Biomedical subjects

Bruce L Miller

Publications and source records attributed to Bruce L Miller.

At least 37 records · Page 2Linked to original sources

PubMed2006

An overview on Primary Progressive Aphasia and its variants.

We present a review of the literature on Primary Progressive Aphasia (PPA) together with the analysis of neuropschychological and neuroradiologic profiles of 42 PPA patients. Mesulam originally defined PPA as a progressive degenerative disorder characterized by isolated language impairment for at least two years. The most common variants of PPA are: 1) Progressive nonfluent aphasia (PNFA), 2) semantic dementia (SD), 3) logopenic progressive aphasia (LPA). PNFA is characterized by labored speech, agrammatism in production, and/or comprehension. In some cases the syndrome begins with isolated deficits in speech. SD patients typically present with loss of word and object meaning and surface dyslexia. LPA patients have word-finding difficulties, syntactically simple but accurate language output and impaired sentence comprehension. The neuropsychological data demonstrated that SD patients show the most characteristic pattern of impairment, while PNFA and LPA overlap within many cognitive domains. The neuroimaging analysis showed left perisylvian region involvement. A comprehensive cognitive, neuroimaging and pathological approach is necessary to identify the clinical and pathogenetic features of different PPA variants.

Aged↗

PubMed2006

Acquired extroversion associated with bitemporal variant of frontotemporal dementia.

Frontotemporal dementia (FTD) is characterized by alterations in personality. The nature of the personality changes depend on the localization of the pathology. The authors present three patients with acquired extroversion who met criteria for FTD. All three patients exhibited predominant bilateral temporal involvement as determined with functional neuroimaging. Possible mechanisms for acquired extroversion in bitemporal FTD include bilateral amygdalar damage with decreased interpersonal fear or sense of threat, orbitofrontal-ventromedial damage with social disinhibition, and relative sparing of dorsolateral frontal and anterior cingulate regions with preserved interpersonal agency. FTD can be a vehicle for unraveling the basis of personality characteristics such as the introversion/extroversion dimension.

Aged↗

PubMed2005

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus.

Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.

Allergens↗

PubMed2005

Clinical and neuropsychological features of corticobasal degeneration.

In this paper, we review the history, clinical, cognitive, imaging and neuropathological features of corticobasal degeneration (CBD). Additionally, we report new findings on the neuropsychological profile of 14 patients with CBD compared to 14 with Alzheimer's disease. Increasing awareness of this disorder has led to the realization that specific cognitive and imaging changes are common with CBD degeneration and that these changes help with clinical diagnosis.

Alzheimer Disease↗

PubMed2005

Neuroanatomical correlates of behavioural disorders in dementia.

Neurodegenerative diseases are associated with profound changes in social and emotional function. The emergence of increasingly sophisticated methods for measuring brain volume has facilitated correlation of local changes in tissue content with cognitive and behavioural changes in neurodegenerative disease. The current study examined neuroanatomical correlates of behavioural abnormalities, as measured by the Neuropsychiatric Inventory, in 148 patients with dementia using voxel-based morphometry. Of 12 behaviours examined, 4 correlated with tissue loss: apathy, disinhibition, eating disorders and aberrant motor behaviour. Increasing severity across these four behaviours was associated with tissue loss in the ventral portion of the right anterior cingulate cortex (vACC) and adjacent ventromedial superior frontal gyrus (vmSFG), the right ventromedial prefrontal cortex (VMPC) more posteriorly, the right lateral middle frontal gyrus, the right caudate head, the right orbitofrontal cortex and the right anterior insula. In addition, apathy was independently associated with tissue loss in the right vmSFG, disinhibition with tissue loss in the right subgenual cingulate gyrus in the VMPC, and aberrant motor behaviour with tissue loss in the right dorsal ACC and left premotor cortex. These data strongly support the involvement of the right hemisphere in mediating social and emotional behaviour and highlight the importance of distinct regions on the medial wall of the right frontal lobe in regulating different behaviours. Furthermore, the findings underscore the utility of studying patients with dementia for understanding the neuroanatomical basis of social and emotional functions.

Aged↗

PubMed2005

Neuroanatomical correlates of impaired recognition of emotion in dementia.

