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Biomedical subjects

Sandra Black

Publications and source records attributed to Sandra Black.

16 recordsLinked to original sources
PubMed2007

Structural imaging reveals anatomical alterations in inferotemporal cortex in congenital prosopagnosia.

Congenital prosopagnosia (CP) refers to the lifelong impairment in face recognition in individuals who have intact low-level visual processing, normal cognitive abilities, and no known neurological disorder. Although the face recognition impairment is profound and debilitating, its neural basis remains elusive. To investigate this, we conducted detailed morphometric and volumetric analyses of the occipitotemporal (OT) cortex in a group of CP individuals and matched control subjects using high-spatial resolution magnetic resonance imaging. Although there were no significant group differences in the depth or deviation from the midline of the OT or collateral sulci, the CP individuals evince a larger anterior and posterior middle temporal gyrus and a significantly smaller anterior fusiform (aF) gyrus. Interestingly, this volumetric reduction in the aF gyrus is correlated with the behavioral decrement in face recognition. These findings implicate a specific cortical structure as the neural basis of CP and, in light of the familial history of CP, target the aF gyrus as a potential site for further, focused genetic investigation.

Adult↗
PubMed2007

Specific symptomatic changes following donepezil treatment of Alzheimer's disease: a multi-centre, primary care, open-label study.

BACKGROUND: Standard measurement scales used in anti-dementia trials may not capture symptomatic changes recognized by clinicians and caregivers. We studied a symptom checklist, completed separately by caregivers and by clinicians, to identify patterns of change associated with donepezil treatment. METHODS: In a multi-centre, 6-month, open-label study of 101 primary care patients, changes in a 19-symptom checklist were assessed in relation to changes in standardized scales of cognition, activities of daily living, behavior, and caregiver burden. RESULTS: Three symptoms were reported in more than 80% of patients by both clinicians and caregivers: problems in remembering, (97%), temporal orientation (89%), and repetitiveness (85%). Five others overlapped on each of the clinician and caregiver 'top ten', including cognitive activation, spatial orientation, leisure, attention, and apathy. Clinicians reported that symptoms did not improve in 38 patients, whereas there was some improvement in 43, and improvement in most symptoms in 20. Caregivers reported that symptoms did not improve in 55 patients, whereas 27 and 19 patients showed some and most symptoms improving respectively. Patients with the greatest symptomatic improvement also improved most on the ADAS-Cog and the other standardized measures, whereas no improvement (or decline) in each standardized measure was observed in people whose symptoms worsened or did not improve. CONCLUSION: A symptom checklist allowed clinically meaningful profiles to be identified, but revealed different estimates of response between clinicians and caregivers. Both agreed that improved executive function was the most common response. A symptom checklist can help translate between standard measures and everyday practice.

Activities of Daily Living↗
PubMed2007

Cognitive rehabilitation in the elderly: a randomized trial to evaluate a new protocol.

This study provides an introduction to, and overview of, several papers that resulted from a randomized control trial that evaluated a new cognitive rehabilitation protocol. The program was designed to improve general strategic abilities in ways that would be expressed in a broad range of functional domains. The trial, which was conducted on a sample of older adults who had experienced normal age-related cognitive decline, assessed performance in the following domains: memory, goal management, and psychosocial status. The general rationale for the trial, the overall experimental design, and the approach to statistical analyses that are relevant to each paper are described here. The results for each functional domain are reported in separate papers in this series.

Aged↗
PubMed2007

Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.

Aged↗
PubMed2006

Disease progression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study.

BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and behavioural outcomes in patients with VCI to patients with no cognitive impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi-centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients, 938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at baseline. Compared to people with NCI, of whom 20-40% showed progression based on cognitive and functional measures, those with VCI were more likely to progress (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed progression of affective symptoms (30%) than those with NCI (12%) or AD (15% p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most people with VCI show readily detectable progression by 30 months. Depressive symptoms were more common and more progressive in VCI than in Alzheimer's disease, whereas clinical evidence of progressive executive dysfunction was common in both AD and VCI.

