Biomedical subjects

J H Kramer

Publications and source records attributed to J H Kramer.

At least 19 recordsLinked to original sources

PubMed2007

Diffusion tensor imaging of cingulum fibers in mild cognitive impairment and Alzheimer disease.

BACKGROUND: Neuroimaging in mild cognitive impairment (MCI) and Alzheimer disease (AD) generally shows medial temporal lobe atrophy and diminished glucose metabolism and cerebral blood flow in the posterior cingulate gyrus. However, it is unclear whether these abnormalities also impact the cingulum fibers, which connect the medial temporal lobe and the posterior cingulate regions. OBJECTIVE: To use diffusion tensor imaging (DTI), by measuring fractional anisotropy (FA), to test 1) if MCI and AD are associated with DTI abnormalities in the parahippocampal and posterior cingulate regions of the cingulum fibers; 2) if white matter abnormalities extend to the neocortical fiber connections in the corpus callosum (CC); 3) if DTI improves accuracy to separate AD and MCI from healthy aging vs structural MRI. METHODS: DTI and structural MRI were preformed on 17 patients with AD, 17 with MCI, and 18 cognitively normal (CN) subjects. RESULTS: FA of the cingulum fibers was significantly reduced in MCI, and even more in AD. FA was also significantly reduced in the splenium of the CC in AD, but not in MCI. Adding DTI to hippocampal volume significantly improved the accuracy to separate MCI and AD from CN. CONCLUSION: Assessment of the cingulum fibers using diffusion tensor imaging may aid early diagnosis of Alzheimer disease.

Aged↗

PubMed2006

Hypoperfusion in frontotemporal dementia and Alzheimer disease by arterial spin labeling MRI.

OBJECTIVES: To test if arterial spin labeling (ASL) MRI could detect a pattern of hypoperfusion in frontotemporal dementia (FTD) vs cognitively normal (CN) control subjects; to determine the regional difference of perfusion between FTD and Alzheimer disease (AD); and to determine whether hypoperfusion in FTD correlates with cognitive impairment. METHODS: We included 21 patients with FTD, 24 patients with AD, and 25 CN subjects in this cross-sectional MRI study. All subjects had MRI scans including T1-weighted structural images and ASL-MR images. RESULTS: ASL-MRI detected a pattern of hypoperfusion in right frontal regions in patients with FTD vs CN subjects, similar to PET and SPECT. FTD had higher perfusion than AD in the parietal regions and posterior cingulate. Frontal hypoperfusion in FTD correlated with deficits in judgment and problem solving. Adding frontal perfusion to gray matter (GM) atrophy significantly improved the classification of FTD from normal aging to 74%, and adding parietal perfusion to GM atrophy significantly improved the classification of FTD from AD to 75%. Combining frontal and parietal lobe perfusion further improved the classification of FTD from AD to 87%. CONCLUSION: Frontotemporal dementia and Alzheimer disease display different spatial distributions of hypoperfusion on arterial spin labeling MRI. With further development and evaluation, arterial spin labeling MRI could contribute to the differential diagnosis between frontotemporal dementia and Alzheimer disease.

Adult↗

PubMed2006

Andersen-Tawil syndrome: definition of a neurocognitive phenotype.

