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Dementia screening measures serve an important role in epidemiological research, clinical trials, identifying patients for more comprehensive assessment, and monitoring progression. Telephone-administered measures allow increased flexibility. Although there are several extant telephone-administered measures that offer the promise of efficient detection of cognitive impairment, research evidence supporting their use is limited. We review telephone-based cognitive screening instruments for detecting dementia or mild cognitive impairment, critically review the evidence for their validity, and make recommendations for future research directions. Most measures reviewed do a good job of classifying patients as likely to have dementia or likely to be neurologically healthy. However, with sensitivity values ranging from 38% to 100% and specificity values ranging from 79% to 100%, there is considerable variability in the measures available. Future validation studies should reflect the populations most likely to benefit from a telephone-based measure, namely community-dwelling elderly who have not yet been identified as being cognitively impaired.

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.

This study examined the ability of computerized maze test performance to predict the road test performance of cognitively impaired and normal older drivers. The authors examined 133 older drivers, including 65 with probable Alzheimer disease, 23 with possible Alzheimer disease, and 45 control subjects without cognitive impairment. Subjects completed 5 computerized maze tasks employing a touch screen and pointer as well as a battery of standard neuropsychological tests. Parameters measured for mazes included errors, planning time, drawing time, and total time. Within 2 weeks, subjects were examined by a professional driving instructor on a standardized road test modeled after the Washington University Road Test. Road test total score was significantly correlated with total time across the 5 mazes. This maze score was significant for both Alzheimer disease subjects and control subjects. One maze in particular, requiring less than 2 minutes to complete, was highly correlated with driving performance. For the standard neuropsychological tests, highest correlations were seen with Trail Making A (TrailsA) and the Hopkins Verbal Learning Tests Trial 1 (HVLT1). Multiple regression models for road test score using stepwise subtraction of maze and neuropsychological test variables revealed significant independent contributions for total maze time, HVLT1, and TrailsA for the entire group; total maze time and HVLT1 for Alzheimer disease subjects; and TrailsA for normal subjects. As a visual analog of driving, a brief computerized test of maze navigation time compares well to standard neuropsychological tests of psychomotor speed, scanning, attention, and working memory as a predictor of driving performance by persons with early Alzheimer disease and normal elders. Measurement of maze task performance appears to be useful in the assessment of older drivers at risk for hazardous driving.

This study assessed the clinical utility of contrast sensitivity (CS) relative to attention, executive function, and visuospatial abilities for predicting driving safety in participants with Parkinson's disease (PD). Twenty-five, non-demented PD patients completed measures of contrast sensitivity, visuospatial skills, executive functions, and attention. All PD participants also underwent a formal on-road driving evaluation. Of the 25 participants, 11 received a marginal or unsafe rating on the road test. Poorer driving performance was associated with worse performance on measures of CS, visuospatial constructions, set shifting, and attention. While impaired driving was associated with a range of cognitive and visual abilities, only a composite measure of executive functioning and visuospatial abilities, and not CS or attentional skills, predicted driving performance. These findings suggest that neuropsychological tests, which are multifactorial in nature and require visual perception and visual spatial judgments are the most useful screening measures for hazardous driving in PD patients.

Preliminary evidence suggests that quality of life reports from patients diagnosed with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) are as reliable and valid as data provided by caregivers. To date, no studies compared the factor structure of data provided by caregivers and patients. Factor analyses are important to conduct because they are an indicator of validity. This study compared the factor structure of patient and caregiver reports on the Dementia Quality of Life scale (DQoL). Participants (N=67) were patients diagnosed with amnestic MCI or mild AD and their caregivers. Principal axis factor analyses were run separately on patient and caregiver report data. The three-factor solutions for patient and caregiver data were nearly identical. Three factors corresponding to positive affect, negative affect, and aesthetics emerged reliably from analyses. Thus, data from patients demonstrated a factor structure that was highly consistent with caregiver report data and conformed to meaningful psychological constructs.

Background: Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be safe and to have beneficial effects on cognition, function, behavior, and global patient status in patients with Alzheimer's disease (AD) in studies lasting 3-6 months. It is approved in the U.S. and Europe for the treatment of moderate to severe AD and is currently under investigation for mild to moderate AD., Objective: To evaluate the long-term safety of memantine in patients with mild to moderate AD and to investigate the tolerability of once-daily dose administration., Methods: This 28-week study enrolled 314 patients with mild to moderate AD who had completed a 24-week, double-blind, placebo-controlled lead-in clinical trial of memantine in AD. Following an 8-week double-blind dose titration phase (used to assess the tolerability of different dosing regimens), subjects were assigned to continuous open label memantine (10 mg, bi.d.) treatment for 20 weeks. Safety outcome measures included treatment-emergent adverse events (AEs), deaths, vital signs, electrocardiograms, and laboratory parameters., Results: During the 28-week study (Phase A+Phase B), the most common AEs were falls and other injuries (both 10.8%). AEs resulted in treatment discontinuation in 6.7% of patients. Discontinuations due to AEs were similar in the once-daily dosing groups compared to the twice-daily dosing groups. During dose titration, completion rates were greater than 90% for both groups. Conversion to once-daily dosing in patients already receiving twice-daily doses of memantine was also well tolerated., Conclusions: Memantine monotherapy in patients with mild to moderate AD is safe and well tolerated for at least one year. Once-daily dosing during titration and short-term maintenance therapy is safe and well tolerated.

