Research evaluation and diagnosis of probable  Alzheimer’s disease over the last two decades: I

López, Oscar L.; Becker, James T.; Klunk, William E.; Saxton, Judy A.; Hamilton, Ronald L.; Kaufer, Daniel I.; Sweet, Robert A.; Meltzer, Carolyn C.; Wisniewski, Stephen R.; Kamboh, M. Ilyas; DeKosky, Steven T.

doi:10.1212/wnl.55.12.1854

Cited by 150 publications

(128 citation statements)

References 52 publications

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“…All subjects were evaluated with standard neurological, psychiatric, and neuropsychological examinations through the University of Pittsburgh Alzheimer Disease Research Center (ADRC) as described previously (Lopez et al, 2000;Price et al, 2005), or with an equivalent evaluation at MGH (CY4 and CY5). The neuropsychological test battery is described below.…”

Section: Human Subjectsmentioning

confidence: 99%

Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees

Klunk¹,

Price²,

Mathis³

et al. 2007

Journal of Neuroscience

372

333

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The amyloid cascade hypothesis suggests that the aggregation and deposition of amyloid-␤ protein is an initiating event in Alzheimer's disease (AD). Using amyloid imaging technology, such as the positron emission tomography (PET) agent Pittsburgh compound-B (PiB), it is possible to explore the natural history of preclinical amyloid deposition in people at high risk for AD. With this goal in mind, asymptomatic (n ϭ 5) and symptomatic (n ϭ 5) carriers of presenilin-1 (PS1) mutations (C410Y or A426P) that lead to early-onset AD and noncarrier controls from both kindreds (n ϭ 2) were studied with PiB-PET imaging and compared with sporadic AD subjects (n ϭ 12) and controls from the general population (n ϭ 18). We found intense and focal PiB retention in the striatum of all 10 PS1 mutation carriers studied (ages 35-49 years). In most PS1 mutation carriers, there also were increases in PiB retention compared with controls in cortical brain areas, but these increases were not as great as those observed in sporadic AD subjects. The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not show the typical regional pattern of PiB retention observed in sporadic AD. Postmortem evaluation of tissue from two parents of PS1C410Y subjects in this study confirmed extensive striatal amyloid deposition, along with typical cortical deposition. The early, focal striatal amyloid deposition observed in these PS1 mutation carriers is often is not associated with clinical symptoms.

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Section: Human Subjectsmentioning

confidence: 99%

Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees

Klunk¹,

Price²,

Mathis³

et al. 2007

Journal of Neuroscience

372

333

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“…All participants were recruited and evaluated through the University of Pittsburgh Alzheimer Disease Research Center (ADRC) and underwent detailed neurobehavioral evaluations before being given consensus diagnosis by neurologists, neuropsychiatrists, psychiatrists, and a neuroradiologist. The AD subjects met NINDS-ADRDA criteria for Probable AD (McKhann et al, 1984) and MCI subjects were classified using previously reported criteria (Lopez et al 2000). Each subject had a Mini Mental State Exam (MMSE) administered within one day of the PiB scan.…”

Section: Subjectsmentioning

confidence: 99%

Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer's disease with Pittsburgh Compound B

Raji

Becker

Tsopelas

et al. 2008

Journal of Neuroscience Methods

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We evaluated the region-to-region correlation, laterality and asymmetry of amyloid deposition in subjects with mild cognitive impairment (MCI) or Alzheimer's Disease (AD) using the amyloid tracer, Pittsburgh-Compound B (PiB). Seventeen subjects, including 7 with MCI (MMSE 26.7 ± 2.4) and 10 with AD (MMSE of 24.8 ± 2.7) underwent PiB imaging. Measures of laterality (i.e. groupwise predilection for right or left) and asymmetry (i.e. group-wise predilection for unequal PiB retention between the two hemispheres) were calculated for seventeen Regions of Interest (ROIs). Regional correlations were calculated along with within-group and between-groups statistical analyses of laterality and asymmetry metrics. The median correlation between PiB retention across all pairs of ROIs was 0.65, with highest correlations found in areas of highest PiB retention, (r = 0.74). Overall, PiB retention was symmetric bilaterally, but there was PiB laterality in MCI in dorsal frontal cortex [(t(6) = 3.05, p = 0.02, L>R] and sensory-motor area [t(6) = 3.10, p = 0.02, L>R] and in AD in the occipital pole (t(9) = −2.63, p = 0.03, R>L). The most significant asymmetries in PiB retention were found in sub-cortical white matter (t(6) = 3.99, p = 0.01) and middle precuneus [(t(6)