BACKGROUND: The Andersen-Tawil syndrome (ATS) is a potassium ion channelopathy caused by mutations in the KCNJ2 gene. It is characterized by periodic paralysis, cardiac arrhythmias, and distinctive features; the effect of KCNJ2 mutations on the CNS has never been studied. OBJECTIVE: To define a potential CNS phenotype in ATS using standardized methods. METHODS: Ten subjects with KCNJ2 mutations and their unaffected siblings were evaluated at the University of California San Francisco General Clinical Research Center. A comprehensive battery of neurocognitive tests was administered to ATS subjects and their unaffected siblings, followed by pairwise analysis of the resultant differences in scores. An EEG was obtained for all ATS subjects. RESULTS: There was no EEG evidence of subclinical seizure activity in any subject. ATS subjects universally had more school difficulties than their siblings, despite similar IQ between the two groups. On formal neurocognitive testing, there was no difference between ATS subjects and their siblings on tests of verbal and visual memory. Assessment of executive functioning revealed ATS subjects scored 1.93 points lower than their siblings on tests of Design Fluency (95% CI -3.46, 0.01; p = 0.052) and made 1.9 more errors (95% CI 0.46, 2.54; p = 0.005). Subjects with ATS scored an average of 5 points lower than their siblings on tests of matrix reasoning (95% CI -8.67, -1.33; p = 0.008). On tests of general ability, ATS subjects achieved much lower scores than their siblings, with an average difference of 9.13 points for reading (95% CI -12.46, 3.21; p = 0.056) and 23.4 points for mathematics (95% CI -42.53, -4.22; p = 0.017). CONCLUSION: Mutations in KCNJ2 are associated with a distinct neurocognitive phenotype, characterized by deficits in executive function and abstract reasoning.

Adolescent↗

PubMed2006

Andersen-Tawil syndrome: prospective cohort analysis and expansion of the phenotype.

Andersen-Tawil syndrome (ATS) is an autosomal dominant multisystem disorder characterized by developmental, cardiac, and neuromuscular abnormalities. Approximately 70% of patients have mutations in KCNJ2, resulting in dysfunction of the inward-rectifying potassium channel Kir2.1. Variable expression complicates the diagnosis of ATS, which in many cases, is not made until years after the first recognized symptom. To better define the distinctive clinical features of ATS and facilitate earlier diagnosis, we conducted a prospective, standardized evaluation of 10 subjects with confirmed KCNJ2 mutations. Detailed anthropometric, neurological, and cardiac evaluations were performed. Using this approach, we identified novel skeletal and dental findings and proposed additional diagnostic criteria for ATS dysmorphology.

Abnormalities, Multiple↗

PubMed2005

Frontotemporal dementia progresses to death faster than Alzheimer disease.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is a common cause of non-Alzheimer dementia, but its natural history and the factors related to mortality in affected patients are not well understood. METHODS: This retrospective, longitudinal study compared survival in FTLD (n = 177) with Alzheimer disease (AD; n = 395). Hazards analysis investigated the contribution of various demographic, neuropsychiatric, and neuropsychological variables and associated neurologic and neuropathologic findings. RESULTS: The frontotemporal dementia (FTD) subtype of FTLD progressed faster than AD (median survival from retrospectively determined symptom onset, 8.7 +/- 1.2 vs 11.8 +/- 0.6 years, p < 0.0001; median survival from initial clinic presentation, 3.0 +/- 0.5 vs 5.7 +/- 0.1 years, p < 0.0001). Survival was similarly reduced in the related conditions corticobasal degeneration and progressive supranuclear palsy. Survival in the semantic dementia subtype of FTLD (11.9 +/- 0.2 years from onset and 5.3 +/- 0.4 years from presentation), however, was significantly longer than in FTD and did not differ from AD. Hazards analysis to determine factors affecting survival in FTLD showed no effect of age at onset, sex, education, family history, or neuropsychiatric profile. Among neuropsychological measures examined, impaired letter fluency had a significant association with reduced survival. Associated ALS significantly reduced survival in FTLD. The presence of tau-positive inclusions was associated with the slowest progression. CONCLUSIONS: Frontotemporal lobar degeneration progresses more rapidly than Alzheimer disease, and the fastest-progressing cases are those with the frontotemporal dementia clinical subtype, coexisting motor neuron disease, or tau-negative neuropathology.

Age of Onset↗

PubMed2005

Longitudinal volumetric MRI change and rate of cognitive decline.