Aged↗
PubMed2006

Novel splicing mutation in the progranulin gene causing familial corticobasal syndrome.

Corticobasal syndrome (CBS) is a rare cognitive and movement disorder characterized by asymmetric rigidity, apraxia, alien-limb phenomenon, cortical sensory loss, myoclonus, focal dystonia, and dementia. It occurs along the clinical spectrum of frontotemporal lobar degeneration (FTLD), which has recently been shown to segregate with truncating mutations in progranulin (PGRN), a multifunctional growth factor thought to promote neuronal survival. This study identifies a novel splice donor site mutation in the PGRN gene (IVS7+1G-->A) that segregates with CBS in a Canadian family of Chinese origin. We confirmed the absence of the mutant PGRN allele in the RT-PCR product which supports the model of haploinsufficiency for PGRN-linked disease. This report of mutation in the PGRN gene in CBS extends the evidence for genetic and phenotypic heterogeneity in FTLD spectrum disorders.

Apraxias↗
PubMed2006

Elderly patients with hip fracture with positive affect have better functional recovery over 2 years.

OBJECTIVES: To evaluate whether patients with hip fracture with high positive affect had better functioning than those with low positive affect or depressive symptoms in three performance-based measures over 2 years after the fracture. DESIGN: Longitudinal study with assessments at baseline and 2, 6, 12, 18, and 24 months posthospitalization. SETTING: Community. PARTICIPANTS: Four hundred thirty-two patients, aged 65 and older, hospitalized for hip fracture in Baltimore, Maryland, between 1990 and 1991. MEASUREMENTS: High and low positive affect and depressive symptoms were based on baseline Center for Epidemiologic Studies Depression Scale score, usual and rapid walking speed, one chair stand, demographic factors, comorbidities, and history of cognitive impairment. RESULTS: At each follow-up point, respondents with high positive affect at baseline (36% of sample) had faster walking and chair stand speeds than those with low positive affect (13%) and depressive symptoms (51%). For example, at 6 months, the mean usual walking pace was 0.4 m/s (standard error (SE)=0.02) for respondents with high positive affect, versus 0.4 m/s (SE=0.03) and 0.35 m/s (SE=0.02) for patients with low positive affect and depressive symptoms, respectively; adjusted differences were 0.02 (95% confidence interval (CI)=-0.06-0.09) and 0.06 (95% CI=0.01-0.11). Respondents with high positive affect appeared to achieve their maximum improvement in usual pace approximately 6 months before other respondents, but this interaction was not statistically significant. Respondents with consistently high positive affect had the best functioning over the follow-up period. CONCLUSION: High positive affect seems to have a beneficial influence on performance-based functioning after hip fracture.

Affect↗
PubMed2006

Telestroke: a multi-site, emergency-based telemedicine service in Ontario.

A telestroke service was established in Ontario in 2002. Six neurologists on four campuses of two academic health centres of the University of Toronto participated in the call roster to support emergency physicians in two northern cities, North Bay and Sudbury. Videoconferencing units were provided in the hospitals and in the homes of the neurologists. PC workstations were used to access computed tomography (CT) images. In the first 34 months' operation, a total of 88 patient consultations were conducted. Twenty-six patients received tissue plasminogen activator (t-PA). Although the number of consultations was relatively low, the feasibility of telemedicine for acute stroke care was demonstrated. The economics remain to be explored. The telestroke model is a viable alternative to the provision of acute stroke care for communities that have CT scanners, but no access to a resident neurologist.

Emergency Medical Services↗
PubMed2005

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory.

Amnesia↗
PubMed2004

Pantomime and imitation of limb gestures in relation to the severity of Alzheimer's disease.

