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1.
Alzheimers Dement ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958575

ABSTRACT

INTRODUCTION: Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure. METHODS: We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls. RESULTS: Circulating amyloid beta (Aß), tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, p-tauS235, ubiquitin, and lysosomal-associated membrane protein 1-positive EVs distinguished AD samples. p-tau181, p-tau217, p-tauS235, and ubiquitin-positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p-tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p-tauS235. DISCUSSION: This nFC-based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC-based measurements in larger populations and comparison to "gold standard" biomarkers is an exciting next step for developing AD diagnostic tools. HIGHLIGHTS: Extracellular vesicles represent promising biomarkers of Alzheimer's disease (AD) that can be measured in the peripheral circulation. This study demonstrates the utility of nanoscale flow cytometry for the measurement of circulating extracellular vesicles (EVs) in AD blood samples. Multiple markers including amyloid beta, tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, and p-tauS235 accurately distinguished AD samples from healthy controls. Future studies should expand blood and cerebrospinal fluid-based EV biomarker development using nanoflow cytometry approaches.

2.
Age Ageing ; 49(6): 995-1002, 2020 10 23.
Article in English | MEDLINE | ID: mdl-32559288

ABSTRACT

BACKGROUND: concurrent declines in gait speed and cognition have been associated with future dementia. However, the clinical profile of 'dual decliners', those with concomitant decline in both gait speed and cognition, has not been yet described. We aimed to describe the phenotype and the risk for incident dementia of those who present with dual decline in comparison with non-dual decliners. METHODS: prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants' gait speed, cognition, medical status, functionality, incidence of adverse events and dementia, biannually over 7 years. Gait speed was assessed with a 6-m electronic walkway and global cognition using the MoCA test. We compared characteristics between dual decliners and non-dual decliners using t-test, chi-square and hierarchical regression models. We estimated incident dementia using Cox models. RESULTS: among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual decliners had a 3-fold risk (HR: 3.12, 95%CI: 1.23-7.93, P = 0.017) of progression to dementia compared with non-dual decliners. Dual decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (P = 0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual decliners group. Adding hypertension and dyslipidemia increased the explained variation by 8 and 10%, respectively. The risk of becoming a dual decliner was 4-fold higher if hypertension was present. CONCLUSION: older adults with a concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. Older adults with dual decline have a distinct phenotype with a higher prevalence of hypertension, a treatable condition.


Subject(s)
Dementia , Walking Speed , Aged , Cognition , Dementia/diagnosis , Dementia/epidemiology , Female , Gait , Humans , Male , Phenotype , Prospective Studies
4.
J Am Geriatr Soc ; 66(9): 1676-1683, 2018 09.
Article in English | MEDLINE | ID: mdl-29608780

ABSTRACT

OBJECTIVES: To compare the trajectories of motor and cognitive decline in older adults who progress to dementia with the trajectories of those who do not. To evaluate the added value of measuring motor and cognitive decline longitudinally versus cross-sectionally for predicting dementia. DESIGN: Prospective cohort study with 5 years of follow-up. SETTING: Clinic based at a university hospital in London, Ontario, Canada. PARTICIPANTS: Community-dwelling participants aged 65 and older free of dementia at baseline (N=154). MEASUREMENTS: We evaluated trajectories in participants' motor performance using gait velocity and cognitive performance using the MoCA test twice a year for 5 years. We ascertained incident dementia risk using Cox regression models and attributable risk analyses. Analyses were adjusted using a time-dependent covariate. RESULTS: Overall, 14.3% progressed to dementia. The risk of dementia was almost 7 times as great for those whose gait velocity declined (hazard ratio (HR)=6.89, 95% confidence interval (CI)=2.18-21.75, p=.001), more than 3 times as great for those with cognitive decline (HR=3.61, 95% CI=1.28-10.13, p=.01), and almost 8 times as great in those with combined gait velocity and cognitive decline (HR=7.83, 95% CI=2.10-29.24, p=.002), with an attributable risk of 105 per 1,000 person years. Slow gait at baseline alone failed to predict dementia (HR=1.16, 95% CI=0.39-3.46, p=.79). CONCLUSION: Motor decline, assessed according to serial measures of gait velocity, had a higher attributable risk for incident dementia than did cognitive decline. A decline over time of both gait velocity and cognition had the highest attributable risk. A single time-point assessment was not sufficient to detect individuals at high risk of dementia.