OBJECTIVE: To examine how baseline and change of volumetric MRI relate to cognitive decline in older individuals. BACKGROUND: Memory is associated with hippocampal integrity, whereas executive function has been linked to impaired frontal lobe function. Previous studies have shown that hippocampal and cortical atrophy are more strongly related to cognition than are measures of subcortical cerebrovascular disease (CVD). The authors hypothesized that memory (MEM) decline would be related to change in hippocampal volume (HC), whereas decline in executive function (EXEC) would be related to change of cortical gray matter volume (CGM) and measures of subcortical CVD. METHODS: Subjects from a multicenter study (n = 103) included cognitively normal, mildly impaired, and demented cases with and without subcortical lacunes. All had longitudinal cognitive evaluation (mean = 4.8 years) and two or more MRI scans at least one year apart (mean = 3.4 years). MRI measures included HC, CGM, total lacune volume (LAC), and white matter hyperintensity volume (WMH). Random effects modeling of longitudinal data assessed effects of MRI baseline and MRI change on baseline and change of psychometrically matched measures of MEM and EXEC. RESULTS: Change in MEM was related to HC baseline and HC change. Change in EXEC was related to baseline CGM and to change in CGM, HC, and LAC. Results were unchanged when demented cases were excluded. WMH was not associated with change in MEM or EXEC independent of HC, CGM, and LAC. CONCLUSION: Hippocampal volume was the primary determinant of memory decline, whereas executive function (EXEC) decline was related to multiple brain components. Results support a hypothesis that MEM decline is strongly influenced by Alzheimer disease (AD), whereas EXEC decline may be complexly determined by cerebrovascular disease and AD.

Aged↗

PubMed2005

A voxel-based morphometry study of patterns of brain atrophy in ALS and ALS/FTLD.

OBJECTIVE: To investigate the patterns of MRI brain atrophy in patients with ALS with and without clinically evident frontotemporal lobar dementia (FTLD) using voxel-based morphometry (VBM). METHODS: Voxel-based morphometry was used to compare T1-weighted MRI images obtained from ten ALS patients with FTLD, ten ALS patients who were cognitively and behaviorally normal, and 22 control subjects. Images from patients and controls were spatially pre-processed using a study-specific, customized template and a priori images. A statistical threshold of p < 0.05 corrected for multiple comparisons determined significance. RESULTS: A common pattern of gray matter atrophy was seen in both ALS and ALS/FTLD patients when compared to controls that involved the bilateral motor/premotor cortices, the left middle and inferior frontal gyri, the anterior portion of the superior frontal gyri, the superior temporal gyri, the temporal poles and left posterior thalamus. Most of the frontal regions were significantly more atrophied in the ALS/FTLD group than in the ALS group. No significant differences were found in white matter volumes. CONCLUSIONS: Patients with ALS and ALS associated with frontotemporal lobar degeneration exhibit widespread gray matter atrophy in frontotemporal regions. This finding supports the idea of a clinical and anatomic continuum between ALS and frontotemporal lobar degeneration.

Adult↗

PubMed2005

The natural history of temporal variant frontotemporal dementia.