The impact of excessive daytime sleepiness (EDS) on road test performance was examined in patients with Parkinson's disease (PD). Twenty-one patients with PD completed the Epworth Sleepiness Scale (ESS) and an on-road driving test. Five participants had EDS according to their self-report on the ESS. Neither EDS nor PD medications were associated with on-road driving performance. These findings suggest that in this pilot study EDS did not impair PD patients' driving skills on a formal driving evaluation.

Memantine, an N-methyl-D-aspartate receptor antagonist, is approved in the United States and Europe for the treatment of moderate to severe Alzheimer disease (AD) and has also been investigated in patients with mild to moderate AD. To characterize the specific cognitive benefits of memantine in patients with mild to moderate AD, a post hoc analysis was conducted of a 24-week randomized, double-blind, placebo-controlled, clinical trial comparing memantine (10 mg twice daily) to placebo. Cognition was assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score, individual items, and aggregated subscales, using a mixed model repeated measures analysis. As assessed by the ADAS-cog total score, participants in the placebo group demonstrated significantly more cognitive decline from baseline than participants treated with memantine at all visits beginning at week 8. Subjects treated with placebo also declined significantly more than individuals in the memantine group on 5 of 11 ADAS-cog individual items: orientation, language, comprehension, word finding, and recall of test instructions. Out of 3 ADAS-cog aggregated item subscales (language, memory, and praxis), outcomes in 2 (language and memory) favored memantine. Consistent with findings from trials conducted in moderate to severe AD patients, this post hoc analysis of a randomized clinical trial suggests that memantine benefits core aspects of language and some aspects of memory in patients with mild to moderate AD.

Background: A large number of licensed elderly drivers are demented or are likely to become demented. On-road driving tests, a method often used to assess driver competency, are likely anxiety-provoking for elderly individuals. This article examines the relationship between anxiety and driving performance in a mildly demented and elderly control (EC) sample., Methods: Anxiety ratings of fear and tension, as assessed by visual analog scales, of 84 patients clinically diagnosed with mild Alzheimer's disease (AD) (68 safe/marginal and 16 unsafe drivers) were compared with those of 44 age- and education-equated safe/marginal EC participants, both before and after a standardized on-road driving test., Results: Analyses revealed significant positive correlations between AD patients' pre-road test and post-road test tension and post-road test fear ratings and total road test score. Subsequent analyses of variance showed no significant pre-road test differences in fear ratings between the three groups but significantly higher levels of tension among the unsafe AD participants. After adjusting for baseline group differences, unsafe AD drivers experienced stable or higher anxiety levels after road test, whereas both the EC and safe/marginal AD drivers endorsed a significant reduction in anxiety., Discussion: Unlike their safe EC and safe AD driver counterparts, unsafe AD patients reported continued elevated levels of fear and tension after the road test. Given these findings, we suggest that the most appropriate time for driving instructors to counsel patients regarding their driving skills might be directly after the road test.

A. Tales, R. J. Snowden, M. Brown, and G. Wilcock (2006) have questioned the authors' view of a possible interdependence between attentional systems mediating exogenous spatial orienting and phasic alerting as well as the authors' suggestion that phasic alerting deficits in patients with Alzheimer's disease (AD) may be influencing their performance on tests of spatial orienting. Consistent with this possibility, both laboratories have previously demonstrated increased spatial orienting and decreased phasic alerting in patients with AD. In Tales et al.'s current study, however, they have instead suggested that their results provide evidence for functional independence between these attentional systems in AD. In this commentary, the authors address the misinterpretations of their study and evaluate the degree to which Tales et al.'s study addresses the issues that they raise. Given Tales et al.'s difficulty performing analyses on response time data because of variance issues, the presence of a reduced (although not significant) alerting effect in Tales et al.'s AD group (consistent with the authors' previous findings), and a potential floor effect in their measure of alerting, the authors question the validity of Tales et al.'s conclusions and reaffirm their position that not considering interactions among attentional systems can lead to inaccurate characterizations of the mechanisms by which they operate.

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 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), a measure of cognition, and on the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), a global measure. Secondary outcomes included change on the Neuropsychiatric Inventory (NPI) and the Alzheimer's 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.

Neuropsychological and motor deficits in Parkinson's disease that may contribute to driving impairment were examined in a cohort study comparing patients with Parkinson's disease (PD) to patients with Alzheimer's disease (AD) and to healthy elderly controls. Nondemented individuals with Parkinson's disease [Hoehn & Yahr (H&Y) stage I-III], patients with Alzheimer's 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, Alzheimer's patients were more impaired drivers than Parkinson's patients. Parkinson's 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 Alzheimer's disease were impaired across all neuropsychological measures except finger tapping. Driving performance in Parkinson's 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.

Objectives: To determine the validity and reliability of clinician ratings of the driving competence of patients with mild dementia., Design: Observational study of a cross-section of drivers with mild dementia based on chart review by clinicians with varying types of expertise and experience., Setting: Outpatient dementia clinic., Participants: Fifty dementia subjects from a longitudinal study of driving and dementia., Measurements: Each clinician reviewed information from the clinic charts and the first study visit. The clinician then rated the drivers as safe, marginal, or unsafe. A professional driving instructor compared these ratings with total driving scores on a standardized road test and categorical ratings of driving competence. Clinicians also completed a visual analog scale assessment of variables that led to their determinations of driving competence., Results: Accuracy of clinician ratings ranged from 62% to 78% for the instructor's global rating of safe versus marginal or unsafe. In general, there was moderate accuracy and interrater reliability. Accuracy could have been improved in the least-accurate raters by greater attention to dementia duration and severity ratings, as well as less reliance on the history and physical examination. The most accurate predictors were clinicians specially trained in dementia assessment, who were not necessarily the most experienced in their years of clinical experience., Conclusion: Although a clinician may be able to identify many potentially hazardous drivers, accuracy is insufficient to suggest that a clinician's assessment alone is adequate to determine driving competence in those with mild dementia.

