Brian R. Ott

Memantine treatment in mild to moderate Alzheimer disease: a 24-week randomized, controlled trial.

OBJECTIVE The objective of this study was to compare the efficacy and safety of the moderate-affinity, uncompetitive N-methyl-d-aspartate receptor antagonist, memantine, versus placebo in patients with mild to moderate Alzheimer disease (AD). METHOD This was a randomized, double-blind, placebo-controlled clinical trial conducted at 42 U.S. sites. Participants were 403 outpatients with mild to moderate AD and Mini-Mental State Examination scores of 10-22 randomized to memantine (20 mg/day; N=201) or placebo (N=202) for 24 weeks. Primary outcomes were change from baseline at 24 weeks on the Alzheimers Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a measure of cognition, and on the Clinicians Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), a global measure. Secondary outcomes included change on the Neuropsychiatric Inventory (NPI) and the Alzheimers Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL(23)), measures of behavior and function, respectively. RESULTS Most (82.4%) participants completed the trial. Memantine resulted in significantly better outcomes than placebo on measures of cognition, global status, and behavior when based on the protocol-specified primary last observation carried forward imputation as well as a mixed-models repeated-measures approach applied to the continuous outcomes. Treatment discontinuations because of adverse events for memantine versus placebo were 19 (9.5%) and 10 (5.0%), respectively. CONCLUSIONS These results support the safety and efficacy of memantine for the treatment of mild to moderate AD.

Acute quadriplegic myopathy: A complication of treatment with steroids, nondepolarizing blocking agents, or both

We studied two patients who were given high-dose intravenous steroid therapy and were intubated for status asthmaticus. Both became quadriplegic and wasted within 2 weeks. EMG had myopathic abnormalities. Muscle biopsy revealed severe atrophy of most muscle fibers, with disorganization of myofibrils and selective loss of thick (myosin) filaments. Immunohistologic stains for myosin isoforms confirmed the decrease or absence of this protein. Both patients clinically improved over several months.

A longitudinal study of drivers with Alzheimer disease

Objective: The goal of this study was to define the natural progression of driving impairment in persons who initially have very mild to mild dementia. Methods: We studied 128 older drivers, including 84 with early Alzheimer disease (AD) and 44 age-matched control subjects without cognitive impairment. Subjects underwent repeated assessments of their cognitive, neurologic, visual, and physical function over 3 years. Self-reports of driving accidents and traffic violations were supplemented by reports from family informants and state records. Within 2 weeks of the office evaluation, subjects were examined by a professional driving instructor on a standardized road test. Results: At baseline, subjects with AD had experienced more accidents and performed more poorly on the road test, compared to controls. Over time, both groups declined in driving performance on the road test, with subjects with AD declining more than controls. Survival analysis indicated that while the majority of subjects with AD passed the examination at baseline, greater severity of dementia, increased age, and lower education were associated with higher rates of failure and marginal performance. Conclusions: This study confirms previous reports of potentially hazardous driving in persons with early Alzheimer disease, but also indicates that some individuals with very mild dementia can continue to drive safely for extended periods of time. Regular follow-up assessments, however, are warranted in those individuals.

Quality of Life measures for dementia

Over the past 10 years, several instruments developed specifically for the assessment of Quality of Life (QOL) in dementia have been introduced. The goal of the current review is to present, compare, and critique existing QOL measures for dementia populations to assist investigators and clinicians in selecting the optimal inventory for their specific needs. Nine measures are reviewed with a focus on conceptualizations of QOL, psychometric data, targeted patient population, and administration and scoring procedures. Critical discussion and comparison of the instruments is presented after the scales are described individually. Differences in definitions of QOL, assessment procedures, and methods that were used to establish the validity of instruments are highlighted. An important direction for future research on QOL scales for dementia is to establish their responsiveness to change over time. It will also be important to identify factors that affect reports of QOL, determine the how perceived QOL affects decisions regarding the care of dementia patients, and evaluate interventions to increase patient QOL.

