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Summary: Objective: To define the association between late‐onset epilepsy (LOE) and 25‐year change in cognitive performance. Methods: The Atherosclerosis Risk in Communities (ARIC) study is a multicenter longitudinal cohort study with participants from four U.S. communities. From linked Medicare claims, we identified cases of LOE, defined as ≥2 seizure‐related diagnostic codes starting at age ≥67. The ARIC cohort underwent evaluation with in‐person visits at intervals of 3‐15 years. Cognition was evaluated 4 times over >25 years (including before the onset of seizures) using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT); a global z‐score was also calculated. We compared the longitudinal cognitive changes of participants with and without LOE, adjusting for demographics and LOE risk factors. Results: From 8033 ARIC participants with midlife cognitive testing and Medicare claims data available (4523 [56%] female, 1392 [17%] Black), we identified 585 cases of LOE. The rate of cognitive decline was increased on all measures in the participants who developed LOE compared to those without LOE. On the measure of global cognition, participants with LOE declined by −0.43 z‐score points more over 25 years than did participants without epilepsy (95% confidence interval [CI] −0.59 to −0.27). Prior to the onset of seizures, cognitive decline was more rapid on the DWRT, DSST, and global z‐scores in those who would later develop LOE than it was in non‐LOE participants. Results were similar after excluding data from participants with dementia. Significance: Global cognition, verbal memory, executive function, and word fluency declined faster over time in persons developing LOE than without LOE. Declines in cognition preceding LOE suggest these are linked; it will be important to investigate causes for midlife cognitive declines associated with LOE. [ABSTRACT FROM AUTHOR]

Background: In 1983, Huntington's disease (HD) was the first genetic disease mapped using DNA polymorphisms. Shortly thereafter, presymptomatic genetic testing for HD began in the context of two research studies. One of these trials was at the Johns Hopkins University Huntington's Disease Center. Methods: As part of the protocol, risk perception (RP) values were collected at 16 time points before and after testing. The current study investigated changes in RP scores before and after genetic testing. Of the 186 participants with pre‐ and post‐testing RP values, 39 also had contemporaneous research clinic notes and recent semi‐structured interviews available for analysis. Results: The data reveal tremendous diversity in RP. While the RP scores of most individuals change in the way one would expect, 27% of participants demonstrated unexpected changes in RP after disclosure. A significantly higher proportion of individuals who received an expanded repeat result had unexpected changes in RP, compared with those who received normal repeat results. Conclusions: The data suggest that individuals' RP is influenced by more than merely the results of genetic testing. This finding is important for genetic counselors and healthcare providers, as it suggests that even comprehensive patient education and disclosure of genetic test results may not ensure that people fully appreciate their disease risk. This study investigated changes in risk perception (RP) before and after presymptomatic testing for Huntington's disease. RP values were collected at 16 time points over 11 years, and data reveal many participants demonstrate unexpected changes in RP after disclosure of genetic test results. [ABSTRACT FROM AUTHOR]

Resting-state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting-state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting-state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting-state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting-state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting-state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI. [ABSTRACT FROM AUTHOR]

Objective To examine the effects of caregiver and patient characteristics on caregivers' medical care use and cost. Methods One hundred forty-seven caregiver/patient dyads were followed annually for 6 years in three academic Alzheimer's disease centers in the United States. Logistic, negative binomial, and generalized linear mixed models were used to examine overall effects of caregiver/patient characteristics on caregivers' hospitalizations, doctor visits, outpatient tests and procedures, and prescription and over-the-counter medications. Results Patients' comorbid conditions and dependence were associated with increased health-care use and costs of caregivers. Increases in caregiver depressive symptoms are associated with increases in multiple domains of caregivers' health-care use and costs. Discussion Findings suggest expanding our focus on dementia patients to include family caregivers to obtain a fuller picture of effects of caregiving. Primary care providers should integrate caregivers' needs in health-care planning and delivery. Clinical interventions that treat patients and caregivers as a whole will likely achieve the greatest beneficial effects. [ABSTRACT FROM AUTHOR]