Background: Since cholinesterase inhibitors (CEIs) were approved for use in mild to moderate Alzheimer's disease, the therapeutic efficacy of this class of medications has largely centered on demonstration of short-term improvement in cognition and global function. Later evidence suggested that the beneficial effects of CEIs might be sustainable for at least 3 years and that CEIs may have a disease-modifying effect on Alzheimer's disease. These broad-ranging, long-term effects may explain the recent finding that the use of a CEI among nursing home residents with dementia was associated with lower mortality., Objective: The goal of this study was to investigate whether donepezil treatment is associated with reduced mortality in nursing home residents who have dementia., Methods: We performed a retrospective matched cohort study using the Systematic Assessment of Geriatric Drug Use via Epidemiology database, which contains data collected with the Minimum Data Set on a cross section of 915,469 nursing home residents aged > 65 years between 1998 and 2000 in 6 US states. We identified users of donepezil (5 and 10 mg) and an equal number of matched nonusers in the same facility, date of donepezil use, level of cognitive function, and dementia diagnosis. Comparisons of the 2 groups were made for sociodemographic variables, dementia severity, number of medications, and major comorbid illnesses (heart disease, cancer, diabetes mellitus, chronic obstructive pulmonary disease, and malnutrition), as well as survival over the 2-year study period., Results: A total of 5423 users and 5423 nonusers of donepezil were identified. Based on Cox proportional hazards models, donepezil users showed a lower mortality rate than nonusers. The hazard rate ratio was 0.89 (95% CI, 0.83-0.95). After adjusting for the confounding variables, sociodemographic factors, other psychotropic drugs, and comorbid conditions, this survival advantage remained (hazard rate ratio, 0.90; 95% CI, 0.84-0.96)., Conclusions: A relationship was observed between treatment of nursing home residents with donepezil and lower mortality. If the relationship was due to a direct effect of donepezil use, then this observation has implications for the socioeconomic impact of CEI therapy in those with advanced dementia in the nursing home. These implications deserve future investigation.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.

The Driving Scenes test of the new Neuropsychological Assessment Battery (NAB; [Stern, R.A., & White, T. (2003a). Neuropsychological Assessment Battery. Lutz, FL: Psychological Assessment Resources, Inc.]) measures several aspects of visual attention thought to be important for driving ability. The current study examined the relationship between scores on the Driving Scenes test and on-road driving performance on a standardized driving test. Healthy participants performed significantly better on the Driving Scenes test than did very mildly demented participants. A correlation of 0.55 was found between the brief, office-based Driving Scenes test and the 108-point on-road driving score. Furthermore, the Driving Scenes test scores differed significantly across the driving instructor's three global ratings (safe, marginal, and unsafe), and results of a discriminant function analysis indicated that the Driving Scenes test correctly classified 66% of participants into these groups. Thus, the new NAB Driving Scenes test appears to have good ecological validity for real-world driving ability in normal and very mildly demented older adults.

Objectives: Physicians and family members frequently are asked to provide information about driving ability in patients with Alzheimer's disease (AD), yet there has been little research on the validity of their assessments of driving performance., Design: Cross-sectional., Setting: Participants were recruited from the neurology department of a community hospital affiliated with Brown Medical School., Participants: Participants included 75 older adults (17 with mild AD, 33 with very mild AD, and 25 elderly controls)., Measurements: The participant him/herself, an informant, and an experienced neurologist rated each participant's driving ability on a 3-point rating scale (safe, marginal, unsafe). A professional driving instructor also completed a standardized 108-point on-road driving assessment of each participant and then rated driving ability on the 3-point scale. Ratings were compared with the on-road driving score and with each other., Results: Only the neurologist's rating of the participants' driving abilities was significantly related to on-road driving score. When related to the instructor's safety rating, the neurologist's ratings were the most sensitive and specific. Mini-Mental State Examination score was a borderline covariate for the neurologist's rating. Overall, the instructor was the most stringent rater of participant driving ability, followed by the neurologist, the informant, and the participant., Conclusion: An experienced neurologist's assessment of driving competence may be a valid predictor of driving performance of patients with early AD.

Objective: To investigate whether variations within normal ranges of thyroid functioning are related to cognitive and neuropsychiatric functioning in Alzheimer disease (AD)., Background: Mild alterations of thyroid hormone levels, even in the normal range, are associated with changes in mood and cognitive functioning in older, nondemented adults, and lower concentrations of thyroid hormones have been shown to be associated with an increased risk for cognitive decline. Less is known about the relationship between thyroid hormone levels and cognitive and neuropsychiatric dysfunction in AD., Method: Twenty-eight euthyroid patients with AD on donepezil underwent evaluation of thyroid status, including measures of thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and cognitive and neuropsychiatric assessment with the Alzheimer's Disease Assessment Scale, Neuropsychiatric Inventory, and Visual Analog Mood Scales., Results: Correlational analyses indicated statistically significant associations between FT4 concentrations and self-reported feelings of fear and fatigue. Fear and fatigue were negatively correlated with FT4. There were no significant relationships between thyroid hormones and cognition and other depressive and anxiety symptoms., Conclusions: Results of this preliminary study support a relationship between thyroid status and neuropsychiatric symptoms in euthyroid individuals with AD, with lower concentrations of FT4 associated with fear and fatigue.

