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Biomedical subjects

Morris Freedman

Publications and source records attributed to Morris Freedman.

15 recordsLinked to original sources

Bilingualism as a protection against the onset of symptoms of dementia.

This study examined the effect of lifelong bilingualism on maintaining cognitive functioning and delaying the onset of symptoms of dementia in old age. The sample was selected from the records of 228 patients referred to a Memory Clinic with cognitive complaints. The final sample consisted of 184 patients diagnosed with dementia, 51% of whom were bilingual. The bilinguals showed symptoms of dementia 4 years later than monolinguals, all other measures being equivalent. Additionally, the rate of decline in Mini-Mental State Examination (MMSE) scores over the 4 years subsequent to the diagnosis was the same for a subset of patients in the two groups, suggesting a shift in onset age with no change in rate of progression.

Age of Onset↗

Utility-based Quality of Life measures in Alzheimer's disease.

OBJECTIVES: To explore whether Alzheimer's disease patients could rate their quality of life (QOL) using utility-based health indexes, and to provide new knowledge about the measurement properties of these instruments for patient and caregiver proxy ratings. METHODS: A convenience sample of 60 mild-moderate AD patients and their caregivers were randomized to complete the Quality of Well-Being Scale (QWB), Health Utilities Index (HUI3) or EQ-5D and visual analogue scale (VAS) on two occasions. Test-retest reliability (intraclass correlation coefficients) and convergent validity (Spearman correlations) of utility scores with global health status, activities of daily living, comorbidity, mood, cognition and other utility measures were assessed. RESULTS: Completion time was shortest for the combined EQ-5D and VAS. For patients with mild dementia and for proxies, reliability was >or= 0.70 for the EQ-5D, QWB and HUI3. The EQ-5D had a ceiling effect for patient ratings. Convergent validity was demonstrated for patient and proxy ratings, with the strongest validity for EQ-5D ratings and the weakest validity for HUI3 patient ratings. Mean patient utility scores were significantly higher than mean proxy scores for all measures (p<0.001). CONCLUSIONS: For patient and proxy ratings, the EQ-5D had the best combination of measurement properties, although it had a substantial ceiling effect for patient ratings. Proxy QOL ratings did not accurately reflect patients' ratings.

Activities of Daily Living↗

Progress in clinical neurosciences: Canadian guidelines for the development of antidementia therapies: a conceptual summary.

The magnitude of the problems faced by an aging Canadian society has been clearly identified. Perhaps the single most important problem is the increasing incidence of dementia. Alzheimer's disease (AD) accounts for 50-60% of the dementias in later life within a spectrum of other contributing dementias. Regulatory approval has been given to Acetylcholinesterase inhibitors for the symptomatic treatment of mild to moderate AD, and conditional approval to memantine for the symptoms of moderate to severe AD. There has been no regulatory approval for the treatment of the degenerative dementias beyond AD. The very rapid progress in the past decade in biotechnology and in the molecular biology of the dementias is supporting a new generation of innovative treatment strategies that will more directly target the underlying disease pathogenic mechanisms. Such treatments will foreseeably include immunotherapies, anti-aggregants that may prevent misfolding and deposition of proteins, and neuroregenerative interventions. These Guidelines follow the 2nd Canadian Conference on the Development of Antidementia Therapies, held in 2004, which covered a range of design, methodological and ethical issues facing clinical researchers and regulatory authorities. They are intended to provide a common point of reference and guidance in Canada for therapeutic development of the dementias.

Canada↗

Learning and memory as a function of age in Down syndrome: a study using animal-based tasks.