Neurodegenerative diseases frequently affect brain regions important for emotional processing, offering a valuable opportunity to study the effects of brain injury on emotion. The current study examined the neuroanatomical correlates of impaired recognition of emotions in patients with neurodegenerative disease. Performance on recognition of facial expressions, as measured by the Florida Affect Battery, was correlated with regional changes in gray matter tissue content in 50 patients with neurodegenerative disease using voxel-based morphometry. Recognition accuracy in the group was poor for negative emotions (fear, anger and sadness) and good for happiness, consistent with previous studies. For negative emotions, a region in the right lateral inferior temporal gyrus (Brodman's area (BA) 20) extending into the right middle temporal gyrus (BA 21) was correlated with accuracy. This effect appeared to be strongest for sadness, which was also independently correlated with atrophy in the superior temporal gyrus. These data suggest that regions in the right lateral and inferolateral temporal lobe are important for visual processing of negative emotions from faces and that functioning of this right temporal network is most critical for recognition of sad faces.

Aged↗

PubMed2005

Acquired sociopathy and frontotemporal dementia.

BACKGROUND: It is not understood why some patients with frontotemporal dementia (FTD) manifest sociopathic behavior. OBJECTIVE: To examine the prevalence and characteristics of sociopathic behavior in FTD patients as compared to those with Alzheimer's disease (AD). METHODS AND PARTICIPANTS: We surveyed a group of FTD patients and a group of AD patients for sociopathic behavior, evaluated the characteristics surrounding their acts, and compared the groups on neuropsychological tests and functional neuroimaging. Twenty-eight outpatients with FTD (15 men, 13 women; 61.9+/-7.1 years; Mini-Mental State Examination score 23.6+/-8.1) were compared with 28 patients with clinically probable AD (13 men, 15 women; 66.1+/-9.2 years; Mini-Mental State Examination score 21.3 +/- 5.3). Main outcome measures included: (a) the prevalence of sociopathic acts; (b) a structured interview; (c) neuropsychological tests including the Frontal Assessment Battery, and (d) clinically obtained positron emission tomography or single photon emission tomography scans. RESULTS: Sixteen (57%) of the FTD patients had sociopathic behavior compared to two (7%) of the AD patients (chi(2)=13.84, p<0.001). Sociopathic acts among FTD patients included unsolicited sexual acts, traffic violations, physical assaults, and other unacceptable behaviors. On interview, the FTD patients with sociopathic acts were aware of their behavior and knew that it was wrong but could not prevent themselves from acting impulsively. They claimed subsequent remorse, but they did not act on it or show concern for the consequences. Among FTD patients with sociopathy, neuropsychological assessment showed impaired motor inhibition, and functional neuroimaging showed right frontotemporal involvement. CONCLUSION: The results suggest that sociopathy in FTD results from a combination of diminished emotional concern for the consequences of their acts and disinhibition consequent to right frontotemporal dysfunction. In many jurisdictions, FTD patients with sociopathy would not pass legal criteria for 'not guilty by reason of insanity'.

Aged↗

PubMed2005

Age effects on atrophy rates of entorhinal cortex and hippocampus.

The effects of age, subcortical vascular disease, apolipoprotein E (APOE) epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04+/-0.02% per year for ERC and 0.05+/-0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE epsilon4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials.

Aged↗

PubMed2005

Diagnosis of human prion disease.

With the discovery of the prion protein (PrP), immunodiagnostic procedures were applied to diagnose Creutzfeldt-Jakob disease (CJD). Before development of the conformation-dependent immunoassay (CDI), all immunoassays for the disease-causing PrP isoform (PrPSc) used limited proteolysis to digest the precursor cellular PrP (PrPC). Because the CDI is the only immunoassay that measures both the protease-resistant and protease-sensitive forms of PrPSc, we used the CDI to diagnose human prion disease. The CDI gave a positive signal for PrPSc in all 10-24 brain regions (100%) examined from 28 CJD patients. A subset of 18 brain regions from 8 patients with sporadic CJD (sCJD) was examined by histology, immunohistochemistry (IHC), and the CDI. Three of the 18 regions (17%) were consistently positive by histology and 4 of 18 (22%) by IHC for the 8 sCJD patients. In contrast, the CDI was positive in all 18 regions (100%) for all 8 sCJD patients. In both gray and white matter, approximately 90% of the total PrPSc was protease-sensitive and, thus, would have been degraded by procedures using proteases to eliminate PrPC. Our findings argue that the CDI should be used to establish or rule out the diagnosis of prion disease when a small number of samples is available as is the case with brain biopsy. Moreover, IHC should not be used as the standard against which all other immunodiagnostic techniques are compared because an immunoassay, such as the CDI, is substantially more sensitive.