The extent to which social cognitive changes reflect a discrete constellation of symptoms dissociable from general cognitive changes in Alzheimer's disease (AD) is unclear. Moreover, whether social cognitive symptoms contribute to disease severity and progression is unknown. The current multicenter study investigated cross-sectional and longitudinal associations between social cognition measured with six items from the Blessed Dementia Rating Scale, general cognition, and dependence in 517 participants with probable AD. Participants were monitored every 6 months for 5.5 years. Results from multivariate latent growth curve models adjusted for sex, age, education, depression, and recruitment site revealed that social cognition and general cognition were unrelated cross-sectionally and throughout time. However, baseline levels of each were related independently to dependence, and change values of each were related independently to change in dependence. These findings highlight the separability of social and general cognition in AD. Results underscore the relevance of considering social cognition when modeling disease and estimating clinical outcomes related to patient disability. [ABSTRACT FROM AUTHOR]

ABSTRACT The clinical syndrome of Huntington's disease (HD) is notable for a triad of motor, cognitive, and emotional features. All HD patients eventually become occupationally disabled; however, the factors that render HD patients unable to maintain employment have not been extensively studied. This review begins by discussing the clinical triad of HD, highlighting the distinction in the motor disorder between involuntary movements, such as chorea, and voluntary movement impairment, with the latter contributing more to functional disability. Cognitive disorder clearly contributes to disability, though the relative contribution compared to motor is difficult to unravel, especially because many of the tests used to asses 'cognition' have a strong motor component. The role of emotional changes in disability needs more study. The literature on contributions to functional disability, driving impairment, and nursing home placement is reviewed. Relevant experience is presented from the long-standing JHU HD observational study on motor versus cognitive onset, as well as on cognitive and motor features at the time when individuals discontinued working. Finally, we briefly review government policies in several countries on disability determination. We interpret the data from our own studies and from the literature to indicate that there is usually a close relationship between cognitive and motor dysfunction, and that it is critical to take both into consideration in determining disability. © 2014 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time. Methods: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores ≥ 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score ≤ 10) and functional (Blessed Dementia Rating Scale score ≥ 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval. Results: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points. Conclusions: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects. [Copyright &y& Elsevier]

Huntington's disease (HD) is a neurodegenerative disorder characterized by early cognitive decline that progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aimed to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high-field-strength magnetic resonance spectroscopy (MRS) at 7 Tesla. Twelve individuals with the HD mutation in premanifest or early-stage disease versus 12 healthy controls underwent 1H magnetic resonance spectroscopy (7.2 mL voxel in the posterior cingulate cortex) at 7 Tesla, and also T1-weighted structural magnetic resonance imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning. Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (−9.6%, P = .02) and glutamate (−10.1%, P = .02) levels than did controls. In contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate ( r2 = 0.50, P = .01) and glutamate (NAA) ( r2 = 0.64, P = .002) in HD subjects. Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in the early stages of HD. N-acetylaspartate and glutamate magnetic resonance spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor. © 2012 Movement Disorder Society [ABSTRACT FROM AUTHOR]

BACKGROUND: Pesticide application is common in agriculture and often results in applied pesticides entering adjacent aquatic systems. This study seasonally analyzed a suite of 17 current- and past-use pesticides in both drainage waters and sediments to evaluate the prevalence of pesticides in drainage ditches across the Lower Mississippi Alluvial Valley (LMAV). RESULTS: There were significantly higher concentrations ( P < 0.05) of current-use than past-use pesticides; however, there were consistently high numbers of detections of past-use pesticides in sediments. Sediment pesticide concentrations were an order of magnitude higher (150-1035 µg kg−1) than water samples (6-20.9 µg L−1). Overall, 87% of all samples analyzed for current- and past-use pesticides were non-detects. p, p′-DDT was detected in 47.5% of all drainage waters and sediments sampled. There were significant correlations (0.372 ≥ r2≤0.935) between detected current-use water and sediment concentrations, but no significant correlations between past-use water and sediment concentrations. CONCLUSION: Overall, there was a high percentage (87%) of sediment and water samples that did not contain detectable concentrations above the lower limit of analytical detection for each respective pesticide. This lack of pesticide prevalence highlights the improved conditions in aquatic systems adjacent to agriculture and a potential decrease in toxicity associated with pesticides in agricultural landscapes in the LMAV. Copyright © 2011 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background: Despite much research on methods to improve new learning and memory in old age, there is virtually no literature on the improvement of autobiographical memory (AM). The present study assessed the effectiveness of a structured autobiographical writing workshop for improving AM, mood and self-concept in older adults. Methods: Fifty-one nondemented older adults (67–96 years) participated. AM was assessed with the Autobiographical Memory Interview (AMI) and the Remote Memory Word Association Task (RMWAT). After completing baseline (BL) testing, participants were randomized to a structured autobiographical writing workshop, a reminiscence group (active control condition) or a no-treatment control group. Follow-up testing was completed at 8 and 34 weeks after BL. Results: Repeated measures ANOVAs failed to reveal a group-by-time interaction for any of the autobiographical memory (AM) measures. Across groups, there was a decrease in number of midand late-life events reported (on the AMI), and memories tended to be less detailed (on the RMWAT) although more pleasant memories were reported with repeated testing. Mood remained unchanged; ratings of self-concept improved across all groups. Conclusions: This is the first study of its kind to use a randomized group design to test an intervention for AM in older adults. In general, our specific intervention was ineffective for increasing recall from one’s life story, mood or self-concept. Methodological limitations and suggestions for future investigation are discussed. [ABSTRACT FROM AUTHOR]