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.

Hachinski and co-workers have used the term vascular cognitive impairment-no dementia (VaCIND) to represent the earliest stages of cognitive decline associated with vascular changes [Neurology 57 (4) (2001) 714]. However, the neuropsychological profile of vascular CIND remains unclear. Twenty-five healthy elders, 29 individuals at risk for cerebrovascular disease (R-CVD), 18 individuals with VaCIND, and 26 individuals with vascular dementia (VaD) were examined to determine whether patterns of neuropsychological assessment performance can assist in the differentiation of patients at varying levels of risk and severity for cerebrovascular disease and VaD. The R-CVD group performed within normal expectations on most cognitive measures as compared to the elderly control sample and published clinical norms. Relative to elderly controls, the VaCIND group demonstrated significant difficulties on measures of cognitive flexibility, verbal retrieval, and verbal recognition memory, but not on measures of confrontational naming or verbal fluency. The VaD group was impaired on all cognitive measures assessed. The current findings suggest that poor cognitive flexibility and verbal retrieval in the context of preserved function in other domains may characterize the prodromal stage of VaD.

The effects of aging and Alzheimer's disease (AD) on phasic alerting and exogenous spatial orienting were examined within a single precuing task. Phasic alerting decreased with normal aging and was completely eliminated with AD. AD patients also demonstrated an increased spatial orienting effect, attributable to an increased benefit from spatial orienting that was associated with a decreased benefit from nonselective alerting. These results suggest that performance within the precuing paradigm reflects the product of an interaction between nonselective alerting processes and spatially selective orienting processes. The results also highlight the importance of simultaneously assessing alerting and orienting within the same task, because changes attributable to alerting may otherwise be attributed incorrectly to changes in 1 or more processes associated with spatial orienting.

Background: Prior studies on Quality of Life (QOL) in Alzheimer's disease (AD) have rarely included control participants, or participants with very mild levels of cognitive impairment. Furthermore, there is little data to indicate whether or not mildly impaired patients can provide self-report QOL data or if informant reports are needed., Objectives: This study compared QOL ratings from informants and patients with mild AD (n = 26), Mild Cognitive Impairment (MCI, n = 30), and elderly controls (n = 23)., Methods: Participants (aged 60-91 years) were recruited from an outpatient memory disorder clinic. Elderly controls were recruited from the community. Measures about patients were the Dementia Quality of Life scale, the Neuropsychiatric Inventory-Questionnaire, Instrumental of Activities of Daily Living, and Mini-mental State Exam. Informant depression was assessed with the Geriatric Depression Scale., Results: Results indicated that overall patient-informant agreement for MCI (M=0.24), AD (M=0.48), and controls (M=0.49) did not differ significantly. Self-reported QOL did not differ significantly across the 3 groups. For caregiver-reports, QOL in MCI again did not differ from controls but was significantly greater than QOL in AD for 2 of 6 scales, and QOL in controls was greater than AD for 4 of 6 scales. Regression analyses indicated that neuropsychiatric symptoms were the most consistent predictors of QOL., Conclusions: In summary, informant- and self-perceptions of QOL differed substantially. Results suggest that future investigators should carefully consider gathering QOL information from both informants and patients because they provide unique information regarding patient QOL and, to date, neither source of information has been established to be superior., (Copyright 2004 John Wiley & Sons, Ltd.)

Efficient, valid, and economical methods are needed to measure memory in elderly patients who are participants in clinical trials for the prevention or treatment of dementia. Data provided by knowledgeable informants are an ideal means of assessment, but factors that may limit the validity of informant-report data are not known. This study investigated the living status, relationship type, and educational history of informants and determined the impact of these factors on the validity of informant-report data about patients (N = 62) diagnosed with Alzheimer disease or mild cognitive impairment. Validity of informant-reported memory was indicated by the correlation between the reports and patients' performance on a neuropsychological memory test. Results indicated that informants who lived with patients provided more accurate reports of the patients' memory than informants who did not live with the patient. Spouses were more accurate than other relationship types, although relationship type was confounded with living status. Patient education and neuropsychiatric symptoms were not significantly associated with informant accuracy. Results of this study will aid in selecting informants who can provide the most accurate data about memory disorder patients and will aid in the development of protocols for clinical trials for dementia prevention and treatment.

The authors previously reported that subcortical hyperintensity (SH) and whole-brain volume (WBV) each covary with different subscale scores of the Mattis Dementia Rating Scale (MDRS) among vascular dementia (VaD) patients. The present longitudinal analysis examined these relationships for change. The authors found that SH volume increased and WBV decreased significantly over 12 months. At baseline, SH volume accounted for significant variance in MDRS total score and every subscale score, except Memory. WBV was unrelated to any MDRS measure. After 12 months, SH volume was related only to the Construction subscale score, whereas WBV accounted for the majority of variance in Attention and Memory subscale performance. These findings indicate that although SH volume increases with disease progression, the relative impact of SH volume on cognitive status decreases among patients with advanced VaD.