BACKGROUND: The temporal variant of frontotemporal dementia (tvFTD) features asymmetric anterior temporal/amygdala degeneration as well as ventromedial frontal, insular, and inferoposterior temporal involvement. Left temporal atrophy has been linked to loss of semantic knowledge, whereas behavioral symptoms dominate the right temporal variant. OBJECTIVE: To investigate the first symptoms and the timing of subsequent symptoms in patients with left versus right tvFTD. METHODS: Twenty-six patients with tvFTD were identified. Six had right > left temporal atrophy (right temporal lobe variant [RTLV]) and were matched with six having comparable left > right temporal atrophy (left temporal lobe variant [LTLV]). Clinical records were reviewed to generate individualized symptom chronologies. RESULTS: In all patients, first symptoms involved semantics (4/6 LTLV, 1/6 RTLV), behavior (4/6 RTLV, 1/6 LTLV), or both (1 LTLV, 1 RTLV). Semantic loss began with anomia, word-finding difficulties, and repetitive speech, whereas the early behavioral syndrome was characterized by emotional distance, irritability, and disruption of physiologic drives (sleep, appetite, libido). After an average of 3 years, patients developed whichever of the two initial syndromes--semantic or behavioral--that they lacked at onset. A third stage, 5 to 7 years from onset, saw the emergence of disinhibition, compulsions, impaired face recognition, altered food preference, and weight gain. Compulsions in LTLV were directed toward visual, nonverbal stimuli, whereas patients with RTLV were drawn to games with words and symbols. CONCLUSIONS: The temporal variant of frontotemporal dementia follows a characteristic cognitive and behavioral progression that suggests early spread from one anterior temporal lobe to the other. Later symptoms implicate ventromedial frontal, insular, and inferoposterior temporal regions, but their precise anatomic correlates await confirmation.

Affective Symptoms↗

PubMed2005

Executive dysfunction in hyperhomocystinemia responds to homocysteine-lowering treatment.

An elevated serum homocysteine level is a risk factor for the development of cognitive impairment. Reported is a late-onset case of hyperhomocystinemia due to a vitamin B12 metabolic deficit (cobalamin C) with cognitive impairment, primarily in frontal/executive function. After homocysteine-lowering therapy, the patient's functional and neuropsychological status improved in conjunction with a decrease in leukoariosis on his MRI scan. These findings suggest that homocysteine-related cognitive impairment may be partially reversible.

Adult↗

PubMed2005

Reduced medial temporal lobe N-acetylaspartate in cognitively impaired but nondemented patients.

BACKGROUND: N-acetylaspartate (NAA) in the medial temporal lobe (MTL) and parietal lobe gray matter (GM) is diminished in Alzheimer disease (AD). Because NAA is considered a marker of neuronal integrity, reduced medial temporal and parietal lobe NAA could be an early indication of dementia-related pathology in elderly individuals. OBJECTIVES: 1) To determine whether cognitively impaired but nondemented (CIND) elderly individuals exhibit a similar pattern of reduced medial temporal and parietal lobe NAA as AD patients. 2) To compare regional NAA patterns, hippocampal and neocortical gray matter (GM) volumes in CIND patients who remained cognitively stable and those who became demented over 3.6 years of follow-up. 3) To examine the relationship between memory performance, medial temporal lobe NAA, and hippocampal volume. METHODS: Seventeen CIND, 24 AD, and 24 cognitively normal subjects were studied using MRSI and MRI. RESULTS: Relative to controls, CIND patients had reduced MTL NAA (19 to 21%, p = 0.005), hippocampal (11 to 14%, p < or = 0.04), and neocortical GM (5%, p = 0.05) volumes. CIND patients who later became demented had less MTL NAA (26%, p = 0.01), hippocampal (17 to 23%, p < or = 0.05), and neocortical GM (13%, p = 0.02) volumes than controls, but there were no significant differences between stable CIND patients and controls. MTL NAA in combination with hippocampal volume improved discrimination of CIND and controls over hippocampal volume alone. In AD and CIND patients, decreased MTL NAA correlated significantly with impaired memory performance. CONCLUSION: Reduced medial temporal lobe N-acetylaspartate, together with reduced hippocampal and neocortical gray matter volumes, may be early indications of dementia-related pathology in subjects at high risk for developing dementia.

Aged↗

PubMed2005

Self awareness and personality change in dementia.