Individuals with Down syndrome (DS) are at a high risk for developing Alzheimer disease (AD) after the age 40; however, low levels of intellectual functioning, coupled with impaired language ability, confound the detection of AD. Comparative neuropsychological tests developed in animal models of aging and cognition do not require intact language function and can be useful for detecting changes in cognition. Experimental paradigms used to detect age-dependent cognitive deficits in animal models were applied in the present study to measure cognitive function in a group of 20 adults with DS ranging in age from 22 to 58 years. Object discrimination, reversal learning, and spatial and object memory were administered using a modified Wisconsin General Testing Apparatus and reinforcement (penny rewards). When considering age as the only clinical variable to parallel the animal studies, age was significantly correlated with performance on object memory and marginally related to performance on reversal learning and spatial memory. However, when evaluating multiple clinical variables including age, a measure of intellectual ability (FSIQ), scores on the Dementia Questionnaire for Persons with Mental Retardation (DMR), and gender using regression analysis, scores on the DMR were the best predictors of errors of reversal learning, whereas FSIQ was the best predictor of performance on object memory. These results suggest that while age may be related to performance on learning and memory tasks, other clinical variables may be stronger predictors of performance in adults with DS. These changes may reflect prefrontal and medial temporal lobe dysfunction that is associated with the development of AD pathology in DS.

Adult↗

Age-associated cognitive deficits in humans and dogs: a comparative neuropsychological approach.

We compared performance of younger and older human participants to that of younger and older dogs on tasks that evaluate object discrimination, egocentric spatial ability, object recognition, spatial memory, and cognitive flexibility. Our goal was to determine whether (i) tasks sensitive to advanced age in dogs are also age-sensitive in humans; (ii) the pattern of task difficulty observed in dogs mirrors that observed in humans; (iii) dogs and humans use similar strategies to solve equivalent tasks. Dogs performed more poorly than humans on reversal tasks that evaluate cognitive flexibility. We suggest that dogs, most notably older dogs, use different strategies than healthy humans when solving these tasks. Humans appear to test a priori hypotheses to solve the task at hand. As a consequence, expectations about the complexity of the task being tested can impair human performance. By contrast, dogs appear to rely more heavily on either simpler hypotheses, or associative trial and error learning, which probably accounts for their difficulty in learning non-matching tasks. Dogs also show perseverative responding, which hinders the acquisition of reversal tasks.

Adult↗

Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review.

OBJECTIVE: To review the role of oral atypical antipsychotic drugs in the management of the behavioural and psychological symptoms of dementia (BPSD). DATA SOURCES: Medline, Embase, and the Cochrane Library. Reference lists were reviewed and experts were contacted to identify additional trials. STUDY SELECTION: Double blind randomised controlled trials that evaluated the four oral atypical antipsychotic therapies for BPSD. REVIEW METHODS: Two reviewers assessed trial validity independently. DATA EXTRACTION: Demographics of patients, study duration, dose of antipsychotic, primary end points, adverse events. RESULTS: 77 abstracts were reviewed. Five randomised trials (1570 patients) evaluating risperidone and olanzapine were identified. The quality of trials was generally good. Most participants were in an institution (> 96%), elderly (weighted mean 82.3 years), and had Alzheimer's disease (76.3%). Trials lasted 6-12 weeks. Treatment with atypical antipsychotic drugs was superior to placebo for the primary end point in three of the five trials. Two trials comparing risperidone with haloperidol did not find any differences in the primary measures of efficacy. Adverse events were common and included extrapyramidal symptoms, somnolence, and abnormal gait. CONCLUSIONS: Although atypical antipsychotic drugs are being used with increasing frequency, few randomised trials have evaluated their use for BPSD. Limited evidence supports the perception of improved efficacy and adverse event profiles compared with typical antipsychotic drugs.

Administration, Oral↗

The contribution of autobiographical significance to semantic memory: evidence from Alzheimer's disease, semantic dementia, and amnesia.

In a previous study [Memory Cognit., in press], we demonstrated that some semantic concepts are more likely than others to be associated with specific personal memories, and that this autobiographical significance gives these concepts special status in long-term memory. In this paper, we explore the possible neural correlates of autobiographically significant semantic knowledge and examine whether or not autobiographical significance is a factor in determining patterns of semantic memory loss caused by brain damage. Using famous names that were rated on various attributes, including autobiographical significance, by control participants in a norming study [Memory Cognit., in press], we found that semantic dementia (SD) patients were more likely to recognize, identify and remember autobiographically significant episodes involving famous names that were rated high in autobiographical significance as compared to equally familiar names that were rated low. By contrast, people with Alzheimer's disease (AD) and people with medial temporal lobe (MTL) amnesia did not exhibit this preference for names rated high in autobiographical significance. Furthermore, in tests of free recall, recognition, fame judgment and speeded reading, semantic dementia patients demonstrated a performance advantage for autobiographically significant famous names, whereas the other patient groups did not. These findings suggest a critical role for medial temporal regions in the mediation of autobiographical memory and the interaction between personal experience and semantic memory. Theoretical implications are discussed.