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“…Subjects underwent an extensive diagnostic and behavioral assessment, which has been described in detail elsewhere, 6,[25][26][27][28] and received a diagnosis of possible or probable AD utilizing the National Institute of Neurologic and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association criteria. 29 The rate of autopsy confirmation of AD in subjects diagnosed with possible and probable AD exceeds 90% in our center.…”

Section: Subjectsmentioning

confidence: 99%

“…29 The rate of autopsy confirmation of AD in subjects diagnosed with possible and probable AD exceeds 90% in our center. 25,26 Assessment of psychosis was performed using the Empirical Behavioral Pathology in Alzheimer Disease scale (E-BEHAVE-AD) 30 for patients from the Geriatric Psychiatry Inpatient Program, and the Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer Disease for subjects at the ADRC. 31 Psychosis was defined by the presence of persistent hallucinations or delusions occurring at any time during the course of the dementia.…”

Section: Subjectsmentioning

confidence: 99%

Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease

Devlin

et al. 2005

Mol Psychiatry

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Psychotic symptoms in subjects with Alzheimer disease (AD with psychosis, AD þ P) define a phenotype characterized by greater cognitive burden than in AD without psychosis. We have proposed that genes of small effect may contribute to the risk for expression of psychosis in multiple disorders, including AD. Recently, sex-differential association of a three-locus haplotype, including a G-A transition at codon 108/158 of catechol-O-methyltransferase (COMT) resulting in a Val-Met substitution, has been reported to confer an increased risk for schizophrenia. The main objective of the study was to determine if COMT genetic variation is associated with risk of psychosis in AD, and included a case-control study of 373 individuals diagnosed with AD with, or without, psychosis. All subjects were characterized for alleles at the three loci associated with schizophrenia, RS737865, COMT G-A 108/158 (RS4680), and RS165599, and for a C/T transition adjacent to an estrogen response element (ERE6) in the COMT P2 promoter region. Both single locus and haplotype tests of association were conducted. Logit models were used to examine independent and interacting effects of alleles at the associated loci. All analyses were stratified by sex. In female subjects, RS4680 demonstrated a modest association with AD þ P; RS737865 demonstrated a trend towards an association. There was a highly significant association of AD þ P with the four-locus haplotype, which resulted from additive effects of alleles at RS4680 and ERE6 (or RS737865, as this locus was in almost absolute linkage disequilibrium (LD) with ERE6). In male subjects, no single locus test was significant, but there remained a strong association between AD þ P and the four-locus haplotype. This association appeared to result from interaction of the ERE6/ RS737865, RS4680, and RS165599 loci. Genetic variation in COMT is associated with AD þ P, and thus appears to contribute to psychosis risk across disorders. Sex-differential associations of COMT with psychosis may result from variation at, or in LD with, ERE6. Examination of variation at ERE6 in subjects with schizophrenia, and further examination of the independent and additive effects of variations in COMT on gene expression, is warranted.

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Research evaluation and diagnosis of probable Alzheimer’s disease over the last two decades: I

Cited by 150 publications

References 52 publications

Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees

Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees

Characterizing regional correlation, laterality and symmetry of amyloid deposition in mild cognitive impairment and Alzheimer's disease with Pittsburgh Compound B

Catechol-O-methyltransferase haplotypes are associated with psychosis in Alzheimer disease

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