Biopsy↗

PubMed2005

Fluent versus nonfluent primary progressive aphasia: a comparison of clinical and functional neuroimaging features.

To better characterize fluent and nonfluent variants of primary progressive aphasia (PPA). Although investigators have recognized both fluent and nonfluent patients with PPA, the clinical and neuroimaging features of these variants have not been fully defined. We present clinical and neuropsychological data on 47 PPA patients comparing the fluent (n=21) and nonfluent (n=26) subjects. We further compared language features with PET/SPECT data available on 39 of these patients. Compared to the nonfluent PPA patients, those with fluent PPA had greater impairment of confrontational naming and loss of single word comprehension. They also exhibited semantic paraphasic errors and loss of single word comprehension. Patients with nonfluent PPA were more likely to be female, were more often dysarthric, and exhibited phonological speech errors in the absence of semantic errors. No significant differences were seen with regard to left hemisphere abnormalities, suggesting that both variants result from mechanisms that overlap frontal, temporal, and parietal regions. Of the language measures, only semantic paraphasias were strongly localized, in this case to the left temporal lobe. Fluent and nonfluent forms of PPA are clinically distinguishable by letter fluency, single word comprehension, object naming, and types of paraphasic errors. Nevertheless, there is a large amount of overlap between dysfunctional anatomic regions associated with these syndromes.

Aged↗

PubMed2005

Presenilin 1 Glu318Gly polymorphism: interpret with caution.

BACKGROUND: The significance of the presenilin 1 (PSEN1) Glu318Gly polymorphism has been described as either a causal mutation with reduced penetrance or a benign polymorphism. When this polymorphism is found in a symptomatic person with a family history of dementia, counseling on recurrence risk becomes very problematic. OBJECTIVE: To demonstrate that the PSEN1 Glu318Gly polymorphism should be interpreted cautiously. DESIGN: Case histories of 2 patients with presenile dementia and family histories of dementia are described. The PSEN1 gene was sequenced in the patients and in 11 family members of patient 1. RESULTS: Two patients with presenile dementia and personality change were found to carry the PSEN1 Glu318Gly polymorphism. The presence of the polymorphism was confirmed in several family members of patient 1 but was absent in 1 symptomatic relative. CONCLUSIONS: The Glu318Gly polymorphism may be associated with risk for neurodegenerative disease; however, in the cases described here, it did not appear to be a risk factor. Until there is consensus on whether it is associated with disease, families should be informed that the clinical significance of the polymorphism is uncertain.

Alzheimer Disease↗

PubMed2005

Frontotemporal lobar degeneration: demographic characteristics of 353 patients.

BACKGROUND: Until recently, frontotemporal lobar degeneration (FTLD) was considered a rare neurodegenerative disorder that was difficult to diagnose. The publication of consensus criteria for FTLD, however, prompted systematic studies. The criteria categorize FTLD into 3 subgroups: frontotemporal dementia, semantic dementia, and progressive nonfluent aphasia. OBJECTIVE: To compare demographic characteristics of patients in the 3 FTLD subgroups. DESIGN: We compared diagnostic breakdown, age at onset, sex, Mini-Mental State Examination score at first visit, education, and neuropathological diagnoses in a large sample of FTLD patients from 3 different university dementia clinics, including 2 neurologic clinics in the United States and 1 psychiatric clinic in Germany. RESULTS: The frontotemporal dementia subgroup represented approximately half of all FTLD diagnoses. Patients diagnosed as having frontotemporal dementia (mean age, 57.5 years) and semantic dementia (mean age, 59.3 years) had an earlier age at onset than patients diagnosed as having progressive nonfluent aphasia (mean age, 63.0 years). There were significantly more men diagnosed as having frontotemporal dementia (63.5%) and semantic dementia (66.7%) when compared with progressive nonfluent aphasia (39.1%) (P = .005 for frontotemporal dementia vs progressive nonfluent aphasia and P = .002 for semantic dementia vs progressive nonfluent aphasia). Generally, the demographic features and diagnostic categories of the patient populations across the 3 sites were comparable. There were 68 deaths and 37 autopsies. Frontotemporal lobar degeneration with ubiquitin-positive tau-negative inclusions (48.5%), dementia lacking distinctive histopathological features (18.2%), and Pick disease (15.2%) were the most common neuropathological diagnoses. CONCLUSIONS: These findings show that cohorts of patients can be combined using new research criteria for FTLD and demonstrate striking demographic differences among FTLD subgroups. The sex and age-at-onset differences suggest that there may be biological differences among FTLD subgroups. In this sample, FTLD with ubiquitin-positive inclusions accounted for half of all neuropathological diagnoses.

