurology 54:421-6. 2000
    ..To evaluate the therapeutic effect of the selective muscarinic receptor m1 partial agonist, m2 antagonist, Lu25-109-a compound that directly stimulates muscarinic cholinergic receptors-in patients with probable AD...
  15. ncbi In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution
    D Weisman
    Department of Neurosciences, University of California, San Diego, CA, USA
    Neurology 69:356-9. 2007
    ..Clinical diagnosis of DLB, however, depended on the presence of low Alzheimer disease pathology (by Braak staging) rather than on Lewy body distribution...
  16. ncbi Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer's disease
    M W Bondi
    San Diego Veterans Affairs Medical Center and Department of Psychiatry and School of Medicine, University of California, 92161, USA
    Psychol Aging 14:295-303. 1999
    ..Results support the importance of specific episodic memory changes and possession of the ApoE-epsilon4 allele in the preclinical detection of AD...
  17. ncbi Nicotinic receptor losses in dementia with Lewy bodies: comparisons with Alzheimer's disease
    R T Rei
    Erik and Ese Banck Clinical Research Center, San Diego, CA 92130 3083, USA
    Neurobiol Aging 21:741-6. 2000
    ..These data demonstrate a different pattern of nAChR loss in AD and DLB that may, in part, explain some of the differences in the two phenotypes...
  18. ncbi Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients
    B A Pappas
    Alzheimer s Disease Research Center, University of California at San Diego, La Jolla, CA 92093 0948, USA
    Neurobiol Aging 21:11-7. 2000
    ..Hippocampal ChAT correlated significantly only with recent memory scores. These results are consistent with current animal research regarding the effect of selective cholinergic lesions on behavior...
  19. ncbi Prevalence of dementia in Chamorros on Guam: relationship to age, gender, education, and APOE
    D Galasko
    Department of Neurosciences, University of California, San Diego, CA, USA
    Neurology 68:1772-81. 2007
    ..To estimate the prevalence of dementia and its clinical subtypes among Chamorros on Guam aged 65 years or older and to examine associations with age, gender, education, and APOE genotype...
  20. ncbi Relationship between severe amyloid angiopathy, apolipoprotein E genotype, and vascular lesions in Alzheimer's disease
    J M Olichney
    Alzheimer s Disease Research Center, University of California, San Diego, La Jolla, California 92093 0948, USA
    Ann N Y Acad Sci 903:138-43. 2000
    ..We discuss the implications of this finding as advancing a pathogenic role for severe CAA in producing many of the VLs commonly found in AD cases...
  21. ncbi Neuromotor abnormalities and risk for psychosis in Alzheimer's disease
    M P Caligiuri
    Department of Psychiatry, University of California, San Diego, and the UCSD Alzheimer s Disease Research Center, La Jolla, CA 92093, USA
    Neurology 61:954-8. 2003
    ....
  22. ncbi Does apolipoprotein E (Apo-E) genotype influence nicotinic receptor binding in Alzheimer's disease
    R T Reid
    Erik and Ese Banck Clinical Research Center, San Diego, CA, USA
    J Neural Transm 108:1043-50. 2001
    ..4, and 6.0 +/- 1.0 fmol/mg protein for epsilon-/epsilon-, epsilon4/epsilon-, and epsilon4/epsilon4 respectively. We conclude that the presence or absence of the Apo-E4 genotype does not influence the loss of high affinity nAChR in AD...
  23. ncbi Early and persistent alterations in prefrontal cortex MAO A and B in Alzheimer's disease
    B P Kennedy
    Department of Medicine, University of California, San Diego Medical Center, San Diego, CA 92103, USA
    J Neural Transm 110:789-801. 2003
    ..We conclude that the changes in MAO A and B in the prefrontal cortex occur very early in Alzheimer's disease and remain relatively constant as the disease progresses...