BACKGROUND: Loss of insight is a core diagnostic criterion for frontotemporal dementia (FTD), whereas failure to recognise cognitive deficits and unawareness of disease (anosognosia) are well established findings in Alzheimer's disease (AD). However, self awareness of personality has not been quantified in these patient groups. METHODS: Twenty two patients (12 with frontal variant FTD; 10 with early AD) and 11 older adult normal controls completed self report questionnaires (the Interpersonal Adjectives Scales) describing their current personality. First degree relative informants completed two questionnaires, one describing the subject's current personality, the other retrospectively describing the subject's personality before disease onset. Differences between subject and informant reports of current personality were used to measure the accuracy of self awareness. RESULTS: Discriminant function analysis showed significant differences in self awareness among the three groups, with those in the FTD group showing the greatest magnitude of error in the largest number of personality dimensions (dominance, submissiveness, cold heartedness, introversion, and ingenuousness). Despite personality changes over time, patients with AD showed accurate self awareness in all personality dimensions except submissiveness and extraversion. Normal controls showed a pattern of underestimating positive qualities, whereas patients with FTD exaggerated positive qualities and minimised negative qualities. For the personality facets showing impaired insight, the self reports of patients with FTD and AD most closely matched their premorbid personalities, suggesting a failure to update their self image after disease onset. CONCLUSIONS: This study operationalises research criteria for loss of insight in FTD.

Aged↗

PubMed2004

Behavioral disorders in the frontal and temporal variants of frontotemporal dementia.

OBJECTIVE: To compare the behavioral features and to investigate the neuroanatomic correlates of behavioral dysfunction in anatomically defined temporal and frontal variants of frontotemporal dementia (tvFTD and fvFTD). METHODS: Volumetric measurements of the frontal, anterior temporal, ventromedial frontal cortical (VMFC), and amygdala regions were made in 51 patients with FTD and 20 normal control subjects, as well as 22 patients with Alzheimer disease (AD) who were used as dementia controls. FTD patients were classified as fvFTD or tvFTD based on the relative degree of frontal and anterior temporal volume loss compared with controls. Behavioral symptoms, cerebral volumes, and the relationship between them were examined across groups. RESULTS: Both variants of FTD showed significant increases in rates of elation, disinhibition, and aberrant motor behavior compared with AD. The fvFTD group also showed more anxiety, apathy, and eating disorders, and tvFTD showed a higher prevalence of sleep disturbances than AD. The only behaviors that differed significantly between fvFTD and tvFTD were apathy, greater in fvFTD, and sleep disorders, more frequent in tvFTD. FvFTD was associated with greater frontal atrophy and tvFTD was associated with more temporal and amygdala atrophy compared with AD, but both groups showed significant atrophy in the VMFC compared with AD, which was not associated with VMFC atrophy. In FTD, the presence of many of the behavioral disorders was associated with decreased volume in right-hemispheric regions. CONCLUSION: FvFTD and tvFTD show many similarities in behavior, which appear to be associated with damage to right frontal and temporal structures.

Alzheimer Disease↗

PubMed2004

Higher atrophy rate of entorhinal cortex than hippocampus in AD.

OBJECTIVES: To determine if atrophy rates were higher for entorhinal cortex (ERC) than for hippocampus in Alzheimer disease (AD), to determine the relationship between hippocampal atrophy rate and memory impairment, and to compare atrophy rates of ERC and hippocampus in differentiating between patients with AD and cognitively normal (CN) controls. METHODS: Twenty patients with AD and 25 CN subjects had MRI scans and clinical evaluations twice approximately 1.9 years apart. ERC volumes were measured manually and hippocampal volumes were measured semiautomatically on volumetric T1-weighted MR images. RESULTS: In AD, the atrophy rate of ERC (7.1 +/- 3.2%/year) was higher (p < 0.02) than that of hippocampus (5.9 +/- 2.4%/year). Furthermore, memory deficit in mild AD, measured with the Delayed List Verbal Recall test, correlated significantly with atrophy rates of both ERC (r = -0.61) and hippocampus (r = -0.59). Atrophy rates of ERC and hippocampus were comparable in differentiating between AD and CN. Using atrophy rates of ERC or hippocampus to detect a 20% treatment effect with 90% power (p < 0.05) would require about 100 completed patients per arm in a 2-year study. CONCLUSION: The finding in AD that the atrophy rate in the entorhinal cortex is higher than in the hippocampus is consistent with the view that AD pathology begins in the entorhinal cortex.