Adult↗

Increases in homocysteine are related to worsening of stroop scores in healthy elderly persons: a prospective follow-up study.

BACKGROUND: Elevated blood levels of homocysteine have been associated with cerebrovascular disease and cognitive impairment. The authors' objective was to determine the relationship between cognitive changes and variations in tHcy levels over time in healthy elderly volunteers. METHODS: This prospective cohort study was conducted in healthy community-dwelling older adults without cerebrovascular disease at baseline and followed them for 2.3 years. Cobalamin, red blood cell folate, total serum homocysteine (tHcy), and creatinine levels were measured and recorded. Cognitive measures included the Mini Mental State Examination, California Verbal Learning Test, Mattis Dementia Rating Scale, and Stroop Neuropsychological Inventory. RESULTS: At baseline, participants with elevated tHcy levels had lower Stroop scores (72.7 vs 85.35, p <.05) than did participants with normal tHcy levels. The tHcy levels correlated significantly with Stroop scores at baseline and follow-up. At follow-up, tHcy levels had increased in 104 participants (group I) and decreased in 76 participants (group II). Compared to mean baseline values, the mean tHcy in both groups had changed significantly at follow-up (p <.05 and p <.001, respectively). Participants in group I had significantly lower Stroop scores in multivariate analyses at follow-up than at baseline. The scores of participants in group II at follow-up were not significantly different than their scores at baseline. The rate of change of tHcy levels and the rate of change of the Stroop scores were significantly correlated (r = -0.264, p <.001) after multivariate analysis. Stroop scores decreased by 22% at follow-up in participants whose tHcy levels increased by 40% from baseline to follow-up. CONCLUSION: Elevated tHcy levels and increases in tHcy during a short period of time are associated with decreased Stroop scores in otherwise cognitively normal elderly volunteers.

Aged↗

Metabolic markers of cobalamin deficiency and cognitive function in normal older adults.

OBJECTIVES: To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults. DESIGN: Cross-sectional study. SETTING: Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada. PARTICIPANTS: Two hundred eighty-one cognitively normal, community-dwelling participants aged 65 and older. MEASUREMENTS: Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop). RESULTS: Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (beta=-0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P<.01). Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop scores than subjects with normal tHcy (P<.05). No biochemical parameters were associated with the Mattis Dementia Rating Scale scores. CONCLUSION: This study indicates that, in normal elderly subjects, some cognitive scores are related to serum methylcitric acid and possibly homocysteine.

Aged↗

Is low-dose oral cobalamin enough to normalize cobalamin function in older people?

OBJECTIVES: To investigate whether the use of low-dose oral cobalamin (Cbl) supplements by older persons, as frequently found in multivitamin preparations, affects their Cbl serum concentrations and function, determined by measurements of the serum Cbl-related metabolites methylmalonic acid (MMA), homocysteine (HCYS), and methylcitric acid (MCTR). DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: Two hundred forty-two independent, active, community-living, older adult volunteers recruited from community events and activities for seniors. MEASUREMENTS: We systematically collected data on vitamin supplement intake, diet, medications, and medical and surgical history. Serum was obtained for Cbl, MMA, HCYS, and MCTR, and creatinine and hematological parameters. RESULTS: Serum levels of Cbl were significantly higher in subjects on oral Cbl supplements (2-37.5 microg/day). Similarly, serum levels of the metabolites MMA, HCYS, and MCTR were also lower in subjects on Cbl supplementation. Intake of low-dose oral supplements of Cbl significantly reduced the odds of low Cbl levels or high MMA. The relationship between Cbl supplement dosage and the biochemical parameters was dose dependent. CONCLUSION: Oral Cbl (2-37.5 microg/day) intake by community-dwelling healthy older adults is associated with higher serum levels of Cbl and improved or normalized Cbl function, as indicated by lower concentrations of the metabolites MMA, HCYS, and MCTR. Use of low-dose oral Cbl replacement therapy might be sufficient to prevent Cbl deficiency in a large proportion of this population.