  24. ncbi Disparate letter and semantic category fluency deficits in autopsy-confirmed frontotemporal dementia and Alzheimer's disease
    Katya Rascovsky
    Department of Neurosciences, University of California, San Diego, CA, USA
    Neuropsychology 21:20-30. 2007
    ..These unique patterns of letter and semantic category fluency deficits may be indicative of differences in the relative contribution of frontal-lobe-mediated retrieval deficits and temporal-lobe-mediated semantic deficits in FTD and AD...
  25. ncbi Neurocognitive impairment is an independent risk factor for death in HIV infection. San Diego HIV Neurobehavioral Research Center Group
    R J Ellis
    Department of Neurosciences, University of California, Department of Medicine, San Diego, USA
    Arch Neurol 54:416-24. 1997
    ..To determine if mortality is increased in individuals with human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders less severe than frank dementia...
  26. ncbi Abnormal verbal event related potentials in mild cognitive impairment and incipient Alzheimer's disease
    J M Olichney
    Department of Neurosciences, University of California, San Diego, California, USA
    J Neurol Neurosurg Psychiatry 73:377-84. 2002
    ..It has been reported that patients with amnesia have a reduced effect of word repetition upon the late positive component of the event related potential (ERP), which peaks at around 600 ms after word onset...
  27. ncbi Influence of Alzheimer pathology on clinical diagnostic accuracy in dementia with Lewy bodies
    A R Merdes
    Department of Neurosciences, University of California, San Diego 92161, USA
    Neurology 60:1586-90. 2003
    ..0039). CONCLUSIONS: The degree of concomitant AD tangle pathology has an important influence on the clinical characteristics and, therefore, the clinical diagnostic accuracy of DLB...
  28. ncbi Estrogen replacement therapy for treatment of mild to moderate Alzheimer disease: a randomized controlled trial. Alzheimer's Disease Cooperative Study
    R A Mulnard
    Institute for Brain Aging and Dementia, University of California, Irvine 92697 4540, USA
    JAMA 283:1007-15. 2000
    ..Several reports from small clinical trials have suggested that estrogen replacement therapy may be useful for the treatment of Alzheimer disease (AD) in women...
  29. ncbi Cognitive discrepancies versus APOE genotype as predictors of cognitive decline in normal-functioning elderly individuals: a longitudinal study
    Eric M Fine
    Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA
    Am J Geriatr Psychiatry 16:366-74. 2008
    ....
  30. ncbi A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment
    Leon J Thal
    University of California, San Diego, CA, USA
    Neuropsychopharmacology 30:1204-15. 2005
    ..In conjunction with the lack of effects observed in previous AD studies, the findings suggest that inhibition of COX-2 is not a useful therapeutic approach in AD...
  31. ncbi Diagnostic validity of the dementia questionnaire for Alzheimer disease
    R J Ellis
    Department of Neurosciences, University of California, San Diego, La Jolla 92093 0948, USA
    Arch Neurol 55:360-5. 1998
    ..To determine the sensitivity and specificity of postmortem dementia diagnoses based on a retrospective informant interview by comparison with criterion standard neuropathological diagnoses and the results of previous clinical examinations...
  32. ncbi Alzheimer's disease can be accurately diagnosed in very mildly impaired individuals
    D P Salmon
    Department of Neurosciences, University of California, San Diego, La Jolla, USA
    Neurology 59:1022-8. 2002
    ..Unfortunately, there is little systematically acquired information about the accuracy of the AD diagnosis in very mildly impaired patients...
  33. ncbi Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease
    R E Davis
    MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121, USA
    Proc Natl Acad Sci U S A 94:4526-31. 1997
    ..We suggest that specific point mutations in the CO1 and CO2 genes cause the CO defect in AD. A CO defect may represent a primary etiologic event, directly participating in a cascade of events that results in AD...
  34. ncbi Clinical features and changing patterns of neurodegenerative disorders on Guam, 1997-2000
    D Galasko
    Department of Neurosciences, University of California, San Diego, USA
    Neurology 58:90-7. 2002
    ..Although ALS and PDC were reported to have dramatically declined in the 1980s, new cases are still encountered. Late-life dementia has received little study among Chamorros...