The syndrome of dementia with Lewy bodies (DLB) is characterised by the clinical triad of fluctuating cognitive impairment, recurrent visual hallucinations and spontaneous motor features of Parkinsonism. In an attempt to define DLB as a distinct clinical syndrome separate from Alzheimer's disease (AD) and Parkinson's disease (PD) with dementia, a consensus workshop in 1995 established a new set of diagnostic criteria. Dementia that precedes or accompanies the onset of spontaneous (i.e., not neuroleptic-induced) Parkinsonism is termed DLB. In addition, fluctuations in alertness, cognition and function and visual hallucinations are emphasised and included as core features of DLB. The degree to which an individual patient exhibits cognitive impairment, behavioural problems and Parkinsonian features is variable. Therefore, treatment must be individualised. Although there are no officially approved drugs for DLB, limited experience from clinical trials, as well as past experience with the treatment of AD and PD patients, provide some basis for making drug choices. The cholinergic deficit seen in DLB makes cholinesterase inhibitor drugs the mainstay of treatment for cognitive impairment. This class of drugs has also shown therapeutic benefit in reducing hallucinations and other neuropsychiatric symptoms of the disease. Because of their relatively greater therapeutic window, cholinesterase inhibitors are also used as first-line therapy for the treatment of psychosis in DLB. Patients with DLB are extremely sensitive to the extrapyramidal side effects of neuroleptic medications. Thus, only atypical antipsychotic agents such as quetiapine, should be considered as alternative treatment for psychosis. Anxiety and depression are best treated with selective serotonin re-uptake inhibitors, whereas REM sleep behaviour disorder may be treated with low dose clonazepam. Parkinsonism responds to dopaminergic agents; however, precipitation or aggravation of hallucinosis may occur. Levodopa is preferred over dopamine agonists due to its lower propensity to cause hallucinations and somnolence. As the diagnostic criteria for DLB become more refined and validated by postmortem studies, it is hoped that rigorous, well-designed trials will be performed, aimed at alleviating the primary target symptoms of dementia, psychosis and Parkinsonism.

A battery of standard neuropsychological tests examining various features of executive function, attention, and visual perception was administered to 27 subjects with questionable to mild dementia and compared to a 4-point caregiver rating scale of driving ability. Based on the results of this study, a computerized maze task, employing 10 mazes, was administered to a second sample of 40 normal elders and questionable to moderately demented drivers. Comparison was made to the same caregiver rating scale as well as to crash frequency. In the first study of neuropsychological tests, errors on Porteus Mazes emerged as the only significant predictor of driving ability in a stepwise regression analysis. In the follow-up study employing the computerized mazes, all 10 mazes were significantly related to driving ability ratings. Computerized tests of maze performance offer promise as a screening tool to identify potential driving impairment among cognitively impaired elderly and demented drivers.

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.

Objective: To determine whether demographic data, dementia severity, functional status, whole brain volume (WBV), or subcortical hyperintensity volume (SH) predict subsequent cognitive decline in vascular dementia (VaD)., Background: The identification of variables that accurately predict progressive cognitive decline in dementia has important clinical implications., Methods: A cohort of 30 patients with VaD completed neurologic and neuropsychologic examinations and magnetic resonance imaging of the brain at baseline and again after 12 months. All participants met clinical and research criteria for VaD according to standard guidelines. Change scores were computed for measures of verbal fluency, verbal learning, and visual learning. Potential correlates of cognitive change included age, education, score on the Hachinski scale, WBV, SH, and functional ability., Results: As a group, lower WBV and lower Hachinski score correlated with decline in verbal fluency and visual learning, whereas lower Hachinski score correlated with decline in verbal learning. However, when subdivided by disease type, this pattern held only for individuals with evidence of a cortical stroke at baseline. No clinical variables correlated with cognitive decline among individuals without a cortical infarction., Conclusions: Assessment of cognitive decline in VaD should be guided by dementia subtype, with particular attention directed at severity of cerebral atrophy rather than classic symptoms of infarction.

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.

The efficacy of a memory-training program to improve word-list recall and recognition was evaluated in 34 patients with probable Alzheimer's disease (AD). The patients, who were all taking donepezil throughout the 6-week intervention, were randomly assigned to a cognitive intervention group or a control group. The Control group received didactic presentations but no formal memory training. Patients were assessed on neuropsychological tests before the 6-week training program, immediately after the training, and 8 weeks after completion of the training. Caregivers, who were blind to group assignment, completed activities of daily living (ADLs) and everyday memory questionnaires at all three time-points. No significant main effects of group (training vs. control) or time were observed on any outcome measures, nor were any significant interactions found. In terms of "process" measures during the 6-week training program, the patients demonstrated modest improvement on recall and recognition of test material presented during the training sessions. These results suggest that although modest gains in learning and memory may be evident in AD patients who are taught specific strategies, the benefits do not generalize to other measures of neuropsychological functioning after a brief intervention.

Objectives: This study evaluated two amnestic behavior changes (repetitive questioning and repetitive actions) to determine their utility in screening for early dementia., Design: Patient data were collected through a retrospective chart review. Comparison data from nondemented older people were collected prospectively from acquaintances of clinic patients., Setting: The setting was a hospital-based outpatient memory disorder clinic., Participants: Participants were older individuals with no cognitive impairment (n = 25), undetermined dementia (n = 50), and definite dementia (n = 25). The undetermined cases were followed for at least 1 year to assess for conversion to dementia., Measurements: Amnestic behaviors were assessed using informant-report for all participants. The behaviors were examined for their ability to distinguish between definite dementia cases and noncases. They were further evaluated for the ability to differentiate undetermined cases that eventually converted to definite dementia from cases that did not convert., Results: Results indicated that repetitive behaviors were common in early and more-severe dementia cases. Repetitive behaviors were relatively uncommon in cognitively intact older participants. In analyses of the full study sample, engagement in repetitive behaviors had high sensitivity (0.97) in identifying dementia cases., Conclusions: Assessing repetitive behaviors in patients may be a useful means for family members and primary care physicians to screen for early cognitive impairment. The assessment can help to identify individuals that should be evaluated further for dementia.