Summary The Personality Assessment Inventory (PAI) is a widely used self-report questionnaire designed to detect and quantify dimensions of adult psychopathology. Previous studies that examined the ability of the PAI to differentiate between patients with psychogenic nonepileptic seizures (PNES) and those with epilepsy (EPIL) have yielded inconsistent results. We compared the full PAI profiles of 62 patients with PNES, 55 with EPIL, and 45 normal control (NC) participants to determine the diagnostic accuracy of the PAI. We also sought to highlight psychopathologic symptoms that may inform psychological treatment of patients with PNES or epilepsy. PNES and EPIL patients reported more somatic concerns and symptoms of anxiety and depression than did NC persons. PNES patients reported more unusual somatic symptoms, as well as greater physical symptoms of anxiety and depression than did patients with EPIL. Classification accuracy of the 'NES Indicator' was not much better than chance, whereas the Conversion subscale alone had reasonable sensitivity (74%) and specificity (67%). Overall, the PAI demonstrated only moderate classification accuracy in an epilepsy monitoring unit sample. However, the inventory appears to identify specific psychopathological symptoms that may be targets of psychological/psychiatric intervention. [ABSTRACT FROM AUTHOR]

Abstract: Background: Epidemiologic evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) delay onset of Alzheimer’s dementia (AD), but randomized trials show no benefit from NSAIDs in patients with symptomatic AD. The Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) randomized 2528 elderly persons to naproxen or celecoxib versus placebo for 2 years (standard deviation = 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID-assigned groups. Methods: We continued the double-masked ADAPT protocol for 2 additional years to investigate incidence of AD (primary outcome). We then collected cerebrospinal fluid (CSF) from 117 volunteer participants to assess their ratio of CSF tau to Aβ1-42. Results: Including 40 new events observed during follow-up of 2071 randomized individuals (92% of participants at treatment cessation), there were 72 AD cases. Overall, NSAID-related harm was no longer evident, but secondary analyses showed that increased risk remained notable in the first 2.5 years of observations, especially in 54 persons enrolled with cognitive impairment––no dementia (CIND). These same analyses showed later reduction in AD incidence among asymptomatic enrollees who were given naproxen. CSF biomarker assays suggested that the latter result reflected reduced Alzheimer-type neurodegeneration. Conclusions: These data suggest a revision of the original ADAPT hypothesis that NSAIDs reduce AD risk, as follows: NSAIDs have an adverse effect in later stages of AD pathogenesis, whereas asymptomatic individuals treated with conventional NSAIDs such as naproxen experience reduced AD incidence, but only after 2 to 3 years. Thus, treatment effects differ at various stages of disease. This hypothesis is consistent with data from both trials and epidemiological studies. [Copyright &y& Elsevier]