  35. ncbi Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials
    Michael Grundman
    Alzheimer s Disease Cooperative Study, Department of Neurosciences, University of California San Diego, 8950 Villa La Jolla Drive, Suite 227, La Jolla, CA 92037, USA
    Arch Neurol 61:59-66. 2004
    ..The Memory Impairment Study (MIS) is a multicenter clinical trial in patients with MCI designed to evaluate whether vitamin E or donepezil is effective at delaying the time to a clinical diagnosis of AD...
  36. ncbi A comparison of episodic memory deficits in neuropathologically-confirmed Dementia with Lewy bodies and Alzheimer's disease
    Joanne M Hamilton
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093 0948, USA
    J Int Neuropsychol Soc 10:689-97. 2004
    ..These results indicate that while both DLB and AD patients exhibit significant memory impairment, the ability to consolidate information may be less severely impaired in DLB patients than in AD patients...
  37. ncbi Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment
    Adam Fleisher
    Department of Neurosciences, University of California San Diego, La Jolla, Calif, USA
    Arch Neurol 62:953-7. 2005
    ..The presence of the apolipoprotein E epsilon4 (APOE*E4) allele has been associated with greater hippocampal atrophy in women than in men with Alzheimer disease. This relationship has not been demonstrated in MCI...
  38. ncbi Growth factor gene therapy for Alzheimer disease
    Mark H Tuszynski
    Department of Neurosciences, Division of Neurosurgery, University of California at San Diego, La Jolla, California 92093, USA
    Neurosurg Focus 13:e5. 2002
    ..In this article the authors summarize the development and implementation of nerve growth factor gene delivery as a potential means of reducing cell loss in AD...
  39. ncbi Emergent psychopathology in Alzheimer's disease patients over 12 months associated with functional, not cognitive, changes
    Rochelle E Tractenberg
    Department of Neurosciences, University of California, San Diego, La Jolla 92093-0949, USA
    J Geriatr Psychiatry Neurol 15:110-7. 2002
    ....
  40. ncbi Hippocampal volume is associated with memory but not monmemory cognitive performance in patients with mild cognitive impairment
    Michael Grundman
    Department of Neurosciences, University of California, San Diego, La Jolla 92093 0949, USA
    J Mol Neurosci 20:241-8. 2003
    ..We conclude that the relationship between hippocampal volume and risk of AD is likely tied to reduced memory performance and not associated with impairment in nonmemory cognitive domains...
  41. ncbi Neuropsychological deficits associated with Alzheimer's disease in the very-old: discrepancies in raw vs. standardized scores
    Mark W Bondi
    VA San Diego Healthcare System, San Diego, California 92161, USA
    J Int Neuropsychol Soc 9:783-95. 2003
    ..These data suggest that the profile of neuropsychological deficits associated with AD in the Very-Old lacks the disproportionate saliency of episodic memory and executive function deficits typical of the Young-Old...
  42. ncbi Phase 2 safety trial targeting amyloid beta production with a gamma-secretase inhibitor in Alzheimer disease
    Adam S Fleisher
    University of California, San Diego, La Jolla, CA 92037, USA
    Arch Neurol 65:1031-8. 2008
    ..To evaluate the safety, tolerability, and amyloid beta (Abeta) response to the gamma-secretase inhibitor LY450139 in Alzheimer disease...
  43. ncbi Identification of Alzheimer disease risk by functional magnetic resonance imaging
    Adam S Fleisher
    Department of Neurosciences, University of California, San Diego, La Jolla 92037, USA
    Arch Neurol 62:1881-8. 2005
    ..Functional magnetic resonance imaging plays a promising role in the preclinical characterization of Alzheimer disease (AD) for use in early diagnosis and in preventive drug trials...
  44. ncbi Progressive impairment on neuropsychological tasks in a longitudinal study of preclinical Alzheimer's disease
    Laura Mickes
    Department of Psychology, University of California, San Diego, CA 92093 0109, USA
    Neuropsychology 21:696-705. 2007
    ....