The relationship between MRI findings (i.e., subcortical hyperintensities; SH, whole brain volume) and the cognitive dysfunction of vascular dementia (VaD) was examined. Participants included 24 persons that met NINDS-AIREN criteria for VaD (MMSE = 19.9 +/- 4.2) and underwent comprehensive neuropsychological assessment and MRI brain imaging. The volume of subcortical hyperintensities (SH) was strongly associated with executive-psychomotor performance, but not with performance across other cognitive domains or global cognitive functional level. Conversely, WBV was strongly associated with global cognitive functioning and performance across most cognitive domains (memory, language, visual integration), but not with executive-psychomotor functioning. The failure of SH to account for either the global dementia evident in these VaD patients or impairments across most cognitive domains suggests that deep subcortical white matter disease may only indirectly contribute to the global cognitive dysfunction of VaD. That WBV emerged as a stronger correlate of dementia raises further questions regarding the cerebral mechanisms that contribute to the development of VaD.

Objective: To compare the cognitive and behavioral profiles of Alzheimer's disease (AD) and cognitively impaired patients with Parkinson's disease (PD) and to determine the individual measures that best discriminate the two patient groups., Background: Neuropsychologic studies of patients with AD and PD have generated debate over the distinction between "cortical" and "subcortical" dementias, with some studies showing significant differences and others showing little difference in the cognitive profiles of these groups. Studies evaluating behavioral differences between the patient groups have been somewhat more successful in adequately discriminating these syndromes. To address this issue, we examined cognitive and behavioral profiles of patients with AD and cognitively impaired patients with PD on two frequently used assessment instruments., Method: Patients were diagnosed according to published and accepted criteria for AD and PD. Eighteen patients with AD and 18 patients with PD, matched on age and education, were administered the Mattis Dementia Rating Scale and Frontal Systems Behavior Scale (formally Frontal Lobe Personality Scale)., Results: The two groups did not differ on overall Dementia Rating Scale score or total Frontal Systems Behavior Scale score. However, examination of subscale scores revealed that the patients with AD performed significantly worse than the patients with PD on the Memory subscale of the Dementia Rating Scale, and patients with PD were rated as being more apathetic than the patients with AD on the Frontal Systems Behavior Scale. When these two variables were entered into a discriminant function analysis, an overall classification accuracy of 86% was demonstrated, with 89% of the AD group and 83% of the PD group correctly classified., Conclusions: These findings suggest that even though global cognitive dysfunction and behavioral disturbance may appear similar in patients with AD and cognitively impaired patients with PD, specific measures of these functions that are sensitive to the underlying neuropathology of each disease do differ significantly.

The relationship of behavioral disturbance and dementia severity to activities of daily living (ADLs) in vascular dementia (VaD) was examined in baseline data for 29 VaD patients. A series of stepwise regression analyses was conducted to examine the extent to which dementia severity, apathy, disinhibition, and executive dysfunction predict ADLs (total, basic, and instrumental). For total ADLs, apathy accounted for 36% of the variance and dementia severity accounted for an additional 15%. For basic ADLs, apathy accounted for 27% of the variance. Dementia severity, executive dysfunction, and disinhibition were not significantly associated with basic ADLs. For instrumental ADLs, dementia severity accounted for 37% of the variance and apathy accounted for an additional 14%. These findings highlight the importance of apathy as an independent factor associated with functional independence beyond general cognitive abilities.

Quality of life (QOL) in patients diagnosed with dementia is of critical importance. Reliable and valid measurement of patient QOL is essential to evaluate the effectiveness of treatment interventions and to gain a better understanding of the detrimental impact of dementia on patients' lives. In this study, the psychometric properties of a new scale developed to measure QOL, the Cornell-Brown Scale for Quality of Life, were examined. Data were collected from 50 dementia clinic outpatients with a range of cognitive impairment. Scale ratings were based on a brief, joint interview with caregivers and patients. Findings indicated that the scale demonstrated adequate interrater reliability (intraclass r = 0.90) and internal consistency reliability (Cronbach alpha = 0.81). Criterion validity was indicated by a positive correlation between QOL scores and visual analogue positive mood ratings (Spearman rho = 0.63) and a negative correlation between QOL and dementia severity as measured by Clinical Dementia Ratings (Spearman rho = -0.35). Reliability and validity were not adversely affected by patient cognitive impairment. Thus, preliminary data indicate that the Cornell-Brown Scale for Quality of Life is a brief, easily administered, reliable, and valid measure of QOL.

In the present study, we examined the relationships between ratings on the Global Deterioration Scale (GDS) and activities of daily living and cognitive function in 39 individuals with vascular dementia (VaD). The results of the study revealed significant correlations between GDS rating and performance on cognitive tests, including memory and overall cognitive ability. In addition, the GDS was significantly related to ratings of instrumental activities of daily living. Comparisons between patients with VaD with GDS scores between 4 and 6 (n = 21) and patients with scores between 2 and 3 (n = 18) revealed greater cognitive and functional deficits in the group with higher GDS scores. Further, the GDS score accurately classified 87% of the patients with VaD. These findings provide support for the validity of the GDS in general staging of dementia severity of VaD.