Cognitive impairment is common in Parkinson's disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen for dementia and mild cognitive impairment in clinical trials of PD where cognition is not the primary outcome. This Task Force conducted a systematic literature search for cognitive assessments previously used in a PD population. Scales were then evaluated for their appropriateness to screen for cognitive deficits in clinical trials, including brief administration time (<15 minutes), assessment of the major cognitive domains, and potential to detect subtle cognitive impairment in PD. Five scales of global cognition met the predetermined screening criteria and were considered for review. Based on the Task Force's evaluation criteria the Montreal Cognitive Assessment (MoCA), appeared to be the most suitable measure. This Task Force recommends consideration of the MoCA as a minimum cognitive screening measure in clinical trials of PD where cognitive performance is not the primary outcome measure. The MoCA still requires further study of its diagnostic utility in PD populations but appears to be the most appropriate measure among the currently available brief cognitive assessments. Widespread adoption of a single instrument such as the MoCA in clinical trials can improve comparability between research studies on PD. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Objective Although the number of elderly residents living in assisted living (AL) facilities is rising, few studies have examined the AL physical environment and its impact on resident well-being. We sought to quantify the relationship of AL physical environment with resident outcomes including neuropsychiatric symptoms (NPS), quality of life (QOL), and fall risk, and to compare the effects for demented and non-demented residents. Methods Prospective cohort study of a stratified random sample of 326 AL residents living in 21 AL facilities. Measures included the Therapeutic Environmental Screening Scale for Nursing Homes and Residential Care (TESS-NH/RC) to rate facilities and in-person assessment of residents for diagnosis (and assessment of treatment) of dementia, ratings on standardized clinical, cognitive, and QOL measures. Regression models compared environmental measures with outcomes. TESS-NH/RC is modified into a scale for rating the AL physical environment AL-EQS. Results The AL Environmental Quality Score (AL-EQS) was strongly negatively associated with Neuropsychiatric Inventory (NPI) total score (p < 0.001), positively associated with Alzheimer Disease Related Quality of Life (ADRQL) score (p = 0.010), and negatively correlated with fall risk (p = 0.042). Factor analysis revealed an excellent two-factor solution, Dignity and Sensory. Both were strongly associated with NPI and associated with ADRQL. Conclusion The physical environment of AL facilities likely affects NPS and QOL in AL residents, and the effect may be stronger for residents without dementia than for residents with dementia. Environmental manipulations that increase resident privacy, as well as implementing call buttons and telephones, may improve resident well-being. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Elderly persons with mild cognitive impairment (MCI) are at increased risk of dementia and functional impairments. The present study investigated the contribution of three domains of executive cognition to everyday functioning among persons with MCI. Methods 124 MCI patients and 68 cognitively normal elderly participants were administered a cognitive screening battery. These tests were used to divide patients into four subgroups (amnestic single domain, amnestic multiple domain, non-amnestic single domain, and non-amnestic multiple domain). Subjects were then administered 18 executive function tests that assess planning/problem-solving, working memory, and judgment. Performance of everyday activities and everyday cognition was rated with two informant-reported measures. Results All MCI subtypes had more difficulties in everyday activities than cognitively normal elderly participants. Multiple domain MCI patients had more functional impairments than single domain MCI patients. Contrary to our expectations, only one executive function component, working memory, contributed significantly to functional status after controlling for demographic, health-related and other cognitive factors. Conclusions Functional abilities are compromised in all MCI subtypes. Working memory may be associated with functional impairments, but general cognitive measures account for more unique variance. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To estimate incremental effects of patients' dependence and function on costs of care during the early stages of Alzheimer's disease (AD) and to compare strengths of their relationships with different cost components. DESIGN: Multicenter, cross-sectional, observational study. SETTING: Three university hospitals in the United States. PARTICIPANTS: One hundred seventy-nine community-living patients with probable AD, with modified Mini-Mental State Examination scores of 30 or higher. MEASUREMENTS: Patients' dependence was measured using the Dependence Scale (DS). Functional capacity was measured using the Blessed Dementia Rating Scale (BDRS). Total cost was measured by summing direct medical costs and informal costs. Direct medical costs included costs of hospitalization, outpatient treatment and procedures, assistive devices, and medications. Informal costs were estimated from time spent helping with basic and instrumental activities of daily living for up to three caregivers per patient using national average hourly earnings as wage rate. RESULTS: DS and BDRS were associated with higher total cost; a 1-point increase in DS was associated with a $1,832 increase in total cost, and a 1-point increase in BDRS was associated with a $3,333 increase. Examining component costs separately identified potential differences between DS and BDRS. A 1-point increase in BDRS was associated with a $1,406 increase in direct medical cost. A 1-point increase in DS was associated with a $1,690 increase in informal cost. CONCLUSION: Patients' dependence and function related differently to direct medical and informal cost, suggesting that measures of function and dependence provided unique information for explaining variations in cost of care for patients with AD, highlighting the value in measuring both constructs. [ABSTRACT FROM AUTHOR]