  45. ncbi Brain MRI hippocampal volume and prediction of clinical status in a mild cognitive impairment trial
    Michael Grundman
    Department of Neurosciences, University of California, San Diego, La Jolla, USA
    J Mol Neurosci 19:23-7. 2002
    ..In summary, these data suggest that MRI hippocampal volume may be a useful correlate of disease severity in MCI subjects and a prognostic indicator of subsequent AD...
  46. ncbi APOE genotype predicts depression in women with Alzheimer's disease: a retrospective study
    Lisa Delano-Wood
    VA San Diego Healthcare System, San Diego, CA 92161, USA
    Int J Geriatr Psychiatry 23:632-6. 2008
    ..The association between the APOE epsilon4 allele and depression was investigated in a retrospective study of 323 AD patients...
  47. ncbi Age at onset is associated with disease severity in Lewy body variant and Alzheimer's disease
    Gilbert J Ho
    Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093-0624, USA
    Neuroreport 13:1825-8. 2002
    ..Taken together, these results suggest that for both LBV and AD, earlier age at onset may predict a more aggressive disease course...
  48. ncbi A phase I study of AIT-082 in healthy elderly volunteers
    Michael Grundman
    Department of Neurosciences, University of California, San Diego, La Jolla 92037, USA
    J Mol Neurosci 18:283-93. 2002
    ..In conclusion, AIT-082 was rapidly absorbed by the oral route with a half-life suitable for once daily dosing. No problems with tolerability or safety were demonstrated...
  49. ncbi High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial
    Paul S Aisen
    Department of Neurosciences, University of California, San Diego, 9500 Gilman Dr, M C 0949, La Jolla, CA 92093, USA
    JAMA 300:1774-83. 2008
    ..Prior studies of B vitamins to reduce homocysteine in AD have not had sufficient size or duration to assess their effect on cognitive decline...
  50. ncbi ADCS Prevention Instrument Project: development of a brief verbal memory test for primary prevention clinical trials
    David P Salmon
    Department of Neurosciences, University of California, San Diego, La Jolla, California 92093 0948, USA
    Alzheimer Dis Assoc Disord 20:S139-46. 2006
    ....
  51. ncbi Estimating the prevalence of agitation in community-dwelling persons with Alzheimer's disease
    Rochelle E Tractenberg
    Alzheimer s Disease Cooperative Study, Department of Neurosciences, University of California, San Diego, La Jolla 92093 0949, USA
    J Neuropsychiatry Clin Neurosci 14:11-8. 2002
    ..The authors conclude that the best estimate of prevalence of excessive agitation in this population is 67.5%, and that individuals with CMAI scores of 0 to 14 probably should not be considered to have excessive agitation...
  52. ncbi Investigating emergent symptomatology as an outcome measure in a behavioral study of Alzheimer's disease
    Rochelle E Tractenberg
    Alzheimer s Disease Cooperative Study, Department of Neurosciences, University of California, San Diego 92093 0949, USA
    J Neuropsychiatry Clin Neurosci 14:303-10. 2002
    ..The ratio of expected to observed emergence provides an intuitively appealing quantification of treatment efficacy and can be used with any instrument that uses categorical or frequency ratings...
  53. ncbi Visuospatial deficits predict rate of cognitive decline in autopsy-verified dementia with Lewy bodies
    Joanne M Hamilton
    Department of Neurosciences, University of California, USA
    Neuropsychology 22:729-37. 2008
    ....
  54. ncbi Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response
    S Duke Han
    University of California San Diego, Department of Psychiatry, La Jolla, CA 92093 0603, United States
    Neurobiol Aging 28:238-47. 2007
    ....
  55. ncbi Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord
    P J Horner
    The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA
    J Neurosci 20:2218-28. 2000
    ....
  56. ncbi A multicenter, randomized, placebo controlled, multiple-dose, safety and pharmacokinetic study of AIT-082 (Neotrofin) in mild Alzheimer's disease patients
    M Grundman
    Department of Neurosciences, University of California San Diego, 9500 Gilman, La Jolla, CA 92093, USA
    Life Sci 73:539-53. 2003
    ..No problems with tolerability or safety were found. AIT-082 appears suitable for testing in larger clinical trials for the treatment of AD and other neurologic disorders...