Subject(s)
Cognitive Dysfunction/psychology , Dementia/epidemiology , Gait/physiology , Physical Functional Performance , Aged , Aged, 80 and over , Brain/physiopathology , Cognitive Dysfunction/physiopathology , Dementia/etiology , Disease Progression , Female , Follow-Up Studies , Geriatric Assessment , Humans , Incidence , Independent Living , Male , Neuropsychological Tests , Ontario , Proportional Hazards Models , Prospective Studies , Risk Factors
5.
JAMA Neurol ; 74(7): 857-865, 2017 07 01.
Article in English | MEDLINE | ID: mdl-28505243

ABSTRACT

Importance: Gait performance is affected by neurodegeneration in aging and has the potential to be used as a clinical marker for progression from mild cognitive impairment (MCI) to dementia. A dual-task gait test evaluating the cognitive-motor interface may predict dementia progression in older adults with MCI. Objective: To determine whether a dual-task gait test is associated with incident dementia in MCI. Design, Setting, and Participants: The Gait and Brain Study is an ongoing prospective cohort study of community-dwelling older adults that enrolled 112 older adults with MCI. Participants were followed up for 6 years, with biannual visits including neurologic, cognitive, and gait assessments. Data were collected from July 2007 to March 2016. Main Outcomes and Measures: Incident all-cause dementia was the main outcome measure, and single- and dual-task gait velocity and dual-task gait costs were the independent variables. A neuropsychological test battery was used to assess cognition. Gait velocity was recorded under single-task and 3 separate dual-task conditions using an electronic walkway. Dual-task gait cost was defined as the percentage change between single- and dual-task gait velocities: ([single-task gait velocity - dual-task gait velocity]/ single-task gait velocity) × 100. Cox proportional hazard models were used to estimate the association between risk of progression to dementia and the independent variables, adjusted for age, sex, education, comorbidities, and cognition. Results: Among 112 study participants with MCI, mean (SD) age was 76.6 (6.9) years, 55 were women (49.1%), and 27 progressed to dementia (24.1%), with an incidence rate of 121 per 1000 person-years. Slow single-task gait velocity (<0.8 m/second) was not associated with progression to dementia (hazard ratio [HR], 3.41; 95% CI, 0.99-11.71; P = .05)while high dual-task gait cost while counting backward (HR, 3.79; 95% CI, 1.57-9.15; P = .003) and naming animals (HR, 2.41; 95% CI, 1.04-5.59; P = .04) were associated with dementia progression (incidence rate, 155 per 1000 person-years). The models remained robust after adjusting by baseline cognition except for dual-task gait cost when dichotomized. Conclusions and Relevance: Dual-task gait is associated with progression to dementia in patients with MCI. Dual-task gait testing is easy to administer and may be used by clinicians to decide further biomarker testing, preventive strategies, and follow-up planning in patients with MCI. Trial Registration: clinicaltrials.gov: NCT03020381.