Aged↗

PubMed2003

Focal right inferotemporal atrophy in AD with disproportionate visual constructive impairment.

OBJECTIVE: To explore the structural neuroimaging correlates of visual constructive impairment in patients with mild to moderate Alzheimer disease (AD). BACKGROUND: There is considerable heterogeneity in the non-memory cognitive deficits associated with AD. Structural neuroimaging with MRI is an important diagnostic tool that is gaining acceptance as a surrogate measure of brain pathology in AD treatment trials. Most MRI measurements have focused on medial temporal lobe or global cortical atrophy, which may not reflect some important clinical features of AD. METHODS: Thirty-two patients with probable AD were stratified into two groups based on their relative performance on a visual constructive task, the copy of a modified Rey-Osterrieth figure (Rey). The two groups did not differ in basic demographic features or in neuropsychological performance, other than on the visual constructive task. MRI measurements of hippocampal volume, cortical gray matter volume, and focal cortical gray matter loss were performed in the patients and a group of 71 age-matched, normal controls. RESULTS: Both groups showed significant, bilateral hippocampal as well as cortical gray matter volume loss relative to controls. The more spatially impaired AD group (SAD) had more right than left cortical gray matter loss, whereas the opposite was true in the less spatially impaired group (NSAD). The SAD group had significantly less gray matter in the right inferior temporal gyrus relative to the NSAD group. Atrophy of this region was correlated with performance on the Rey task in all patients with AD. CONCLUSIONS: Right inferotemporal atrophy may serve as a neuroimaging marker of visual constructive impairment in mild to moderate AD. Heterogeneous cortical atrophy is a common feature of AD.

Aged↗

PubMed2003

Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD.

OBJECTIVES: 1) To determine the regional pattern of reduced N-acetylaspartate (NAA) in subcortical ischemic vascular dementia (SIVD); 2) to explore the relationship between NAA reduction and subcortical vascular disease; and 3) to test if MR spectroscopic imaging (MRSI) in combination with structural MRI improves differentiation between SIVD and Alzheimer disease (AD). METHODS: Thirteen patients with SIVD (71 +/- 8 years old) and 43 patients with AD of comparable age and dementia severity were studied using MRSI and MRI. Patients were compared to 52 cognitively normal subjects with and without lacunes. RESULTS: Compared to controls, patients with SIVD had lower NAA by 18% (p < 0.001) in frontal cortex and by 27% (p < 0.003) in parietal cortex, but no significant NAA reduction in white matter and medial temporal lobe. Compared to patients with AD, patients with SIVD had lower NAA by 13% (p < 0.02) in frontal cortex and by 20% (p < 0.002) in left parietal cortex. Cortical NAA decreased in SIVD with increasing white matter lesions (r = 0.54, p < 0.02) and number of lacunes (r = 0.59, p < 0.02). Thalamic lacunes were associated with greater NAA reduction in frontal cortex than were lacunes outside the thalamus (p < 0.02) across groups, after adjusting for cognitive impairments. Adding parietal NAA to MRI-derived hippocampal atrophy improved separation between SIVD and AD (p = 0.02) from 79 to 89%. CONCLUSIONS: These results emphasize the importance of cortical dysfunction as a factor in SIVD and indicate a characteristic pattern of metabolite change that might serve as a basis for improved diagnosis.