  57. ncbi Extrapyramidal motor signs in clinically diagnosed Alzheimer disease
    R J Ellis
    Department of Neurosciences, University of California, San Diego, USA
    Alzheimer Dis Assoc Disord 10:103-14. 1996
    ..Investigators should report frequencies for individual parkinsonian signs in addition to the overall prevalence of EPS to facilitate meaningful comparisons across studies...
  58. ncbi Altered p59Fyn kinase expression accompanies disease progression in Alzheimer's disease: implications for its functional role
    Gilbert J Ho
    Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0624, USA
    Neurobiol Aging 26:625-35. 2005
    ..Taken together, these findings suggest that alterations in Fyn localization might be associated with neurofibrillary pathology and synapse loss in AD...
  59. ncbi The role of biomarkers in clinical trials for Alzheimer disease
    Leon J Thal
    University of California San Diego, Department of Neurosciences, La Jolla, California, USA
    Alzheimer Dis Assoc Disord 20:6-15. 2006
    ..Additionally, biochemical biomarkers in blood or cerebrospinal fluid are assessed. Currently appropriate uses of biomarkers in the study of Alzheimer disease, and areas where additional work is needed, are discussed...
  60. ncbi Sensory testing in human immunodeficiency virus type 1-infected men. HIV Neurobehavioral Research Center Group
    S J Gulevich
    Department of Neurosciences, University of California, San Diego School of Medicine
    Arch Neurol 49:1281-4. 1992
    ..Subclinical peripheral neuropathy is thus related to stage of HIV infection and is present by quantitative sensory testing in 36% of patients with AIDS or ARC...
  61. ncbi Intraparenchymal nerve growth factor improves behavioral deficits while minimizing the adverse effects of intracerebroventricular delivery
    D P Pizzo
    Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
    Neuroscience 124:743-55. 2004
    ..These data suggest that intraparenchymal infusion of growth factors may provide a viable delivery method in clinical trials using this mode of drug delivery once an optimal dose has been established...
  62. ncbi Nerve growth factor promotes survival of new neurons in the adult hippocampus
    Helena Frielingsdorf
    Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0624, USA
    Neurobiol Dis 26:47-55. 2007
    ..Taken together, these findings suggest that NGF, likely mediated through increased cholinergic tone, promotes neurogenesis in the adult hippocampus, which may relate to the nootropic action of NGF...
  63. ncbi The septohippocampal cholinergic system and spatial working memory in the Morris water maze
    Helena Frielingsdorf
    Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA
    Behav Brain Res 168:37-46. 2006
    ..In conclusion, impairments in working memory as assessed by the mwm could not be revealed despite a greater than 90% loss of hippocampal ChAT and the use of optimal testing parameters and NGF treatment...
  64. ncbi Reliability of monitoring the clinical dementia rating in multicenter clinical trials
    Kimberly A Schafer
    Department of Neurosciences, University of California, San Diego, CA, USA
    Alzheimer Dis Assoc Disord 18:219-22. 2004
    ..83, global CDR) agreement. CONCLUSIONS: The ADCS-CDR worksheets were reliably and consistently scored by clinical monitors, who may be considered proxy gold standards for CDR assessment...
  65. ncbi Cognitive profiles differ in autopsy-confirmed frontotemporal dementia and AD
    K Rascovsky
    Department of Neurosciences, University of California at San Diego, La Jolla 92093 0948, USA
    Neurology 58:1801-8. 2002
    ..Therefore, a retrospective examination of neuropsychological test performance in autopsy-confirmed patients is warranted...
  66. ncbi Choline transporter 1 maintains cholinergic function in choline acetyltransferase haploinsufficiency
    Eugene P Brandon
    Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
    J Neurosci 24:5459-66. 2004
    ..Increased ChT activity may compensate for the reduced ChAT activity in Chat+/- mice, contributing to the maintenance of apparently normal cholinergic function as reflected by normal performance of these mice in several behavioral assays...