The present study was designed to investigate the relationship between performance of limb gestures and the severity of Alzheimer's disease (A.D.). Apraxia tends to occur at later stages of A.D., and the severity of apraxia has been shown to vary with the severity of A.D. dementia. Participants were 19 mild (including 9 with no cognitive impairment and 10 with mild impairment) and 18 moderate A.D. patients as well as 25 controls and they were asked to pantomime (P) or imitate (both concurrent (CI) and delayed (DI)), eight transitive gestures to assess praxis performance. Results indicated that the moderate patients performed less accurately than mild and non-impaired patients, and that across all groups, the imitation conditions were performed less accurately than pantomime, relative to controls. Correlational analyses revealed that MMSE scores were correlated with all three performance conditions suggesting that impaired praxis performance may relate to more global impairment. Finally, a frequency analysis was conducted to examine whether A.D. patients showed patterns of apraxia as described in Roy's model (1996). Results indicated that A.D. patients showed greatest impairment on pattern 7 (deficits in P, DI, and CI), reflecting late-stage gesture production, with a greater frequency of moderate patients exhibiting each apraxic pattern.

Aged↗
PubMed2004

A set of observational measures for rating support and participation in conversation between adults with aphasia and their conversation partners.

Conversation partners of individuals with aphasia, including health care professionals, families, and others, play a role that is as important for communication as the language disorder suffered by individuals with aphasia. Two complementary measures designed to capture elements of conversation between adults with aphasia and their speaking conversation partners have been developed. The first measure provides an index of the conversation partner's skill in providing conversational support. The second provides an index of the level of participation in conversation by the person with aphasia. This article describes the development of the measures, including preliminary psychometric data, and discusses applications.

Adult↗
PubMed2003

Efficacy and tolerability of donepezil in vascular dementia: positive results of a 24-week, multicenter, international, randomized, placebo-controlled clinical trial.

BACKGROUND AND PURPOSE: Clinical observations suggest that patients with vascular dementia (VaD) may benefit from treatment with cholinesterase inhibitors. This study evaluated the efficacy and safety of donepezil for relieving symptoms of dementia in VaD. METHODS: Patients (n=603; mean age, 73.9 years; 55.2% men) with probable (70.5%) or possible (29.5%) VaD, according to criteria of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), were randomized to 24 weeks of treatment with donepezil 5 mg/d (n=198), donepezil 10 mg/d (5 mg/d for first 28 days; n=206), or placebo (n=199). Analyses were based on the intent-to-treat population. RESULTS: At week 24, both donepezil groups showed significant improvement in cognition versus placebo on the Alzheimer's Disease Assessment Scale-cognitive subscale (mean change from baseline score effect size: donepezil 5 mg/d, -1.90; P=0.001; donepezil 10 mg/d, -2.33; P<0.001). Significant improvements in patients' global function were seen versus placebo at week 24 (observed cases), on the Clinician's Interview-Based Impression of Change-Plus version only for patients on donepezil 5 mg/d (P=0.014), and on the Sum of the Boxes of the Clinical Dementia Rating only for patients on 10 mg/d (P=0.007). Donepezil-treated patients showed significant benefits in activities of daily living over placebo on the Alzheimer's Disease Functional Assessment and Change Scale (mean change from baseline score effect size at week 24: donepezil 5 mg/d, -1.31, P=0.02; donepezil 10 mg/d, -1.31, P=0.02). Donepezil was well tolerated. Withdrawal rates due to adverse events were relatively low (placebo, 11.1%; donepezil 5 mg/d, 11.1%; donepezil 10 mg/d, 21.8%; P=0.005 versus placebo). CONCLUSIONS: These data demonstrate that donepezil is an effective and well-tolerated treatment for VaD and show it may have an important place in the management of this condition.

Activities of Daily Living↗
PubMed2003

Phase I trial of perillyl alcohol administered four times daily continuously.