Subject(s)
Cognitive Dysfunction/physiopathology , Dementia/physiopathology , Disease Progression , Gait/physiology , Psychomotor Performance/physiology , Aged , Aged, 80 and over , Biomarkers , Female , Follow-Up Studies , Humans , Incidence , Male , Neuropsychological Tests , Risk
6.
Aging Ment Health ; 21(11): 1184-1191, 2017 11.
Article in English | MEDLINE | ID: mdl-27454406

ABSTRACT

OBJECTIVES: Subjective cognitive decline is considered to be a core feature of pre-Alzheimer's disease (AD) conditions, the vast majority of literature having focused on memory concerns. Neuropsychological studies have implicated executive dysfunction on objective performance measures in AD, but no research has evaluated whether individuals with AD have concerns about their executive functions and whether it differs from their caregiver's concerns. In the present study, we sought to evaluate self- and informant ratings of executive functioning in patients with mild AD. METHOD: Participants were 23 patients with mild AD and 32 healthy elderly controls (HC) and their informants who completed the Behavior Rating Inventory of Executive Function - Adult version. RESULTS: Patients with AD and their informants reported greater executive dysfunction than the HC group and their informants, respectively, and patients reported greater difficulty than their informants. The largest effect size for both self- and informant ratings was obtained for the Working Memory scale. CONCLUSIONS: These findings indicate that subjective cognitive concerns in mild AD extend beyond the memory domain to executive functions. That greater difficulty was endorsed by patients than their informants suggests that at least in the mild stage of AD some awareness of executive dysfunction may be maintained in some patients. Implications for clinical care are discussed.


Subject(s)
Alzheimer Disease/physiopathology , Cognitive Dysfunction/physiopathology , Diagnostic Self Evaluation , Executive Function/physiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
7.
J Gerontol A Biol Sci Med Sci ; 71(11): 1476-1482, 2016 11.
Article in English | MEDLINE | ID: mdl-26984391

ABSTRACT

BACKGROUND: Cognitive-frailty, defined as the presence of both frailty and cognitive impairment, is proposed as a distinctive entity that predicts dementia. However, it remains controversial whether frailty alone, cognitive-frailty, or the combination of cognitive impairment and slow gait pose different risks of incident dementia. METHODS: Two hundred and fifty-two older adults free of dementia at baseline (mean age 76.6±8.6 years) were followed up to 5 years with bi-annual visits including medical, cognitive, and gait assessments. Incident all-cause of dementia and cognitive decline were the main outcomes. Frailty was defined using validated phenotypic criteria. Cognition was assessed using the Montreal Cognitive Assessment while gait was assessed using an electronic walkway. Cox Proportional Hazards models were used to estimate the risk of cognitive decline and dementia for frailty, cognitive-frailty, and gait and cognition models. RESULTS: Fifty-three participants experienced cognitive decline and 27 progressed to dementia (incident rate: 73/1,000 person-years). Frailty participants had a higher prevalence of cognitive impairment compared with those without frailty (77% vs. 54%, p = .02) but not significant risk to incident dementia. Cognitive-frailty increased incident rate (80/1,000 person-years) but not risk for progression to dementia. The combination of slow gait and cognitive impairment posed the highest risk for progression to dementia (hazard ratio: 35.9, 95% confidence interval: 4.0-319.2; p = 0.001, incident rate: 130/1,000 person-years). None of the models explored significantly predicted cognitive decline. CONCLUSIONS: Combining a simple motor test, such as gait velocity, with a reliable cognitive test like the Montreal Cognitive Assessment is superior than the cognitive-frailty construct to detect individuals at risk for dementia. Cognitive-frailty may embody two different manifestations, slow gait and low cognition, of a common underlying mechanism.


Subject(s)
Cognitive Dysfunction/epidemiology , Dementia/epidemiology , Frail Elderly , Geriatric Assessment , Aged , Aged, 80 and over , Disease Progression , Female , Health Status Indicators , Humans , Incidence , Male , Neuropsychological Tests , Phenotype , Prevalence , Risk Factors , Walking Speed
8.
J Aging Phys Act ; 24(2): 169-80, 2016 Apr.
Article in English | MEDLINE | ID: mdl-25838271

ABSTRACT

OBJECTIVE: It was hypothesized that a combined Taoist Tai Chi (TTC) and a memory intervention program (MIP) would be superior to a MIP alone in improving everyday memory behaviors in individuals with amnestic mild cognitive impairment (aMCI). A secondary hypothesis was that TTC would improve cognition, self-reported health status, gait, and balance. METHOD: A total of 48 individuals were randomly assigned to take part in MIP + TTC or MIP alone. The TTC intervention consisted of twenty 90 min sessions. Outcome measures were given at baseline, and after 10 and 22 weeks. RESULTS: Both groups significantly increased their memory strategy knowledge and use, ratings of physical health, processing speed, everyday memory, and visual attention. No preferential benefit was found for individuals in the MIP + TTC group on cognition, gait, or balance measures. CONCLUSIONS: Contrary to expectations, TTC exercise did not specifically improve cognition or physical mobility. Explanations for null findings are explored.