  67. ncbi Regulatable acetylcholine-producing fibroblasts enhance cognitive performance
    Donald P Pizzo
    Department of Neurosciences, University of California at San Diego, VA Medical Center MC 9151, La Jolla, CA 92093-9157, USA
    Mol Ther 13:175-82. 2006
    ....
  68. ncbi Expression pattern of synucleins (non-Abeta component of Alzheimer's disease amyloid precursor protein/alpha-synuclein) during murine brain development
    L J Hsu
    Department of Neuroscience, University of California San Diego, La Jolla 92093 0624, USA
    J Neurochem 71:338-44. 1998
    ....
  69. ncbi The Alzheimer's disease neuroimaging initiative
    Susanne G Mueller
    Department of Radiology, University of California, San Francisco, CA, USA
    Neuroimaging Clin N Am 15:869-77, xi-xii. 2005
    ..The Alzheimer's Disease Neuroimaging Initiative will help identify clinical, neuroimaging, and biomarker outcome measures that provide the highest power for measurement of longitudinal changes and for prediction of transitions...
  70. ncbi Modulation of sensory inputs and ectopic presence of Schwann cells depend upon the route and duration of nerve growth factor administration
    Donald P Pizzo
    Department of Neurosciences, University of California-San Diego, La Jolla, CA 92093-0624, USA
    Exp Neurol 178:91-103. 2002
    ..Thus, current trophic factor delivery methods require further refinement to abolish detrimental effects...
  71. ncbi Mnemonic deficits in animals depend upon the degree of cholinergic deficit and task complexity
    Donald P Pizzo
    Department of Neurosciences, University of California San Diego, La Jolla, California 92093-0624, USA
    Exp Neurol 177:292-305. 2002
    ..Our findings suggest that a dynamic interplay exists between the degree of cholinergic deficit and task demands revealing different types of mnemonic impairments...
  72. ncbi Long-term production of choline acetyltransferase in the CNS after transplantation of fibroblasts modified with a regulatable vector
    Donald P Pizzo
    Department of Neurosciences, University of California San Diego, La Jolla, CA 92023, USA
    Brain Res Mol Brain Res 126:1-13. 2004
    ..Removal of DOX led to a derepression of ChAT activity within 2 days. These cells will be useful for ex vivo gene therapy of the cholinergic system...
  73. ncbi Lesions of the nucleus basalis magnocellularis induced by 192 IgG-saporin block memory enhancement with posttraining norepinephrine in the basolateral amygdala
    Ann E Power
    Center for the Neurobiology of Learning and Memory, Department of Neurobiology and Behavior, University of California, Irvine, CA 92697 3800, USA
    Proc Natl Acad Sci U S A 99:2315-9. 2002
    ..Choline acetyltransferase assays of frontal and occipital cortices confirmed the NBM lesions. These findings indicate that cholinergic NBM-cortex projections are required for BLA-mediated modulation of memory consolidation...
  74. ncbi How to define treatment success using cholinesterase inhibitors
    Leon J Thal
    Int J Geriatr Psychiatry 17:388-90. 2002
  75. ncbi Qualitative estimates of medial temporal atrophy as a predictor of progression from mild cognitive impairment to dementia
    Charles DeCarli
    Department of Neurology and Imaging of Dementia and Aging Laboratory, Center for Neuroscience, University of California at Davis, Sacramento 95817, USA
    Arch Neurol 64:108-15. 2007
    ..Prognostic uncertainty suggests the need for additional measures to assist the clinician...
  76. ncbi Assessing Alzheimer's disease patients with the Cohen-Mansfield Agitation Inventory: scoring and clinical implications
    Myron F Weiner
    Departments of Psychiatry and Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9070, USA
    J Psychiatr Res 36:19-25. 2002
    ....