Abstract: Background: The objective of this study was to compare total costs of care and its major components for community-living patients with Alzheimer''s disease (AD) or dementia with Lewy bodies (DLB). This cross-sectional analysis of baseline data from the Predictors II Study took place in three university-based AD centers in the U.S. Methods: Community-living patients clinically diagnosed with probable AD (n = 170) or DLB (n = 25) with a modified Mini-Mental State examination (mMMS) score ≥30, equivalent to a score of approximately ≥16 on the Folstein Mini-Mental State Examination (MMSE), participated in this study. Patient and informant reported on patients'' use of direct medical care, direct nonmedical care, and informal care. Patients'' clinical and demographic characteristics included global cognitive status (measured by MMSE), functional capacity (measured by Blessed Dementia Rating Scale), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, age, and sex. Costs were compared by using covariate matching methods. Results: Unadjusted total costs and direct medical costs were not significantly different between AD and DLB patients. Compared with AD patients, unadjusted indirect costs were significantly higher and unadjusted direct nonmedical costs were significantly lower among DLB patients. After adjusting for age, sex, cognitive and functional status, differences in all cost components between DLB and AD patients were no longer statistically significant. Conclusions: Apparent cost differences were largely attributed to differences in patients'' cognitive and functional status. However, the small sample size for DLB patients might have limited power to detect statistically significant differences in costs of care between these groups. [Copyright &y& Elsevier]

Objectives Given recent evidence that activity participation may reduce functional decline, the effect of activity on resident ability to remain in assisted living (AL) is of interest. This study examines the relationship between participation in activities and the length of time residents remain in AL. Methods The data reported here were gathered in the initial phase of the Maryland Assisted Living Study (MDAL), an epidemiologic study of psychiatric disorders in AL. A stratified, random sample of 198 residents of 22 AL facilities in central Maryland was evaluated using a number of cognitive, behavioral, general health, and functional assessments. The total amount of time each resident spent in group and solitary activity in the prior month was quantified. The dependent variable, time to discharge (TTD), was the number of days between the date of initial assessment by the study team and the date of death in AL, discharge, or administrative censoring. Results Greater levels of activity participation at baseline are associated with longer TTD in an univariate Cox proportional hazards model. After adjustment for global cognitive functioning, general medical health, and mobility, greater activity participation remained associated with longer TTD in AL (p = 0.017). Conclusions Higher levels of activity are associated with longer retention in the AL setting. This effect appeared to be independent of other potentially confounding factors such as general health, cognitive impairment, and mobility. This finding is consistent with the hypothesis that engagement in activities delays functional decline, but further longitudinal research is needed to understand this finding. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives To describe patterns of Acetylcholinesterase inhibitor (ACI) use in an Assisted Living (AL) population, and the association of ACIs with retention in AL. Methods As part of the Maryland Assisted Living Study (MD–AL), 198 residents of 22 ALs were evaluated. Dementia was diagnosed in 134, and specifically Alzheimer's disease (AD) in 79, by an expert consensus panel. Data was collected on ACI agent and dose. Vital status and location were recorded every 6 months. Other data included age, duration of residence, general medical health rating (GHMR), Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia (CSDD) and number of non-psychiatric medications. Results The overall ACI treatment rate was 31%. 34.5% of participants with mild to moderate AD were taking ACIs. Only two in seven participants taking rivastigmine were taking an adequate dose. Participants with AD on ACI's did not differ significantly from those not on ACI's in any of the secondary measures except age and duration of residence, those on the agents being somewhat younger and more recently admitted. For participants with AD, only ACI use was significantly associated with retention in AL at 6 months, with a relative risk of death or discharge to higher level care of 0.217. Baseline MMSE was associated with retention for those with non-AD dementia. In a survival analysis ACI use was associated with 228.75 days longer retention in participants with AD. Conclusion ACIs have low rates of use in AL and are associated with better retention for residents with AD. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To estimate the frequency and correlates of insomnia and daytime sleepiness among people with dementia in AL facilities. Methods Participants were randomly selected from 22 different assisted living facilities in Maryland. A total of 124 dementia participants were included in the analysis. All participants were rated on an 11-item sleep questionnaire regarding insomnia and daytime sleepiness. Results Sleep disturbance was present in 59.2% of people with dementia. Of the total sample, 21.8% had insomnia only (IN); 21.6% had excessive daytime sleepiness only (DS); and 16.8% had both IN and DS. 40.8% had no sleep disturbance. IN and DS scores were not significantly associated with each other (r = 0.07, p = 0.43). Of those in the IN group, the majority had mild and moderate dementia and of those in the DS only group the majority had severe dementia. Those with IN only performed the best and DS only performed the worst on both cognitive measures (the Mini Mental State Examination) (F = 3.26, p = 0.014), and on physical measures (the physical subscale of the psychogeraitric dependency rating scale) (F = 6.09, p < 0.001). There was no significant difference between the groups on the Cornell scale for depression in dementia. Conclusion The frequency of insomnia and daytime sleepiness in dementia subjects in AL is similar to that found in nursing homes. Daytime sleepiness is associated with poorer cognitive and day-to-day functioning. Effective management of DS may lead to improved functioning in the AL residents. Insomnia is associated with the best outcomes, even better than those with no sleep disturbance. This finding needs to be replicated. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To estimate the association between dementia and time to discharge from individual assisted living (AL) facilities and examine, in residents with dementia, factors associated with shorter duration of residence in individual AL facilities. DESIGN: Prospective cohort study. SETTING: Twenty-two AL facilities in central Maryland. PARTICIPANTS: Stratified random sample of 198 AL residents followed for a median of 18 months. MEASUREMENTS: Detailed assessments to diagnose dementia; assess treatment of dementia; and rate clinical; cognitive, functional, and quality-of-life measures. RESULTS: Residents with dementia remained in a facility 209 fewer days at the median ( P=.001) than residents without dementia. After adjustment for other variables, lack of treatment for dementia ( P=.01) and more-serious medical comorbidity ( P=.02) were associated with earlier discharge in participants with dementia. Impaired mobility and limited activity participation had weaker associations with earlier time to discharge. CONCLUSION: Dementia may accelerate time to discharge, and its treatment may attenuate this effect. The hypothesis that the detection and treatment of dementia might delay discharge from AL should be tested in randomized trials. [ABSTRACT FROM AUTHOR]