Aged↗

PubMed2003

DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To compare the efficacy and tolerability of dehydroepiandrosterone (DHEA) vs placebo in AD. METHOD: Fifty-eight subjects with AD were randomized to 6 month's treatment with DHEA (50 mg per os twice a day; n = 28) or placebo (n = 30) in a multi-site, double-blind pilot trial. Primary efficacy measures assessed cognitive functioning (the AD Assessment Scale-Cognitive [ADAS-Cog]) and observer-based ratings of overall changes in severity (the Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus]). At baseline, 3 months, and 6 months, the ADAS-Cog was administered, and at 3 and 6 months, the CIBIC-Plus was administered. The 6-month time point was the primary endpoint. RESULTS: Nineteen DHEA-treated subjects and 14 placebo-treated subjects completed the trial. DHEA was relatively well-tolerated. DHEA treatment, relative to placebo, was not associated with improvement in ADAS-Cog scores at month 6 (last observation carried forward; p = 0.10); transient improvement was noted at month 3 (p = 0.014; cutoff for Bonferroni significance = 0.0125). No difference between treatments was seen on the CIBIC-Plus at either the 6-month or the 3-month time points. CONCLUSIONS: DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance.

Aged↗

PubMed2003

Are amyotrophic lateral sclerosis patients cognitively normal?

BACKGROUND: Patients with ALS are often told that the disease spares cognition; however, recent evidence suggests deficits in frontal executive skills occur in a sizable minority of ALS patients. In many instances, the frontal executive deficits represent the co-occurrence of frontotemporal lobar dementia (FTLD) and ALS. METHODS: Word generation, a simple frontal task that takes <2 minutes, was tested in 100 consecutive patients with ALS seen in the authors' multidisciplinary clinic. Any patient with a prior dementia diagnosis was excluded from the study. A subset of 44 patients agreed to undergo further neuropsychological testing and clinical interview to confirm or deny a diagnosis of dementia. RESULTS: Diminished word generation was found in one-third. Of the patients with abnormal word generation who agreed to further evaluation, nearly all were shown to meet research criteria for FTLD. In addition, one-quarter of the patients with normal word generation who agreed to further evaluation met research criteria for FTLD; these patients had new-onset personality changes. CONCLUSIONS: This study suggests that frontal executive deficits are present in half of ALS patients, many of whom meet strict research criteria for FTLD. Word generation tests are a useful screening tool in this cohort.

Adult↗

PubMed2003

Atrophy rates of entorhinal cortex in AD and normal aging.

OBJECTIVES: To explore the atrophy rate of entorhinal cortex (ERC) in AD and normal aging and assess the value of rate measurement of ERC atrophy for classifying subjects with AD from cognitively normal (CN) control subjects. METHODS: Twenty-one AD patients and 23 CN subjects had MRI scans and clinical evaluations twice within 1.8 +/- 0.6 years. ERC volumes were manually measured on volumetric T1-weighted MR images. RESULTS: Patients with AD had a greater annual percentage volume change of ERC than CN subjects on both sides (left: 6.8 +/- 4.3%/year for AD vs 1.4 +/- 2.5%/year for CN [F(1,42) = 25.6, p < 0.001]; right: 6.3 +/- 3.3%/year for AD vs 1.4 +/- 2.3%/year for CN [F(1,42) = 25.6, p < 0.001]). Furthermore, increased ERC atrophy rate was correlated (r = -0.56, p = 0.01) with decreased memory performance in AD. CN subjects had on average annual ERC atrophy rates greater than zero (p < 0.01). Baseline volume of ERC predicted atrophy rate of ERC (left: r = -0.53, p < 0.01; right: r = -0.42, p < 0.05) in CN subjects but not in AD subjects. Using ERC baseline volumes alone resulted in 77% overall correct classification (p < 0.01) between AD and CN subjects, with 76% sensitivity and 78% specificity and an area under receiver operator characteristic (ROC) curve of 0.83. Adding annual atrophy rate of ERC to the model accounted for most of the variance (p < 0.01), diminishing contributions from baseline volume and yielding 82% overall classification, with 76% sensitivity and 86% specificity and an area under the ROC curve of 0.93. CONCLUSION: ERC volume loss over time may be a better indicator for AD than cross-sectional measurements.

Aged↗