Subject(s)
Amnesia/therapy , Cognitive Dysfunction/therapy , Exercise Therapy/methods , Gait , Memory/physiology , Tai Ji/methods , Aged , Aged, 80 and over , Amnesia/psychology , Cognition/physiology , Cognitive Dysfunction/psychology , Exercise , Female , Humans , Male , Neuropsychological Tests , Postural Balance , Treatment Outcome
9.
Can Geriatr J ; 18(3): 159-67, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26495050

ABSTRACT

BACKGROUND: The annual Scientific Meeting of the Canadian Association on Gerontology was held on October 24 and 25, 2008 in London, Ontario. Prior to the annual meeting, mobility and cognition experts met on October 23, 2008 to engage in a pre-conference workshop. METHODS: Discussions during the workshop addressed novel areas of research and knowledge and research gaps pertaining to the interaction between mobility and cognition in seniors. RESULTS: Workshop presenters moved from the neuromuscular, biomechanics, and neurology of gait impairments, and falls through the role of cognition and mood on mobility regulation to the whole person in the environment. Research gaps were identified. CONCLUSIONS: Despite a consensus that mobility and cognition are increasingly correlated as people age, several gaps in our understanding of mechanisms and how to assess the interaction were recognized. The gaps originally identified in 2008 are still pertinent today. Common and standardized assessments for "mobility and cognition" are still not in place in current practice. Interventions that target mobility and cognitive decline as a single entity are still lacking.

10.
J Alzheimers Dis ; 43(1): 193-9, 2015.
Article in English | MEDLINE | ID: mdl-25079803

ABSTRACT

BACKGROUND: Gait deficits are prevalent in people with dementia and increase their fall risk and future disability. Few treatments exist for gait impairment in Alzheimer's disease (AD) but preliminary studies have shown that cognitive enhancers may improve gait in this population. OBJECTIVE: To determine the efficacy of donepezil, a cognitive enhancer that improves cholinergic activity, on gait in older adults newly diagnosed with AD. METHODS: Phase II clinical trial in 43 seniors with mild AD who received donepezil. Participants had not previously received treatment with cognitive enhancers. Primary outcome variables were gait velocity (GV) and stride time variability (STV) under single and dual-task conditions measured using an electronic walkway. Secondary outcomes included attention and executive function. RESULTS: After four months of treatment, participants with mild AD improved their GV from 108.4 ± 18.6 to 113.3 ± 19.5 cm/s, p = 0.010; dual-task GV from 80.6 ± 23.0 to 85.3 ± 22.3 cm/s, p = 0.028. Changes in STV were in the expected direction although not statistically significant. Participants also showed improvements in Trail Making Tests A (p = 0.030), B (p = 0.001), and B-A (p = 0.042). CONCLUSION: Donepezil improved gait in participants with mild AD. The enhancement of dual-task gait suggests the positive changes achieved in executive function as a possible causal mechanism. This study yielded a clinically significant estimate of effect size; as well, the findings are relevant to the feasibility and ethics considerations for the design of a Phase III clinical trial.


