Claudia Muñoz - Academia.edu (original) (raw)
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Papers by Claudia Muñoz
Alzheimer's & Dementia, 2015
VFT Normal 11 10 0.031* 6 15 0.151 12 9 0.070 Mildly impaired 5 11 2 14 7 9 Moderately impaired 4... more VFT Normal 11 10 0.031* 6 15 0.151 12 9 0.070 Mildly impaired 5 11 2 14 7 9 Moderately impaired 4 21 2 23 6 19 mBNT Normal 14 16 0.063 8 22 0.058 15 15 0.323 Mildly impaired 3 13 2 14 5 11 Moderately impaired 3 13 0 16 5 11 MMSEKC Normal 1 2 0.056 0 3 0.002* 3 0 0.014* Mildly impaired 6 3 5 4 6 3 Moderately impaired 13 37 5 45 16 34 WLMT Normal 9 11 0.088 6 14 0.103 10 10 0.451 Mildly impaired 6 8 2 14 6 8 Moderately impaired 5 23 2 26 9 19 CPT Normal 15 25 0.111 9 31 0.167 19 21 0.295 Mildly impaired 5 9 1 13 4 10 Moderately impaired 0 8 0 8 2 6 WLRT Normal 7 2 0.005* 4 5 0.042* 6 3 0.215 Mildly impaired 2 10 1 11 4 8 Moderately impaired 11 30 5 36 15 26 WLRcT Normal 11 9 0.021* 7 13 0.014* 10 10 0.301 Mildly impaired 4 9 0 13 3 10 Moderately impaired 5 24 3 26 12 17 CRT Normal 6 4 0.116 4 6 0.051 6 4 0.333 Mildly impaired 2 7 2 7 4 5 Moderately impaired 12 31 4 39 15 28
Revista Colombiana de Psiquiatría, 2014
Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto r e v c ... more Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto r e v c o l o m b p s i q u i a t. 2 0 1 4;4 3(2):113-122
The Journal of Clinical Psychiatry, 2014
Background: There is growing interest in identifying sensitive composite cognitive tests to serve... more Background: There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer's disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial. Methods: This study used a longitudinal approach to maximize sensitivity to tracking progressive cognitive decline in people who progressed to the clinical stages of AD (n = 868) compared to those who remained cognitively unimpaired during the same time period (n = 989), thereby correcting for normal aging and practice effects. Specifically, we developed the Alzheimer's Prevention Initiative Preclinical Composite Cognitive test (APCC) to measure very early longitudinal cognitive decline in older adults with preclinical AD. Data from three cohorts from Rush University were analyzed using a partial least squares (PLS) regression model to identify optimal composites within different time periods prior to diagnosis, up to 11 years prior to diagnosis. The mean-to-standard deviation ratio (MSDRs) is an indicator of sensitivity to change and was used to inform the final calculation of the composite score. Results: The optimal composite, the APCC, is calculated: 0.26*Symbol Digit Modalities + 2.24*MMSE Orientation to Time + 2.14*MMSE Orientation to Place + 0.53*Logical Memory Delayed Recall + 1.36* Word List-Delayed Recall + 0.68*Judgment of Line Orientation + 1.39*Raven's Progressive Matrices Matrices (subset of 9 items from A and B). The MSDR of the APCC in a population of preclinical AD individuals who eventually progress to cognitive impairment, compared to those who remained cognitively unimpaired during the same time period, was − 1.10 over 1 year. Conclusions: The APCC is an empirically derived composite cognitive test score with high face validity that is sensitive to preclinical AD decline up to 11 years prior to diagnosis of the clinical stages of AD. The components of the APCC are supported by theoretical understanding of cognitive decline that occurs during preclinical AD. The APCC was used as a primary outcome in the API Generation Program trials.
Alzheimer's & Dementia, 2015
Neurology, Jan 13, 2015
We identified several families in Antioquia, Colombia, with early-onset Alzheimer disease (AD) du... more We identified several families in Antioquia, Colombia, with early-onset Alzheimer disease (AD) due to the mendelian autosomal dominant inheritance of a PSEN1 E280A gene mutation. Extended family members were interviewed and parish baptism certificates in Antioquian municipalities examined. The size of these extended families (including carriers and noncarriers) approaches 5,000 individuals. Full genomes in carriers proved a single founder. 2 To support an AD prevention clinical trial, we established a registry in 2010 of all family members over age 8 years. 3 Since then we genotyped 3,407 family members and identified 823 (24%) carriers of the PSEN1 E280A mutation. The Comite de Bioetica de la Sede de Investigacion Universitaria, SIU Universidad de Antioquia, approved this study. All participants provided written informed consent. Despite the size of this exceptionally large family and frequent consanguinity, homozygosity at this gene locus had not been reported. The apparent absence of homozygous PSEN1 mutations led to the speculation that E280A homozygosity could be lethal. Generally, homozygous dominant mutations are more severely affected than heterozygotes in both humans and model systems. 4 However, human cases in which dominant point mutations are homozygous are rare.