Apathy and Executive Dysfunction in Mild Cognitive Impairment and Alzheimer Disease

OBJECTIVE The authors assessed and contrasted frontally mediated behavior changes in patients diagnosed with Mild Cognitive Impairment (MCI) and Alzheimer disease (AD). Apathy, executive dysfunction, and disinhibition are common in AD, but these behaviors have not been studied in MCI. METHODS Participants were patients diagnosed with AD (n=25) or MCI (n=20). Current behavior and behavior before the onset of cognitive impairment was rated by knowledgeable informants on the Frontal Systems Behavior Scale (FrSBe). RESULTS Apathy and executive dysfunction exhibited the greatest increase in both MCI and AD, and both increased significantly over baseline scores. No significant differences in behavior change were found between the two groups. Behavior change was moderately correlated with a measure of dementia severity, indicating that greater disease severity was associated with more abnormal behavior. CONCLUSION Changes in frontally-mediated behaviors are common in very early and mild stages of cognitive impairment, even before functional decline in daily living is evident. These behaviors deserve more study in MCI because they may have implications for prognosis, treatment adherence, family distress, and patient quality of life.

Neuropsychological deficits associated with driving performance in Parkinson's and Alzheimer's disease

Neuropsychological and motor deficits in Parkinsons disease that may contribute to driving impairment were examined in a cohort study comparing patients with Parkinsons disease (PD) to patients with Alzheimers disease (AD) and to healthy elderly controls. Nondemented individuals with Parkinsons disease [Hoehn & Yahr (H&Y) stage I-III], patients with Alzheimers disease [Clinical Demetia Rating scale (CDR) range 0-1], and elderly controls, who were actively driving, completed a neuropsychological battery and a standardized road test administered by a professional driving instructor. On-road driving ability was rated on number of driving errors and a global rating of safe, marginal, or unsafe. Overall, Alzheimers patients were more impaired drivers than Parkinsons patients. Parkinsons patients distinguished themselves from other drivers by a head-turning deficiency. Drivers with neuropsychological impairment were more likely to be unsafe drivers in both disease groups compared to controls. Compared to controls, unsafe drivers with Alzheimers disease were impaired across all neuropsychological measures except finger tapping. Driving performance in Parkinsons patients was related to disease severity (H&Y), neuropsychological measures [Rey Osterreith Complex Figure (ROCF), Trails B, Hopkins Verbal List Learning Test (HVLT)-delay], and specific motor symptoms (axial rigidity, postural instability), but not to the Unified Parkinson Disease Rating Scale (UPDRS) motor score. Multifactorial measures (ROCF, Trails B) were useful in distinguishing safe from unsafe drivers in both patient groups.

Driving and Dementia: A Review of the Literature

The purpose of this article is to review the literature on the ability of individuals with dementia to drive an automobile. Based on a review of the literature, several factors were identified that may be useful in differentiating between people with dementia who presently remain safe drivers from those who have progressed to impaired driving. These factors include disease duration and severity, sex, patient self-assessment, family assessment, neuropsychological measures, findings on road evaluations, and driving simulator testing. The approach of the physician to driving and dementia is addressed, including in-office screening, referral for on-road driving assessments, and the potential for physician reporting to state agencies.

Gender Differences in the Behavioral Manifestations of Alzheimer's Disease

OBJECTIVE: To examine the relationship between gender and specific types of behavior problems that occur in patients with Alzheimers disease.

Prediction of on-road driving performance in patients with early Alzheimer's disease.

Objectives: Physicians and family members frequently are asked to provide information about driving ability in patients with Alzheimers disease (AD), yet there has been little research on the validity of their assessments of driving performance.

Exacerbation of parkinsonism by tacrine.

A patient with Alzheimers disease and mild features of parkinsonism was treated with tacrine. Tremor and gait dysfunction worsened but responded to the addition of levodopa without adversely affecting cognitive function. The implications for experimental treatment strategies of patients with combined Alzheimers and Parkinsons disease are discussed.