Subject(s)
Alzheimer Disease/drug therapy , Anti-Dyskinesia Agents/therapeutic use , Gait Disorders, Neurologic/drug therapy , Gait/drug effects , Indans/therapeutic use , Nootropic Agents/therapeutic use , Piperidines/therapeutic use , Aged , Alzheimer Disease/complications , Alzheimer Disease/physiopathology , Attention/drug effects , Cholinesterase Inhibitors/therapeutic use , Donepezil , Executive Function/drug effects , Female , Gait Disorders, Neurologic/complications , Gait Disorders, Neurologic/physiopathology , Humans , Male , Neuropsychological Tests , Severity of Illness Index , Treatment Outcome
11.
Dement Geriatr Cogn Disord ; 39(1-2): 68-80, 2015.
Article in English | MEDLINE | ID: mdl-25358336

ABSTRACT

AIM: To determine whether 4 months of rivastigmine treatment would result in metabolic changes and whether metabolic changes correlate with changes in cognition in people with Alzheimer's disease (AD). METHODS: Magnetic resonance spectra were acquired from the posterior cingulate cortex of subjects with AD at 3 T. Magnetic resonance imaging scans and cognitive tests were performed before and 4 months after the beginning of the treatment. Metabolite concentrations were quantified and used to calculate the metabolite ratios. RESULTS: On average, the N-acetylaspartate/creatine (NAA/Cr) ratio decreased by 12.7% following 4 months of rivastigmine treatment, but changes in the NAA/Cr ratio correlated positively with changes in Mini-Mental State Examination scores. CONCLUSION: This positive correlation between changes in NAA/Cr and changes in cognitive performance suggests that the NAA/Cr ratio could be an objective indicator of a response to rivastigmine treatment.


Subject(s)
Alzheimer Disease/drug therapy , Aspartic Acid/analogs & derivatives , Cholinesterase Inhibitors/therapeutic use , Cognition Disorders/drug therapy , Creatine/metabolism , Gyrus Cinguli/metabolism , Phenylcarbamates/therapeutic use , Aged , Aged, 80 and over , Alzheimer Disease/metabolism , Aspartic Acid/metabolism , Cognition Disorders/metabolism , Female , Humans , Magnetic Resonance Imaging , Male , Neuropsychological Tests , Rivastigmine
12.
Neurology ; 84(2): 174-81, 2015 Jan 13.
Article in English | MEDLINE | ID: mdl-25503617

ABSTRACT

OBJECTIVE: To determine the safety and tolerability of 3 doses of intranasal oxytocin (Syntocinon; Novartis, Bern, Switzerland) administered to patients with frontotemporal dementia (FTD). METHODS: We conducted a randomized, parallel-group, double-blind, placebo-controlled study using a dose-escalation design to test 3 clinically feasible doses of intranasal oxytocin (24, 48, or 72 IU) administered twice daily for 1 week to 23 patients with behavioral variant FTD or semantic dementia (clinicaltrials.gov registration number NCT01386333). Primary outcome measures were safety and tolerability at each dose. Secondary measures explored efficacy across the combined oxytocin vs placebo groups and examined potential dose-related effects. RESULTS: All 3 doses of intranasal oxytocin were safe and well tolerated. CONCLUSIONS: A multicenter trial is warranted to determine the therapeutic efficacy of long-term intranasal oxytocin for behavioral symptoms in FTD. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with FTD, intranasal oxytocin is not significantly associated with adverse events or significant changes in the overall neuropsychiatric inventory.


Subject(s)
Frontotemporal Dementia/drug therapy , Oxytocin/administration & dosage , Administration, Intranasal , Aged , Aged, 80 and over , Dose-Response Relationship, Drug , Double-Blind Method , Emotions , Empathy , Female , Frontotemporal Dementia/psychology , Humans , Male , Middle Aged , Oxytocin/adverse effects , Treatment Outcome
13.
Can J Occup Ther ; 80(3): 171-80, 2013 Jun.
Article in English | MEDLINE | ID: mdl-24224229