PURPOSE: Previous experience with perillyl alcohol (POH) was with a formulation of 500-mg capsules each containing 250 mg POH and soybean oil. This formulation resulted in the ingestion of large amounts of soybean oil (>10 g/day). Dose-limiting toxicities (DLT) were primarily gastrointestinal. Prior studies also showed no further increase in POH metabolite concentrations with doses of >1600 mg/m2. Therefore, a new formulation of POH was developed (700 mg containing 675 mg POH) in an effort to improve dose and metabolite concentrations delivered and toxicity encountered with chronic dosing. EXPERIMENTAL DESIGN: Eligible patients had refractory solid malignancies. Dose escalation occurred in cohorts of three at the dose levels/dose of 1350 mg, 2025 mg, 2700 mg, 3375 mg and 4050 mg, administered orally four times a day in a 28-day cycle. RESULTS: A group of 19 patients were enrolled. One DLT occurred at dose level 5. This cohort was expanded to six patients, and no further DLT occurred. The maximum tolerated dose was not reached. The predominant toxicity was gastrointestinal. Nausea and vomiting occurred in 63% of patients (12/19, grade 1 in 10). The same proportion of patients (12/19) experienced heartburn and indigestion, primarily grade 1. Although the side effects were mild in nature, three patients withdrew from treatment, citing intolerable gastrointestinal toxicity. The AUCs of POH metabolites did not appear to increase from level 1 to level 2 or change significantly from day 1 to day 29. Inter- and intrapatient variability in metabolite levels was observed. CONCLUSIONS: This reformulation of POH appears to be an improvement upon the prior formulation, by reducing the number of capsules ingested and the degree of gastrointestinal toxicity per dose. It does not appear to offer any metabolite pharmacokinetic advantage. A dose of 2050 mg administered four times daily was easily tolerated. Higher doses can be administered but with increasing gastrointestinal toxicity that limits compliance.

Adult↗
PubMed2003

The Consortium to Investigate Vascular Impairment of Cognition: methods and first findings.

BACKGROUND: The Consortium to Investigate Vascular Impairment of Cognition (CIVIC) is a Canadian, multi-centre, clinic-based prospective cohort study of patients with Vascular Cognitive Impairment (VCI). We report its organization and the impact of diagnostic criteria on the study of VCI. METHODS: Nine memory disability clinics enrolled patients and recorded their usual investigations and care. A case report form included all vascular dementia (VaD) individual criteria for each of four sets (National Institute of Neurological Disorders and Stroke (NINDS-AIREN), Alzheimer's Disease Diagnostic Treatment Centers (ADDTC), the ICD-10 Classification of Mental and Behavioural Disorders (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score (HIS). Investigators, having completed the case report form, were asked to make a clinical judgement about the cognitive diagnosis based on the best available information, including neuroimaging. RESULTS: Of 1,347 patients (mean age 72 years; 56% women), 846 (63%) were diagnosed with dementia and 324 (24%) were diagnosed with VCI. The proportion of patients diagnosed with VaD by the diagnostic criteria was: 23.9% (n = 322) by DSM-IV, 10.2% (n = 137) by HIS, 4.3% (n = 58) by ICD-10, 3.8% (n = 51) by ADTCC, and 3.6% (n = 48) by NINDS-AIREN. Judged against a clinical diagnosis of VaD, the sensitivity/specificity of each was: DSM-IV (0.77/0.80); HIS (0.41/0.92); ICD-10 (0.29/0.98); ADTCC (0.24/0.98); NINDS-AIREN (0.42/0.995). Compared with a clinical diagnosis of VCI, sensitivities were lower for the diagnostic criteria, reflecting the exclusion of patients who did not have dementia. CONCLUSIONS: Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer's disease. Even for patients who do, the proportion identified with VaD varies widely. Criteria based on empirical analyses need to be developed and validated.

Adult↗
PubMed2002

A case study of pure word deafness: modularity in auditory processing?

AL, a woman with an acquired disturbance of auditory processing beginning in the second decade, was originally diagnosed as having pure word deafness. Recent analysis with a wide range of stimuli suggests that her comprehension deficit also extends to a subset of musical and non-verbal environmental sounds. The perceptual demands of the different auditory stimuli appear to account for part of the apparent material specificity. Additionally, over the years, the presumed temporal lobe cortical pathology has been supplemented by a mild to moderate, peripheral low-frequency hearing loss and evidence of dysfunction in lower level auditory processing pathways. The current peripheral dysfunction closely resembles cases recently labeled as auditory neuropathy. The diagnosis of pure word deafness should not be based on a limited set of auditory stimuli; additionally, a careful assessment using modern audiological techniques should be performed to evaluate peripheral auditory functions.

Achievement↗