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Insensitivity of visual assessment of hippocampal atrophy in familial Alzheimer's disease.

Ringman JM, Pope W, Salamon N - J. Neurol. (2010)

Bottom Line: A limitation of studies of magnetic resonance imaging (MRI) measures in AD is diagnostic uncertainty as it can be unknown if pre- or early-symptomatic subjects go on to develop AD and most subjects do not undergo autopsy verification of the diagnosis.Of the 39 subjects, 26 were FAD mutation carriers.Our results suggest that radiologists' ability to detect HA in persons in whom the diagnosis of incipient AD is certain is sub-optimal and quantitative MRI techniques or other biological markers of the disease are needed.

View Article: PubMed Central - PubMed

Affiliation: UCLA Department of Neurology, Mary S Easton Center for Alzheimer's Disease Research, UCLA, 10911 Weyburn Ave, #200 Los Angeles, CA 90095-7226, USA. jringman@mednet.ucla.edu

ABSTRACT
Medial temporal atrophy is a well-established marker for Alzheimer's disease (AD). However, due to normal variation in the size of medial temporal structures and variability in how radiologists interpret images, the use of clinical reads in establishing the presence of pathological atrophy is imprecise. A limitation of studies of magnetic resonance imaging (MRI) measures in AD is diagnostic uncertainty as it can be unknown if pre- or early-symptomatic subjects go on to develop AD and most subjects do not undergo autopsy verification of the diagnosis. In persons with or at-risk for AD due to fully-penetrant autosomal dominant mutations in the PSEN1 and APP genes, the diagnosis or future development of AD can be predicted with essentially 100% accuracy. We used this predictability to assess the ability of radiologists to detect hippocampal atrophy (HA) in persons destined to develop AD. Coronal T1-weighted MRI scans of 39 persons demented from (n = 4) or at-risk for inheriting (n = 35) PSEN1 or APP mutations were independently assessed by two radiologists and the presence or absence of HA determined. Of the 39 subjects, 26 were FAD mutation carriers. Fifteen of 28 asymptomatic at-risk persons were FAD mutation carriers and four of these were rated as having atrophy for a sensitivity of 27% and a specificity of 85%. Among seven mildly affected yet non-demented subjects, atrophy was detected in three and in the four demented subjects HA was identified in two. Our results suggest that radiologists' ability to detect HA in persons in whom the diagnosis of incipient AD is certain is sub-optimal and quantitative MRI techniques or other biological markers of the disease are needed.

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a Coronal MP-RAGE MRI of a moderately demented subject (CDR = 2) with FAD whose hippocampi were rated as having no atrophy by two experienced radiologists. b MRI of a non-mutation carrying person (age between 30 and 40 years) whose hippocampi were rated as mildly atrophic by both radiologists
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Fig1: a Coronal MP-RAGE MRI of a moderately demented subject (CDR = 2) with FAD whose hippocampi were rated as having no atrophy by two experienced radiologists. b MRI of a non-mutation carrying person (age between 30 and 40 years) whose hippocampi were rated as mildly atrophic by both radiologists

Mentions: Of the four demented subjects, two were rated as having no hippocampal atrophy (CDR scores of 2, see Fig. 1a). One subject with a CDR score of 3 was rated as having severe hippocampal atrophy bilaterally and one with a CDR score of 1 was rated as having mild hippocampal atrophy on the left side but not the right. Of the seven FAD mutation carriers with CDR scores of 0.5, four were rated as having no atrophy, one as having bilateral hippocampal atrophy, and one each with right and left hippocampal atrophy only (all mild). Of the 15 asymptomatic FAD mutation carriers, 11 were rated as having no atrophy, three had bilateral, and one had unilateral atrophy (all mild). Among the 13 non-carriers, one was rated as having bilateral (Fig. 1b) and one unilateral mild hippocampal atrophy. Of note, these two subjects were not among the oldest subjects in the cohort being between 30 and 40 years of age (specific ages not given to protect confidentiality). In this study therefore, the sensitivity and specificity of hippocampal atrophy for predicting FAD mutation status in asymptomatic subjects was 27 and 85%, respectively. Among mildly affected subjects (CDR scores of 0.5) sensitivity was 43% and in demented subjects it was 50%.Fig. 1


Insensitivity of visual assessment of hippocampal atrophy in familial Alzheimer's disease.