ABSTRACT

BACKGROUND: Enhancing occupational therapy practice requires critical examination of assessment tools and the conclusions being drawn from their use. When working with cognitively impaired older individuals, judgments about occupational competence are often informed by an assessment of cognitive competence. PURPOSE: The Cognitive Competency Test (CCT) is a frequently used measure in Canada to inform predictions of occupational competence. However, there is an absence of published evidence that addresses its validity. METHODS: To appraise validity of the CCT, a retrospective chart review (n = 107) of CCT reports for inpatient and outpatient clients with cognitive impairment was conducted. Data were subjected to exploratory factor analyses to examine the factor structure, and the measure was compared with commonly used clinical variables reflecting cognitive and occupational competence. FINDINGS: Results suggest that the CCT measures a unitary construct and provide some support for its predictive capacity. IMPLICATIONS: CCT scores can add incremental validity to cognitive screens, such as the Mini Mental State Exam, when evaluating occupational competence.


Subject(s)
Cognitive Dysfunction/diagnosis , Neuropsychological Tests , Occupational Therapy/methods , Aged , Aged, 80 and over , Canada , Female , Humans , Male , Neuropsychological Tests/standards , Retrospective Studies
14.
Can J Neurol Sci ; 40(5): 678-83, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23968941

ABSTRACT

OBJECTIVE: The goal of this study was to quantify the impact of the suggested education correction on the sensitivity and specificity of the Montreal Cognitive Assessment (MoCA). METHOD: Twenty-five outpatients with dementia and 39 with amnestic mild cognitive impairment (aMCI) underwent a diagnostic evaluation, which included the MoCA. Thirty-seven healthy controls also completed the MoCA and psychiatric, medical, neurological, functional, and cognitive difficulties were ruled out. RESULTS: For the total MoCA score, unadjusted for education, a cut-off score of 26 yielded the best balance between sensitivity and specificity (80% and 89% respectively) in identifying cognitive impairment (people with either dementia or aMCI, versus controls). When applying the education correction, sensitivity decreased from 80% to 69% for a small specificity increase (89% to 92%). The cut-off score yielding the best balance between sensitivity and specificity for the education adjusted MoCA score fell to 25 (61% and 97%, respectively). CONCLUSIONS: Adjusting the MoCA total score for education had a detrimental effect on sensitivity with only a slight increase in specificity. Clinically, this loss in sensitivity can lead to an increased number of false negatives, as education level does not always correlate to premorbid intellectual function. Clinical judgment about premorbid status should guide interpretation. However, as this effect may be cohort specific, age and education corrected norms and cut-offs should be developed to help guide MoCA interpretation.


Subject(s)
Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Dementia/diagnosis , Dementia/psychology , Educational Status , Neuropsychological Tests , Aged , Aged, 80 and over , Dermatitis, Contact , Female , Humans , Male , Mental Status Schedule , ROC Curve , Retrospective Studies
15.
Can J Occup Ther ; 80(2): 71-81, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23926759

ABSTRACT

BACKGROUND: Within the area of dementia care, occupational therapists are asked to predict occupational competence in everyday living and often do so by assessing cognitive competence. Considering the cognitive changes that occur with dementia over time, the construct of cognitive competence is a key consideration. Still, a gap exists in the literature examining the relationship between cognitive competence and occupational competence. PURPOSE: This study developed a consensus among participating Canadian occupational therapists regarding the components of cognitive competence they considered essential to predict occupational competence in people with dementia. METHOD: A three-round Delphi study was completed with English- and French-speaking occupational therapists (n = 127; 116; 125) experienced in dementia care. FINDINGS: Ten cognitive components were identified as essential to predict occupational competence in individuals with dementia. IMPLICATIONS: The 10 identified components provide direction for assessment practices and education in dementia care and for development of measurement tools.