Alzheimer's & Dementia, 2015
VFT Normal 11 10 0.031* 6 15 0.151 12 9 0.070 Mildly impaired 5 11 2 14 7 9 Moderately impaired 4... more VFT Normal 11 10 0.031* 6 15 0.151 12 9 0.070 Mildly impaired 5 11 2 14 7 9 Moderately impaired 4 21 2 23 6 19 mBNT Normal 14 16 0.063 8 22 0.058 15 15 0.323 Mildly impaired 3 13 2 14 5 11 Moderately impaired 3 13 0 16 5 11 MMSEKC Normal 1 2 0.056 0 3 0.002* 3 0 0.014* Mildly impaired 6 3 5 4 6 3 Moderately impaired 13 37 5 45 16 34 WLMT Normal 9 11 0.088 6 14 0.103 10 10 0.451 Mildly impaired 6 8 2 14 6 8 Moderately impaired 5 23 2 26 9 19 CPT Normal 15 25 0.111 9 31 0.167 19 21 0.295 Mildly impaired 5 9 1 13 4 10 Moderately impaired 0 8 0 8 2 6 WLRT Normal 7 2 0.005* 4 5 0.042* 6 3 0.215 Mildly impaired 2 10 1 11 4 8 Moderately impaired 11 30 5 36 15 26 WLRcT Normal 11 9 0.021* 7 13 0.014* 10 10 0.301 Mildly impaired 4 9 0 13 3 10 Moderately impaired 5 24 3 26 12 17 CRT Normal 6 4 0.116 4 6 0.051 6 4 0.333 Mildly impaired 2 7 2 7 4 5 Moderately impaired 12 31 4 39 15 28
Revista Colombiana de Psiquiatría, 2014
Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto r e v c ... more Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto r e v c o l o m b p s i q u i a t. 2 0 1 4;4 3(2):113-122
The Journal of Clinical Psychiatry, 2014
Background: There is growing interest in identifying sensitive composite cognitive tests to serve... more Background: There is growing interest in identifying sensitive composite cognitive tests to serve as primary endpoints in preclinical Alzheimer's disease (AD) treatment trials. We reported previously a composite cognitive test score sensitive to tracking preclinical AD decline up to 5 years prior to clinical diagnosis. Here we expand upon and refine this work, empirically deriving a composite cognitive test score sensitive to tracking preclinical AD decline up to 11 years prior to diagnosis and suitable for use as a primary endpoint in a preclinical AD trial. Methods: This study used a longitudinal approach to maximize sensitivity to tracking progressive cognitive decline in people who progressed to the clinical stages of AD (n = 868) compared to those who remained cognitively unimpaired during the same time period (n = 989), thereby correcting for normal aging and practice effects. Specifically, we developed the Alzheimer's Prevention Initiative Preclinical Composite Cognitive test (APCC) to measure very early longitudinal cognitive decline in older adults with preclinical AD. Data from three cohorts from Rush University were analyzed using a partial least squares (PLS) regression model to identify optimal composites within different time periods prior to diagnosis, up to 11 years prior to diagnosis. The mean-to-standard deviation ratio (MSDRs) is an indicator of sensitivity to change and was used to inform the final calculation of the composite score. Results: The optimal composite, the APCC, is calculated: 0.26*Symbol Digit Modalities + 2.24*MMSE Orientation to Time + 2.14*MMSE Orientation to Place + 0.53*Logical Memory Delayed Recall + 1.36* Word List-Delayed Recall + 0.68*Judgment of Line Orientation + 1.39*Raven's Progressive Matrices Matrices (subset of 9 items from A and B). The MSDR of the APCC in a population of preclinical AD individuals who eventually progress to cognitive impairment, compared to those who remained cognitively unimpaired during the same time period, was − 1.10 over 1 year. Conclusions: The APCC is an empirically derived composite cognitive test score with high face validity that is sensitive to preclinical AD decline up to 11 years prior to diagnosis of the clinical stages of AD. The components of the APCC are supported by theoretical understanding of cognitive decline that occurs during preclinical AD. The APCC was used as a primary outcome in the API Generation Program trials.
Alzheimer's & Dementia, 2015
Neurology, Jan 13, 2015
We identified several families in Antioquia, Colombia, with early-onset Alzheimer disease (AD) du... more We identified several families in Antioquia, Colombia, with early-onset Alzheimer disease (AD) due to the mendelian autosomal dominant inheritance of a PSEN1 E280A gene mutation. Extended family members were interviewed and parish baptism certificates in Antioquian municipalities examined. The size of these extended families (including carriers and noncarriers) approaches 5,000 individuals. Full genomes in carriers proved a single founder. 2 To support an AD prevention clinical trial, we established a registry in 2010 of all family members over age 8 years. 3 Since then we genotyped 3,407 family members and identified 823 (24%) carriers of the PSEN1 E280A mutation. The Comite de Bioetica de la Sede de Investigacion Universitaria, SIU Universidad de Antioquia, approved this study. All participants provided written informed consent. Despite the size of this exceptionally large family and frequent consanguinity, homozygosity at this gene locus had not been reported. The apparent absence of homozygous PSEN1 mutations led to the speculation that E280A homozygosity could be lethal. Generally, homozygous dominant mutations are more severely affected than heterozygotes in both humans and model systems. 4 However, human cases in which dominant point mutations are homozygous are rare.