Ringman JM, Pope W, Salamon N - J. Neurol. (2010)

a Coronal MP-RAGE MRI of a moderately demented subject (CDR = 2) with FAD whose hippocampi were rated as having no atrophy by two experienced radiologists. b MRI of a non-mutation carrying person (age between 30 and 40 years) whose hippocampi were rated as mildly atrophic by both radiologists
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864895&req=5

Fig1: a Coronal MP-RAGE MRI of a moderately demented subject (CDR = 2) with FAD whose hippocampi were rated as having no atrophy by two experienced radiologists. b MRI of a non-mutation carrying person (age between 30 and 40 years) whose hippocampi were rated as mildly atrophic by both radiologists
Mentions: Of the four demented subjects, two were rated as having no hippocampal atrophy (CDR scores of 2, see Fig. 1a). One subject with a CDR score of 3 was rated as having severe hippocampal atrophy bilaterally and one with a CDR score of 1 was rated as having mild hippocampal atrophy on the left side but not the right. Of the seven FAD mutation carriers with CDR scores of 0.5, four were rated as having no atrophy, one as having bilateral hippocampal atrophy, and one each with right and left hippocampal atrophy only (all mild). Of the 15 asymptomatic FAD mutation carriers, 11 were rated as having no atrophy, three had bilateral, and one had unilateral atrophy (all mild). Among the 13 non-carriers, one was rated as having bilateral (Fig. 1b) and one unilateral mild hippocampal atrophy. Of note, these two subjects were not among the oldest subjects in the cohort being between 30 and 40 years of age (specific ages not given to protect confidentiality). In this study therefore, the sensitivity and specificity of hippocampal atrophy for predicting FAD mutation status in asymptomatic subjects was 27 and 85%, respectively. Among mildly affected subjects (CDR scores of 0.5) sensitivity was 43% and in demented subjects it was 50%.Fig. 1

Bottom Line: A limitation of studies of magnetic resonance imaging (MRI) measures in AD is diagnostic uncertainty as it can be unknown if pre- or early-symptomatic subjects go on to develop AD and most subjects do not undergo autopsy verification of the diagnosis.Of the 39 subjects, 26 were FAD mutation carriers.Our results suggest that radiologists' ability to detect HA in persons in whom the diagnosis of incipient AD is certain is sub-optimal and quantitative MRI techniques or other biological markers of the disease are needed.

View Article: PubMed Central - PubMed

Affiliation: UCLA Department of Neurology, Mary S Easton Center for Alzheimer's Disease Research, UCLA, 10911 Weyburn Ave, #200 Los Angeles, CA 90095-7226, USA. jringman@mednet.ucla.edu

ABSTRACT
Medial temporal atrophy is a well-established marker for Alzheimer's disease (AD). However, due to normal variation in the size of medial temporal structures and variability in how radiologists interpret images, the use of clinical reads in establishing the presence of pathological atrophy is imprecise. A limitation of studies of magnetic resonance imaging (MRI) measures in AD is diagnostic uncertainty as it can be unknown if pre- or early-symptomatic subjects go on to develop AD and most subjects do not undergo autopsy verification of the diagnosis. In persons with or at-risk for AD due to fully-penetrant autosomal dominant mutations in the PSEN1 and APP genes, the diagnosis or future development of AD can be predicted with essentially 100% accuracy. We used this predictability to assess the ability of radiologists to detect hippocampal atrophy (HA) in persons destined to develop AD. Coronal T1-weighted MRI scans of 39 persons demented from (n = 4) or at-risk for inheriting (n = 35) PSEN1 or APP mutations were independently assessed by two radiologists and the presence or absence of HA determined. Of the 39 subjects, 26 were FAD mutation carriers. Fifteen of 28 asymptomatic at-risk persons were FAD mutation carriers and four of these were rated as having atrophy for a sensitivity of 27% and a specificity of 85%. Among seven mildly affected yet non-demented subjects, atrophy was detected in three and in the four demented subjects HA was identified in two. Our results suggest that radiologists' ability to detect HA in persons in whom the diagnosis of incipient AD is certain is sub-optimal and quantitative MRI techniques or other biological markers of the disease are needed.

Show MeSH
Related in: MedlinePlus