  77. ncbi Decline in verbal memory during preclinical Alzheimer's disease: examination of the effect of APOE genotype
    Kelly L Lange
    Joint Doctoral Program in Clinical Psychology, San Diego State University University of California, USA
    J Int Neuropsychol Soc 8:943-55. 2002
    ..The presence of an APOE-epsilon4 allele, however, did have a differential effect on the sensitivity of the 2 types of memory tests for tracking progression and made an independent contribution to the prediction of conversion to AD...
  78. ncbi A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer's disease
    Clifford Singer
    Department of Psychiatry, Oregon Health and Science University, Portland, USA
    Sleep 26:893-901. 2003
    ..To determine the safety and efficacy of 2 dose formulations of melatonin for the treatment of insomnia in patients with Alzheimer's disease...
  79. ncbi Early and widespread cholinergic losses differentiate dementia with Lewy bodies from Alzheimer disease
    Pietro Tiraboschi
    Neurologia, Ospedale San Paolo, Milano, Italy
    Arch Gen Psychiatry 59:946-51. 2002
    ..Conversely, in LBV, loss of ChAT activity is already prominent in the earliest stages of the illness, suggesting that cholinergic replacement therapy may be more effective in LBV than in AD, especially in mild-stage disease...
  80. ncbi No long-term effect of behavioral treatment on psychotropic drug use for agitation in Alzheimer's disease patients
    Myron F Weiner
    Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, USA
    J Geriatr Psychiatry Neurol 15:95-8. 2002
    ..0 for subjects in each drug arm or placebo arm versus BMTs. We concluded that teaching caregivers BMTs did not diminish long-term prescription of psychotropic drugs...
  81. ncbi Rofecoxib in patients with mild cognitive impairment: further analyses of data from a randomized, double-blind, trial
    Paul S Aisen
    Georgetown University Medical Center, Washington, DC, USA
    Curr Alzheimer Res 5:73-82. 2008
    ..The significance of the observation that rofecoxib increased the rate of conversion from MCI to AD remains uncertain...
  82. ncbi Evidence that common variation in NEDD9 is associated with susceptibility to late-onset Alzheimer's and Parkinson's disease
    Yonghong Li
    Celera, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA
    Hum Mol Genet 17:759-67. 2008
    ..These data implicate NEDD9 as a novel susceptibility gene for LOAD and possibly PD...
  83. ncbi ADCS Prevention Instrument Project: pharmacoeconomics: assessing health-related resource use among healthy elderly
    Mary Sano
    Mount Sinai School of Medicine, James J Peters VAMC, Bronx, NY 10468, USA
    Alzheimer Dis Assoc Disord 20:S191-202. 2006
    ..In addition, the loss that relates to the subjects' own time as they transition through cognitive impairment is not well documented...
  84. ncbi Independence of changes in behavior from cognition and function in community-dwelling persons with Alzheimer's disease: a factor analytic approach
    Rochelle E Tractenberg
    Department of Biomathematics and Biostatistics, Georgetown University School of Medicine, 7 East Main, M702, Georgetown University Hospital, 3800 Reservoir Rd, NW, Washington, DC 20007, USA
    J Neuropsychiatry Clin Neurosci 17:51-60. 2005
    ..Cognitive and functional subscores for the CDR were supported. These findings suggest that changes in behavior and cognition in dementia may have distinct pathophysiologies...
  85. ncbi Executive dysfunction in Alzheimer disease
    Margaret M Swanberg
    Department of Neurology, David Geffen School of Medicine at UCLA, 90095-1769, USA
    Arch Neurol 61:556-60. 2004
    ..CONCLUSION: These findings support the assessment of executive function in persons with AD and the importance of frontal lobe dysfunction in AD...
  86. ncbi Vitamin E and donepezil for the treatment of mild cognitive impairment
    Ronald C Petersen
    Mayo Clinic College of Medicine, Rochester, Minn, USA
    N Engl J Med 352:2379-88. 2005
    ....