Adult↗

PubMed2005

Patterns of autobiographical memory loss in dementia.

BACKGROUND: Several studies have found impaired recall of remote autobiographical memories relative to recent memories in semantic dementia (SD), a pattern opposite to that in Alzheimer's disease (AD). OBJECTIVE: To document dissociation of memory for autobiographical incidents and personal semantic information in individuals with AD, frontotemporal dementia (FTD), and SD. METHODS: The authors administered the Autobiographical Memory Interview to eight individuals with AD, 11 with FTD, eight with SD, and eight normal controls . Autobiographical incidents and personal semantic memory was assessed from three time periods: childhood, early adulthood, and recent life. RESULTS: Individuals with SD recalled more details of autobiographical incidents from the most recent 5 years than from childhood and early adulthood (childhood vs recent life: t(7) = -3.59, p = 0.009; early adulthood vs recent life: t(7) = -4.33, p = 0.003). No difference was found between childhood and early adulthood (t(7) = 1.11, p = 0.305). Recall of personal semantic information was related to the age of the memory with less remembered from earlier time periods (childhood vs recent life: t(7) = -6.52, p < 0.001; childhood vs early adulthood: t(7) = -2.61, p = 0.035; early adulthood vs recent life: t(7) = -9.15, p < 0.001). CONCLUSIONS: SD is a compelling model in which to study the anatomy of episodic memory.

Aged↗

PubMed2005

Stereotypical movements and frontotemporal dementia.

Stereotypical movements are characteristic of autism or mental retardation but can also occur in patients with dementia, particularly frontotemporal dementia (FTD). In this study, we administered the Abnormal Involuntary Movement Scale (AIMS) to 18 patients with FTD and to 18 patients with the most common form of dementia, Alzheimer's disease (AD). The AIMS scores were gathered at the initial presentation of patients who had not received antipsychotic medications. Compared to the AD patients, the FTD patients had significantly more stereotypical movements, including frequent rubbing behaviors and some self-injurious acts. All the FTD patients with stereotypical movements had compulsive-like behaviors, suggesting a similar pathophysiologic cause, and most had a decrease in their stereotypical movements with the administration of sertraline, a serotonin selective reuptake inhibitor.

Aged↗

PubMed2005

White matter lesions are associated with cortical atrophy more than entorhinal and hippocampal atrophy.

The goal of this study was to examine the relationship between subcortical vascular disease and brain atrophy in patients with Alzheimer's disease (AD) and mixed dementia (i.e., AD and subcortical vascular disease together). MRI was performed on 77 cognitively normal (CN) subjects, 50 AD and 13 mixed dementia patients. Subcortical vascular disease was determined by white matter hyperintensities (WMH) volume and presence of subcortical lacunes. Brain atrophy was measured using total brain cortical gray matter (CGM), entorhinal cortex (ERC) and hippocampal volumes. CGM volume, but not ERC or hippocampal volume was inversely related to WMH volume in patients and controls. In contrast, no relationship was detected between CGM, ERC, or hippocampal volumes and subcortical lacunes. Furthermore, no interaction was found between WMH and diagnosis on cortical atrophy, implying that WMH affect cortical atrophy indifferently of group. These results suggest that subcortical vascular disease, manifested as WMH, may affect cortical atrophy more than ERC and hippocampal atrophy. Further, AD pathology and subcortical vascular disease may independently affect cortical atrophy.

Aged↗

PubMed2005

Dissociations in hippocampal and frontal contributions to episodic memory performance.