Objectives: To investigate the extent to which treatment with tacrine is associated with a reduction in mortality in nursing home residents with dementia., Design: We performed a retrospective cohort study using the Systematic Assessment and Geriatric drug use via Epidemiology database, which contains data collected with the Minimum Data Set on a cross-section of over 400,000 nursing home residents in five U.S. states., Setting: Retrospective data analysis of residents in nursing homes., Participants: We identified 1,449 users of tacrine and 6,119 nonusers matched on facility, date of tacrine use, level of cognitive function, and dementia diagnosis., Measurements: Comparisons of the two groups were made for sociodemographic variables, dementia severity, number of medications, and major comorbid illness (heart disease, cancer, diabetes mellitus, chronic obstructive pulmonary disease, malnutrition), and survival over the 3-year study period., Results: Based on Cox proportional hazards models, tacrine users showed a significantly lower mortality rate than nonusers. The hazard rate ratio was 0.76 (95% CI = 0.70-0.83). After adjusting for the confounding variables of sociodemographic factors, level of function in activities of daily living, cognitive function, number of drugs, and comorbid illnesses, this survival advantage was still significant at 0.85 (95% CI = 0.77-0.93)., Conclusion: Treatment of nursing home residents with tacrine is associated with lower mortality. This observation has implications for the socioeconomic impact of cholinesterase inhibitor therapy in those with advanced dementia and for quality of life issues in the nursing home that deserve future investigation.

Background: The relationship between subcortical hyperintensity (SH) on magnetic resonance imaging (MRI), cortical perfusion on single photon emission computed tomography (SPECT), and cognitive function is not well understood. The authors examined these relationships in individuals with vascular dementia (VaD), paying particular attention to frontal lobe function to determine whether the presence of SH on MRI was associated with frontal hypoperfusion on SPECT, which in turn would be associated with impairments of executive-attention function., Methods: Patients with vascular dementia (n = 26) were assessed on neurocognitive tests and brain MRI and SPECT. SH volume was quantified from the axial T2-weighted fluid attenuated inversion recovery MRI. Total counts of activation across voxels for 12 cortical regions of interest were determined from SPECT. Perfusion ratios of both total cortical and frontal activation relative to cerebellum activation were derived, and regression analyses were performed to determine the relationships between cognitive, MRI, and SPECT indices., Results: SH volume on MRI was significantly associated with frontal lobe perfusion, but not with global cortical perfusion as measured by SPECT. Frontal lobe perfusion did not consistently correlate with performance on measures of executive-attention function, although both total and frontal perfusion ratios were significantly associated with other cognitive functions., Conclusions: These results suggest that a functional "disconnection" between the frontal lobes and subcortical structures does not fully account for the magnitude of global cognitive impairment in VaD. Cortical perfusion as measured by SPECT appears to be associated with cognitive performance, but not specifically executive-attention dysfunction. Additional studies are needed to further examine the relationship between subcortical and cortical function in VaD.

Objective: To determine the relation between subcortical hyperintensities (SHs) visible on magnetic resonance imaging and executive function among patients with vascular dementia., Background: The relation between SHs and executive dysfunction is not well understood, because studies have varied widely in methodology and have produced conflicting results., Method: We examined the relation between SHs (expressed as a percentage of total brain volume, not including ventricular volume) and six tests of executive function in a well-defined group of 24 individuals with vascular dementia. Executive tests were divided in two groups: Attention/Speed and Abstraction/Problem Solving. Bivariate correlations were computed between individual neuropsychological variables and SHs., Results: Results showed significant bivariate correlations between SHs and three of the four tests in the Attention/Speed domain. Subcortical hyperintensities shared virtually no association with performance on tests in the Abstraction/Problem-Solving domain., Conclusions: The finding that SHs are significantly associated with psychomotor slowing and attentional dysfunction is consistent with what is known about the behavioral manifestations of subcortical disease. More detailed investigations of the regional distribution of SHs as well as measures of atrophy, hypoperfusion, and hypometabolism may be necessary to accurately characterize the complex relation between vascular disease and different aspects of executive dysfunction.

Impairment on screening measures such as the Mattis Dementia Rating Scale (MDRS) provides evidence of dementia in patients with cerebrovascular disease. However, the relationships between neuroimaging findings and performance on the MDRS in vascular dementia (VD) have not been determined. In the present study, we examined the relationships between subcortical hyperintensity (SH) volume and whole brain volume (WBV) on the subscales and total score of the MDRS. Results revealed that SH accounted for a significant amount of variance on the Initiation/Perseveration and Construction subscales, whereas WBV accounted for a significant amount of variance on the Memory subscale. The total score on the MDRS was found to be significantly related to WBV but not SH. These results suggest that subcortical damage and brain volume account for different aspects of cognitive decline in VD and that overall cognitive impairment may reflect cortical and subcortical involvement.

Objective: To define the pathophysiologic substrate of gender differences in cognition and behavior in Alzheimer's disease (AD)., Design: Hemispheric regional cerebral blood flow (rCBF) was studied in a consecutive series of dementia patients using single photon emission computed tomography (SPECT)., Participants: Subjects included 300 outpatients who were studied with SPECT as part of a diagnostic evaluation for degenerative dementia or memory disorder., Method: Based on qualitative descriptions by a radiologist, subjects were classified as having unilateral left, unilateral right, bilateral, or no perfusion defects. Semiquantitative analysis of SPECT images was also performed using region of interest radionuclide counts normalized to the cerebellum., Results: Among 174 females and 126 males, unilateral left hemisphere defects were found more commonly in women than men (24% vs 10%; chi 2 = 9.4; P = .009). This observation was most significant for the 103 females and 62 males regarded as having probable AD (26% vs 8%; chi 2 = 9.3; P = .01). In a multiple regression model of clinical variables, shorter duration of disease and female gender were significant independent predictors of the unilateral left hemisphere pattern among those with probable AD. Age, family history, education, handedness, and severity of cognitive impairment were not significant contributors., Conclusions: Women with AD exhibit greater heterogeneity in rCBF than men. Asymmetry in rCBF occurs more often in women. In some cases, this is related to relative preservation of right hemisphere function in women.