Subject(s)
Cognition Disorders/diagnosis , Cognition Disorders/rehabilitation , Dementia/rehabilitation , Occupational Therapy/methods , Awareness , Cognition Disorders/complications , Communication , Delphi Technique , Dementia/complications , Humans , Learning
16.
Brain ; 136(Pt 3): 859-71, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23436505

ABSTRACT

Gait disorders are common in the course of dementia, even at the stage of mild cognitive impairment, owing to probable changes in higher levels of motor control. Since motor control message is ultimately supported in the brain by the primary motor cortex and since cortical lesions are frequent in the dementia process, we hypothesized that impairments of the primary motor cortex may explain the early gait disorders observed in mild cognitive impairment. Our purpose was to determine whether the neurochemistry of the primary motor cortex measured with proton magnetic resonance spectroscopy, and its volume, were associated with gait performance while single and dual-tasking in mild cognitive impairment. Twenty community dwellers with mild cognitive impairment, aged 76 years (11) [median (interquartile range)] (30% female) from the 'Gait and Brain Study' were included in this analysis. Gait velocity and stride time variability were measured while single (i.e. walking alone) and dual tasking (i.e. walking while counting backwards by seven) using an electronic walkway (GAITRite System). Ratios of N-acetyl aspartate to creatine and choline to creatine and cortical volume were calculated in the primary motor cortex. Participants were categorized according to median N-acetyl aspartate to creatine and choline to creatine ratios. Age, gender, body mass index, cognition, education level and subcortical vascular burden were used as potential confounders. Participants with low N-acetyl aspartate to creatine (n = 10) had higher (worse) stride time variability while dual tasking than those with high N-acetyl aspartate to creatine (P = 0.007). Those with high choline to creatine had slower (worse) gait velocity while single (P = 0.015) and dual tasking (P = 0.002). Low N-acetyl aspartate to creatine was associated with increased stride time variability while dual tasking (adjusted ß = 5.51, P = 0.031). High choline to creatine was associated with slower gait velocity while single (adjusted ß = -26.56, P = 0.009) and dual tasking (adjusted ß = -41.92, P = 0.022). Cortical volume correlated with faster gait velocity while single (P = 0.029) and dual tasking (P = 0.037), and with decreased stride time variability while single tasking (P = 0.034). Finally, the probability of exhibiting abnormal metabolite ratios in the primary motor cortex was 63% higher among participants with major gait disturbances in dual task. Those with compromised gait velocity in dual task had a 2.05-fold greater risk of having a smaller cortical volume. In conclusion, the neurochemistry and volume of the primary motor cortex were associated with gait performance while single and dual tasking. Stride time variability was mainly sensitive to neuronal function (N-acetyl aspartate to creatine), whereas gait velocity was more affected by inflammatory damage (choline to creatine) and volumetric changes. These findings may contribute to a better understanding of the higher risks of mobility decline and falls in subjects with mild cognitive impairment.


Subject(s)
Cognitive Dysfunction/metabolism , Gait Disorders, Neurologic/metabolism , Gait/physiology , Motor Cortex/metabolism , Aged , Cognitive Dysfunction/complications , Cognitive Dysfunction/physiopathology , Female , Gait Disorders, Neurologic/etiology , Gait Disorders, Neurologic/physiopathology , Humans , Magnetic Resonance Spectroscopy , Male , Motor Cortex/pathology , Motor Cortex/physiopathology
18.
Gait Posture ; 35(1): 96-100, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21940172

ABSTRACT

Gait impairment is a prominent falls risk factor and a prevalent feature among older adults with cognitive impairment. However, there is a lack of comparative studies on gait performance and fall risk covering the continuum from normal cognition through mild cognitive impairment (MCI) to Alzheimer's disease (AD). We evaluated gait performance and the response to dual-task challenges in older adults with AD, MCI and normal cognition without a history of falls. We hypothesized that, in older people without history of falls, gait performance will deteriorate across the cognitive spectrum with changes being more evident under dual-tasking. Gait was assessed using an electronic walkway under single and three dual-tasks conditions. Gait velocity and stride time variability were not significantly different between the three groups under the single-task condition. By contrast, significant differences of decreasing velocity (p<0.0001), increasing stride time (p=0.0057) and increasing stride time variability (p=0.0037) were found under dual-task testing for people with MCI and AD. Less automatic and more complex dual-task tests, such as naming animals and serial subtraction by sevens from 100, created the greatest deterioration of gait performance. Gait changes under dual-tasking for the MCI and AD groups were statistically different from the cognitively normal controls. Dual-task assessment exposed gait impairments not obvious under a single-task test condition and may facilitate falls risk identification in cognitively impaired persons without a history of falls.