  87. ncbi Regression to the mean: implications for clinical trials of psychotropic agents in dementia
    Jeffrey L Cummings
    Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095 1769, USA
    Curr Alzheimer Res 1:323-8. 2004
    ..Research design adjustments such as collection of both screening and baseline measures to determine eligibility may limit the effects of regression to the mean on trial outcomes and reduce this challenge to clinical trials...
  88. ncbi What best differentiates Lewy body from Alzheimer's disease in early-stage dementia?
    Pietro Tiraboschi
    Dipartimento di Scienze Neurologiche, Ospedale Niguarda Ca Granda, Milano, Italy
    Brain 129:729-35. 2006
    ..This suggests that clinical history plus a brief assessment of visuospatial function may be of the greatest value in correctly identifying DLB early during the course of disease...
  89. ncbi Comorbidity of psychopathological domains in community-dwelling persons with Alzheimer's disease
    Rochelle E Tractenberg
    Center for Population and Health, Georgetown University, Washington, DC 20057 1197, USA
    J Geriatr Psychiatry Neurol 16:94-9. 2003
    ..Significant psychopathological comorbidity should be considered in the design of clinical trials targeting particular psychopathology in this disease population...
  90. ncbi Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial
    Paul S Aisen
    Department of Neurology, Georgetown University Medical Center, Washington, DC 20057, USA
    JAMA 289:2819-26. 2003
    ....
  91. ncbi DAPK1 variants are associated with Alzheimer's disease and allele-specific expression
    Yonghong Li
    Celera Diagnostics, Alameda, CA 94502, USA
    Hum Mol Genet 15:2560-8. 2006
    ..015 to <0.0001). These data suggest that genetic variation in DAPK1 modulates susceptibility to LOAD...
  92. ncbi NSAIDs and hypertension
    Paul S Aisen
    Arch Intern Med 163:1115; author reply 1115-6. 2003
  93. ncbi Spanish instrument protocol: new treatment efficacy instruments for Spanish-speaking patients in Alzheimer disease clinical trials
    Mary Sano
    Mount Sinai School of Medicine, Bronx, NY, USA
    Alzheimer Dis Assoc Disord 20:232-41. 2006
    ....
  94. ncbi ADCS Prevention Instrument Project: overview and initial results
    Steven H Ferris
    Alzheimer s Disease Center, New York University School of Medicine, New York, NY 10016, USA
    Alzheimer Dis Assoc Disord 20:S109-23. 2006
    ..Initial results for the experimental instruments and for the book club are reported in separate accompanying articles...
  95. ncbi Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI
    Clifford R Jack
    Department of Radiology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
    Neurobiol Aging 29:1285-95. 2008
    ..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...
  96. ncbi The Sleep Disorders Inventory: an instrument for studies of sleep disturbance in persons with Alzheimer's disease
    Rochelle E Tractenberg
    Department of Biomathematics and Biostatistics, Georgetown University School of Medicine, Washington, DC 20057, USA
    J Sleep Res 12:331-7. 2003
    ..The SDI covers a wide range of sleep behaviors and provides information independent of sleep time and SQR...
  97. ncbi Toward optimal health: Leon J. Thal, M.D. discusses the latest in Alzheimer's disease in women. Interview by Jodi R. Godfrey
    Leon J Thal
    J Womens Health (Larchmt) 15:704-8. 2006
  98. ncbi A quarter century of advancing treatment for Alzheimer's disease with Leon J. Thal
    Michael Grundman
    Alzheimer's Disease Clinical Development Program, Elan Pharmaceuticals, Inc, San Francisco, CA, USA
    Alzheimers Dement 4:S51-5. 2008

Research Grants6

  1. GENE THERAPY OF BASAL FOREBRAIN CHOLINERGIC LESIONS
    Leon Thal; Fiscal Year: 2004
    ..These approaches will not only be applicable for AD, but other neurodegenerative disorders and for delivering other transgenes of interest. ..
  2. Alzheimer's Disease Research Center Conference
    Leon Thal; Fiscal Year: 2006
    ..Partial support is requested to defray travel costs of invited speakers and to provide travel awards to minority healthcare providers, junior faculty, postdocs and students. ..