Administration, Oral↗

Is cerebral microembolism in mechanical prosthetic heart valves clinically relevant?

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) are frequently detected by transcranial Doppler (TCD) ultrasound in patients with mechanical prosthetic heart valves (PHVs), but published data about their clinical relevance are controversial. This study was undertaken to determine the clinical relevance of HITS in patients with mechanical PHVs. METHODS: The authors prospectively studied patients with mechanical PHVs using TCD monitoring for microemboli detection with and without O2 inhalation. The cognitive testing of patients included the Mini-Mental State Examination, the Dementia Rating Scale, and MicroCog. RESULTS: The authors studied 36 patients (20 women, aged 58 +/- 13 years). HITS were detected in 72% of patients, with a nonsignificant increase of HITS rate in the aortic valve group (P = .07). There was no significant difference in HITS rate between asymptomatic and symptomatic patients. In a multiple linear regression model, HITS rate was predicted only by younger age (P = .024). No correlation was found between HITS rate and the cognitive performance of patients. There was a significant decrease in HITS rate after 100% O2 inhalation compared to baseline levels (32.8 +/- 40.2 vs 6.1 +/- 11.3, P = .011). Subgroup analysis in asymptomatic patients confirmed this finding (P = .017), but in symptomatic patients, decreased HITS rate was not statistically significant (P = .18). CONCLUSION: Only age was a significant predictor of HITS in patients with mechanical PHVs. The lack of association between HITS, clinical symptoms, and cognitive functioning suggests that most of these signals represent harmless epiphenomena, and only HITS detected after O2 inhalation have any clinical relevance.

Analysis of Variance↗

Potential interactions between herbal medicines and conventional drug therapies used by older adults attending a memory clinic.

OBJECTIVE: Herbal medicines and conventional drug therapies are often taken in combination. The objective of our study was to identify the range of natural health products and conventional drug therapies used by older adults (aged 65 years and over) attending a memory clinic, and to specifically evaluate the frequency of potential interactions between herbal medicines and conventional drug therapies. DESIGN: We interviewed consecutive patients attending the Memory Disorders Clinic at the Baycrest Centre for Geriatric Care, a University of Toronto teaching hospital, between 4 July and 15 August 2000. Patients were asked to bring to their appointment all natural health products (i.e. herbal medicines, vitamins and minerals) and conventional drug therapies (i.e. prescription and over-the-counter) they were currently using. We collected information on current and previously used natural health products and current conventional drug therapies. Patients were classified as having the potential for an interaction if they were using a current herbal medicine in combination with a conventional drug therapy and the interaction had been reported previously in the medical literature. PARTICIPANTS: We interviewed 195 consecutive patients attending the Memory Disorders Clinic at the Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada. RESULTS: Of the 195 patients in our sample, 33 (17%) were 'current users', 19 (10%) were 'past users', and 143 (73%) were 'never users' of herbal medicines. Among the 52 patients who were 'current or past users', the most frequently used herbal medicines were ginkgo (Ginkgo biloba) [39 users], garlic (n = 10), glucosamine sulphate (n = 9) and echinacea (n = 8). Among the 33 patients who were current users, the most commonly used herbal medicines were Ginkgo biloba (n = 22), glucosamine sulphate (n = 8) and garlic (n = 6). Among the 33 current users, we identified 11 potential herb-drug interactions in nine patients. The 11 herb-drug interactions we identified were between ginkgo and aspirin (acetylsalicylic acid) [n = 8], ginkgo and trazodone (n = 1), ginseng and amlodipine (n = 1) and valerian and lorazepam (n = 1). CONCLUSIONS: Herbal medicines are widely used. Almost one-third of current users of herbal medicines were at risk of a herb-drug interaction. The most common potential herb-drug interaction was between ginkgo and aspirin. This finding has important potential implications because both of these products are regularly used by older people. Physicians and other healthcare providers should be aware of potential herb-drug interactions and should monitor and inform their patients accordingly.

Aged↗