Objectives To compare the demographic, clinical, and psychiatric characteristics of residents living in small (≤15 beds) and large assisted living (AL) facilities in the United States. Methods One hundred and ninety-eight residents in 10 large and 12 small assisted living facilities were comprehensively assessed as part of the Maryland Assisted Living Study (MD-AL). The presence or absence of dementia and psychiatric disturbances and the facilities' recognition and management of these disorders were compared across the two types of AL. Aspects of care delivery were also compared. Results Small facilities had a higher prevalence of dementia (81%) compared to larger facilities (63%) and the mean Mini-Mental State Examination (MMSE) across all residents in small facilities (mean 13.04) was than in large facilities (mean 19.93)(p = 0.000). Almost all (98%) of the residents of small homes carried a diagnosis of a dementia or other psychiatric diagnosis, compared to 74% of residents in large facilities (p < 0.001). Psychosis in particular was more prevalent in the smaller homes and the mean Neuropsychiatric Inventory score, a measure of neuropsychiatric symptoms, was higher compared to large homes. Falls were more common in larger homes despite a greater number of personal care hours per week. The use of safety devices and restraints was significantly less common in large facilities compared to smaller homes, where ‘geri-chair’ and bedrails were more often used. Conclusions Rates of dementia and psychiatric disorder differ in assisted living facilities depending on size of facility. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Most estimates of the cost of informal caregiving in patients with Alzheimer's disease (AD) remain cross-sectional. Longitudinal estimates of informal caregiving hours and costs are less frequent and are from assessments covering only short periods of time. The objectives of this study were to estimate long-term trajectories of the use and cost of informal caregiving for patients with AD and the effects of patient characteristics on the use and cost of informal caregiving. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States (n=170). Generalized linear mixed models were used to estimate the effects of patient characteristics on use and cost of informal caregiving. Patients' clinical characteristics included cognitive status (Mini-Mental State Examination), functional capacity (Blessed Dementia Rating Scale (BDRS)), comorbidities, psychotic symptoms, behavioral problems, depressive symptoms, and extrapyramidal signs. Results show that rates of informal care use and caregiving hours (and costs) increased substantially over time but were related differently to patients' characteristics. Use of informal care was significantly associated with worse cognition, worse function, and higher comorbidities. Conditional on receiving informal care, informal caregiving hours (and costs) were mainly associated with worse function. Each additional point on the BDRS increased informal caregiving costs 5.4%. Average annual informal cost was estimated at $25,381 per patient, increasing from $20,589 at baseline to $43,030 in Year 4. [ABSTRACT FROM AUTHOR]