Subject(s)
Alzheimer Disease/physiopathology , Cognitive Dysfunction/physiopathology , Gait/physiology , Psychomotor Performance , Accidental Falls , Aged , Alzheimer Disease/psychology , Cognitive Dysfunction/psychology , Humans
19.
Prog Neuropsychopharmacol Biol Psychiatry ; 34(1): 104-10, 2010 Feb 01.
Article in English | MEDLINE | ID: mdl-19833161

ABSTRACT

Galantamine is a cholinesterase inhibitor and allosteric potentiating ligand modulating presynaptic nicotinic acetylcholine receptors that is used in the treatment of Alzheimer disease (AD). The purpose of this study was to determine if galantamine treatment would result in detectable hippocampal metabolite changes that correlated with changes in cognition, as measured by the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog). Short echo-time proton magnetic resonance (MR) spectra were acquired from within the right hippocampus of ten patients using a 4 Tesla magnetic resonance imaging (MRI) scanner. Spectra were used to quantify absolute metabolite levels for N-acetylaspartate (NAA), glutamate (Glu), choline (Cho), creatine (Cr), and myo-inositol (mI). Patient scans and cognitive tests were performed before and 4 months after beginning galantamine treatment, which consisted of an 8 mg daily dose for the first month and a 16 mg daily dose for the remaining three months. The levels of Glu, Glu/Cr, and Glu/NAA increased after four months of treatment, while there were no changes in MMSE or ADAS-cog scores. Additionally, changes (Delta) in Glu over the four months (DeltaGlu) correlated with DeltaNAA, and Delta(Glu/Cr) correlated with DeltaMMSE scores. Increased Glu and the ratio of Glu to Cr measured by MR spectroscopy after galantamine treatment were associated with increased cognitive performance. The increase in Glu may be related to the action of galantamine as an allosteric potentiating ligand for presynaptic nicotinic acetylcholine receptors, which increases glutamatergic neurotransmission.


Subject(s)
Alzheimer Disease/pathology , Cholinesterase Inhibitors/pharmacology , Galantamine/pharmacology , Glutamic Acid/metabolism , Hippocampus/drug effects , Aged , Aged, 80 and over , Alzheimer Disease/drug therapy , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Brain Mapping , Choline/metabolism , Cholinesterase Inhibitors/therapeutic use , Creatine/metabolism , Female , Galantamine/therapeutic use , Humans , Inositol/metabolism , Magnetic Resonance Spectroscopy/methods , Male , Mental Status Schedule , Neuropsychological Tests , Regression Analysis
20.
Can J Occup Ther ; 76(4): 294-8, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19891299

ABSTRACT

BACKGROUND: The National Rehabilitation Reporting System (NRS) is a minimum data set for inpatient rehabilitation units. The system was designed to support administrative decision making from the facility to the national level. PURPOSE: To conduct a pilot study to explore current and potential clinician uses of NRS data, particularly for hip-fractured clients. METHODS: Focus groups with rehabilitation teams from two urban academic geriatric rehabilitation units in Ontario. FINDINGS: Few current uses were identified; barriers to use included timeliness of data reports and perceived lack of sensitivity to clinically significant changes in functional status. Strategies for resolving these barriers were identified, including customization of data reports. IMPLICATIONS: Clinicians will need to work collaboratively with managers, information technology specialists, and software vendors to explore opportunities to maximize potential usefulness of NRS data.


Subject(s)
Databases, Factual , Geriatric Assessment , Hip Fractures/rehabilitation , Outcome Assessment, Health Care/methods , Rehabilitation Centers , Aged , Canada , Disability Evaluation , Humans , Pilot Projects
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