Single-photon emission computed tomography (SPECT) was used in this study to examine the neurophysiologic basis of driving impairment in 79 subjects with dementia. Driving impairment, as measured by caregiver ratings, was significantly related to regional reduction of right hemisphere cortical perfusion on SPECT, particularly in the temporo-occipital area. With increased severity of driving impairment, frontal cortical perfusion was also reduced. Clock drawing was more significantly related to driving impairment than the Mini-Mental State Examination (MMSE). Driving impairment in Alzheimer's disease is related to changes in cortical function which vary according to the severity of the disease. Cognitive tests of visuoperceptual and executive functions may be more useful screening tools for identifying those at greatest risk for driving problems than examinations like the MMSE that are weighted toward left-hemisphere-based verbal tasks., (Copyright 2000 S. Karger AG, Basel)

Objective: To determine gender differences in the prevalence, survival rates, and management of noncognitive behavioral problems of patients with Parkinson's disease (PD) in nursing homes (NH)., Methods: We performed an observational study on 24,402 residents with PD using the Systematic Assessment and Geriatric drug use via Epidemiology (SAGE) database collected from the Minimum Data Set on a cross-section of over 400,000 NH residents in five US states. Gender differences in behavior were used to predict differences in pharmacologic and nonpharmacologic therapies using logistic regression. Similar analyses were done to evaluate gender differences in 1-year survival rates among patients with PD with and without behavioral problems., Results: 36% of men and 33% of women exhibited behavioral problems. Wandering, verbal and physical abusiveness, and inappropriate behavior tended to be more common in men, especially among PD residents with severe cognitive impairment. Hallucinations and delusions were equally prevalent between genders and depressive symptoms were more common in women. Regardless of behavioral manifestation, men were more likely to receive antipsychotic drugs, whereas women were more likely to receive antidepressants. This gender difference in treatment was also widest among the severely demented group. Although women lived longer, no difference in survival curves were noted between PD residents with and without behavioral problems., Conclusion: Gender appears to play an important role in determining the frequency and treatment of behavioral problems of NH residents with PD.

Objective: To define gender differences in noncognitive behavioral problems of patients with AD and differences in the associated treatment of those problems., Design/methods: We performed an observational study using the Systematic Assessment and Geriatric drug use via Epidemiology (SAGE) database, which contains data collected with the Minimum Data Set on a cross-section of nursing home residents in five US states. Behavior problems were documented at the first assessment of 28,367 residents with AD. We evaluated the role of gender differences in behavior as predictors of differences in nonpharmacologic versus specific pharmacologic therapies with psychoactive medications using logistic regression., Results: Men were more likely than women to exhibit behavior problems such as wandering, abusiveness, and social impropriety (59% versus 50% for any behavior problem). Hallucinations and delusions as well as depression were equally prevalent in men and women. Nevertheless, men were more likely to receive psychoactive medications. Among the specific drug categories examined, and controlling for age and degree of cognitive impairment, men were more likely to receive antipsychotic drugs and less likely to be receiving antidepressants., Conclusion: Gender appears to play an important role in determining the frequency of behavioral problems in nursing home residents with AD, which may influence choice of treatments as well as the decision whether to treat. The use of more potent tranquilizers in men with problem behaviors has potential implications for morbidity, deserving further investigation.

In the present study we examined cognitive function, radiographic features, and functional ability in individuals with vascular dementia (VaD). Subjects were subdivided into individuals with only white matter involvement (WM) and individuals with evidence of a cortical infarction in addition to white matter ischemic change (C+WM). Results revealed that both groups of subjects were impaired across cognitive functions. Cognitive performance was more severely impaired among the C+WM group, but the general pattern of deficits did not differ between the two groups. Hachinski scores were significantly higher and instrumental activities of daily living were more severely affected in the C+WM group compared to the WM group. No significant differences were evident between the two groups on overall dementia severity or the extent of white matter involvement. These findings indicate that cognitive function in VaD may be globally impaired, and that cortical infarction in addition to white matter ischemia results in greater impairment, but the differences are largely quantitative rather than qualitative.

Clinically relevant differences in cognition and behavior exist between men and women with Alzheimer's disease. Underlying these differences are variations in the topographic brain changes caused by pathologic processes, as well as differences in hormonal brain physiology and genetic influences. Our understanding of how these gender differences affect the clinical expression of Alzheimer's disease is in its infancy. Research in this area will likely yield further insights into potential therapies directed toward symptomatic and preventive interventions.

The recent successes of large, multicenter clinical trials of acetylcholinesterase inhibitors for symptomatic treatment of Alzheimer's disease have spawned enthusiasm that this common and fatal neurologic disease is "treatable." A parallel explosion has occurred in the consumption of alternative medicines by the public seeking more effective, natural, or safer methods for treatment of dementia. Some of these medicines may, in fact, be biologically active in modulating the disease as well as producing side effects and interactions with accepted pharmaceuticals. This review brings to focus the scientific evidence presently available regarding such agents.