The hippocampus and frontal lobes both contribute to episodic memory performance. In the present study, the authors evaluated the relative contributions of hippocampus, frontal lobes, anterior temporal cortex, and posterior cortex to memory performance in neurodegenerative patients and normal older controls. Subjects (n=42) were studied with structural MRI and a memory paradigm that measured delayed recall, semantic clustering during recall, recognition discriminability, and recognition response bias. Data were analyzed with multiple regression. Consistent with the authors' hypotheses, hippocampal volumes were the best predictor of delayed recall and recognition discriminability, whereas frontal volumes were the best predictor of semantic clustering and response bias. Smaller frontal volumes were associated with less semantic clustering during recall and a more liberal response bias. Results indicate that hippocampal and frontal contributions to episodic memory can be dissociated, with the hippocampus more important for memory accuracy, and frontal structures more important for strategic processing and decision making.

Aged↗

PubMed2005

Patterns of cognitive and emotional empathy in frontotemporal lobar degeneration.

OBJECTIVE: To examine the relationship between empathy and cognition in frontotemporal lobar degeneration (FTLD). BACKGROUND: Theoretical models suggest empathy has multiple cognitive and affective subcomponents, and recent studies suggest that performance on specific cognitive tests may predict empathy. Qualitative behavioral studies of patients with FTLD suggest empathy loss may occur directly as a result of damage to frontal and temporal structures. METHOD: First-degree relatives used the Interpersonal Reactivity Index (IRI), a measure of cognitive and emotional empathy, to rate 18 patients with frontotemporal dementia (FTD), 19 patients with semantic dementia (SD), 16 patients with Alzheimer disease (AD), and 10 age-matched healthy control subjects (NC). Subjects also underwent cognitive testing. RESULTS: Both FTD and SD groups showed significantly lower levels of empathy than either ADs or NCs. SDs showed disruption of both emotional and cognitive empathy, whereas FTDs showed only disruption of cognitive empathy. Regressions controlling for general cognitive impairment showed 32% of the variance in Perspective Taking score was predicted by Category Fluency (P < 0.001), and 25% of the variance in Fantasy score was accounted for by Phonemic Fluency (P < 0.001). CONCLUSIONS: Although cognitive empathy is at least partly reliant on frontal structures, the emotional components of empathy are likely mediated by structures in the temporal lobes.

Aged↗

PubMed2005

Pattern of cerebral hypoperfusion in Alzheimer disease and mild cognitive impairment measured with arterial spin-labeling MR imaging: initial experience.

PURPOSE: To prospectively determine if pulsed arterial spin-labeling perfusion magnetic resonance (MR) imaging depicts regional cerebral hypoperfusion in subjects with Alzheimer disease (AD) and mild cognitive impairment (MCI), compared with perfusion in cognitively normal (CN) subjects, that is consistent with results of fluorodeoxyglucose (FDG) positron emission tomography (PET) and hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) studies of similar populations. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty subjects with AD (13 men, seven women; mean age, 72.9 years), 18 with MCI (nine men, nine women; mean age, 73.3 years), and 23 CN subjects (10 men, 13 women; mean age, 72.9 years) underwent arterial spin-labeling and volumetric T1-weighted structural MR imaging. Perfusion images were coregistered to structural images, corrected for partial volume effects (PVEs) with information from the structural image to determine tissue content of perfusion voxels, and normalized to a study-specific template. Analyses of perfusion differences between groups, with and without corrections for PVEs, were performed on a voxel-by-voxel basis with a one-tailed fixed-effects analysis of covariance model adjusted for age. In addition, tests were performed with and without accounting for global perfusion. RESULTS: The AD group showed significant regional hypoperfusion, compared with the CN group, in the right inferior parietal cortex extending into the bilateral posterior cingulate gyri (P <.001), bilateral superior and middle frontal gyri (P <.001), and left inferior parietal lobe (P=.007). When PVEs from underlying cortical gray matter atrophy were accounted for, the AD group still showed hypoperfusion in the right inferior parietal lobe extending into the bilateral posterior cingulate gyri (P <.001) and left (P=.003) and right (P=.012) middle frontal gyri. With a more liberal voxel-level threshold of P <.01, the MCI group showed significant regional hypoperfusion relative to the CN group in the inferior right parietal lobe (P=.046), similar to the region of greatest significance in the AD group. CONCLUSION: Arterial spin-labeling MR imaging showed regional hypoperfusion with AD, in brain regions similar to those seen in FDG PET and HMPAO SPECT studies of similar populations; this hypoperfusion persists after accounting for underlying cortical gray matter atrophy.

Aged↗