Objectives Validation of an Italian version of the Telephone Interview for Cognitive Status (I-TICS). Methods Telephone administration of the I-TICS within 6 weeks of face-to-face testing with the Mini Mental State Examination (MMSE), in Probable Alzheimer's disease (AD) patients and healthy controls. Two hundred and seven consecutive outpatients with cognitive impairment were recruited from Dementia Clinic of University Campus BioMedico. Of these, 45 probable AD patients with complete data were analyzed. Other dementias, Mild Cognitive Impairment (MCI), and patients with incomplete data were excluded. The control sample consisted of 64 age- and sex-matched healthy subjects. For diagnosis, an extensive clinical evaluation, laboratory testing, brain imaging, EEG, neuropsychological battery and a depression scale were used. For I-TICS validation, telephone I-TICS and face-to-face MMSE were administered. Results The I-TICS correlated highly and linearly with the MMSE (Pearson's r = 0.904). Conversion equations are provided. Sensitivity and specificity were similar between tests (area under curve = 0.894 for the I-TICS; 0.966 for the MMSE). I-TICS sensitivity was 84% and specificity 86% at a cut-off score of 28. No significant difference in accuracy with the MMSE was present. Total agreement between I-TICS and MMSE was ‘substantial’ at 86% (Cohen's K = 0.717). Repeated testing in a subset of patients showed a disease progression related decrease of 4.2 points/year (t = 2.664; p = 0.018) in I-TICS scores. Conclusion The I-TICS is a valid instrument in clinical and research screening and monitoring of AD. Potential applications in other dementias and MCI are worth further studies. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To examine the natural course of depressive symptoms in patients with probable Alzheimer's disease (AD), specifically, the temporal relationship between depressive symptoms, function, and cognitive status. Design: Multicenter cohort study with follow-up of up to 14 years. Setting: Patients from the two Multicenter Study of Predictors of Disease Course in Alzheimer's Disease (Predictors Study) cohorts were recruited at five sites in the United States and Europe. Participants: Patients diagnosed with probable AD (n=536) enrolled in a longitudinal study (Predictors Study). Measurements: Depressive symptoms were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. The Modified Mini-Mental State (3MS) and Blessed Dementia Rating Scale (BDRS) were used to assess cognitive status and functional activity, respectively. Results: The prevalence of depressive symptoms was stable over the first 3 years of follow-up, at approximately 40%. There was a significant drop to 28% and 24% in the fourth and fifth years of follow-up, respectively. Time-dependent Cox analysis revealed that functional activity (BDRS) but not cognitive status (3MS) was a significant predictor of the first episode of depressive symptoms during follow-up. Generalized estimating equation analyses showed that AD duration and functional activity but not cognitive status were significantly related to depressive symptoms over the entire follow-up period. Conclusion: Depressive symptoms are common in AD, but their prevalence decreases over time. Examination of the temporal relationship between depressive symptoms and risk factors suggests that decline in function but not in cognition precedes the first episode of depressive symptoms in patients with probable AD. [ABSTRACT FROM AUTHOR]

IntroductionA majority of the elderly suffer from some sort of sleep disturbance. Common sleep disturbances are insomnia and excessive daytime sleepiness. There are no published studies on the prevalence of sleep disturbance in the assisted living (AL) setting. ObjectiveTo estimate the prevalence, types, and associations of sleep disturbance in a stratified random sample of AL residents, and to explore the effect of sleep disturbance on cognitive and physical functioning, as assessed by the Mini- Mental State Exam (MMSE) and the Psychogeriatric Dependency Rating Scale (PGDRS). MethodsParticipants were 198 randomly selected assisted living residents in 22 Maryland facilities. Participants were rated on an 11-item sleep questionnaire regarding insomnia and daytime sleepiness. ResultsSleep disturbance was present in 69% of residents, insomnia (IN) in 42% and excessive daytime sleepiness (DS) in 34.6%. IN and DS scores were not significantly correlated(r = 0.10, p = 0.19). Use of hypnotics, sedating antidepressants, and depression were associated with insomnia. Depression and poor general medical health were associated with daytime sleepiness. On a cognitive task (Mini Mental State Examination) participants with insomnia only out-performed participants with no sleep disturbance and daytime sleepiness; on a measure of physical function (PsychoGeriatric Dependency Rating Scale- physical domain), participants with insomnia fared better than those with daytime sleepiness only and those with both insomnia and daytime sleepiness. Participants with DS only performed worse on both measures compared to those with no sleep disturbance, those with insomnia only, and those with both insomnia and daytime sleepiness. ConclusionThe prevalence of sleep disturbance in AL is similar to that reported in nursing homes. Daytime sleepiness is associated with poorer cognitive and day-to-day functioning, while insomnia is associated with better outcomes. Effective management of DS may lead to improved functioning in the AL residents. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

(See editorial comments by Drs. Kathy Ruckdeschel and Ira Katz on pp 1771–1773)To obtain a direct estimate of the prevalence of dementia and other psychiatric disorders in residents of assisted living (AL) in Central Maryland, and their rates of recognition and treatment.Comprehensive review of history and cognitive and neuropsychiatric evaluations using widely accepted instruments in a randomized cohort of AL residents, stratified by facility size. An expert multidisciplinary consensus panel determined diagnoses and appropriateness of treatment.Twenty-two (10 large and 12 small) randomly selected AL facilities in the city of Baltimore and seven Maryland counties.One hundred ninety-eight volunteers who were residents of AL, 75% were aged 80 and older, and 78% were female. Potential participants were randomly chosen by room number. There was a 67% participation rate.Overall rate of dementia, noncognitive active psychiatric disorders, and recognition and adequate treatment of dementia and psychiatric disorders, as determined by consensus panel.Two-thirds (67.7%) of participants had dementia diagnosable according to theDiagnostic and Statistical Manual of Mental Disorders, Fourth Edition(81% small facilities and 63% large). Family or caregivers recognized 78% to 80% of dementias. Seventy-three percent of dementias were adequately evaluated, and 52% were adequately treated. Of the 26.3% of participants who had an active noncognitive psychiatric disorder, 58% to 61% were recognized and 52% adequately treated.Dementia and psychiatric disorders are common in AL and have suboptimal rates of recognition and treatment. This may contribute to morbidity and interfere with the ability of residents to age in place. [ABSTRACT FROM AUTHOR]

Purpose: Long-term neuropsychological outcome was studied in 71 patients who underwent hemispherectomy for severe and intractable seizures at The Johns Hopkins Hospital between 1968 and 1997 and who agreed to participate. Seizures were due to cortical dysplasias (n = 27), Rasmussen syndrome (n = 37), or vascular malformations or strokes (n = 7). Both presurgical and follow-up results are available and reported for 53 patients. Methods: Patients and caretakers were interviewed, and patients were administered standard measures of intelligence, receptive and expressive language, visual-motor skills, adaptive/developmental functioning, and behavior. Results: Mean age at surgery was 7.2 years. At follow-up, on average 5.4 years after surgery, 65% are seizure free, 49% are medication free, and, of those responding, none rated quality of life as worse than before surgery. Mean IQ was in the 70s for Rasmussen and vascular patients and in the 30s for cortical dysplasia patients. Language and visual-motor skills were consistent with IQ. For Rasmussen patients only, language was significantly more impaired for left than for right hemispherectomy, both before surgery and at follow-up. Adaptive skills were mildly impaired, with greatest impairment in the physical domain. Cognitive measures typically changed little between surgery and follow-up, with IQ change <15 points for 34 of 53 patients; of the remainder, 11 declined and eight improved. Behavior was free of major problems, but social interactions and activities were limited. Conclusions: The most significant predictor of cognitive skills at follow-up was etiology, with dysplasia patients scoring lowest in intelligence and language but not in visual-motor skills. Regardless of etiology, most patients showed only moderate change in cognitive performance at follow-up. [ABSTRACT FROM AUTHOR]

Objective To investigate patient predictors of response to treatment of Major Depressive Episode (MDE) in Alzheimer's disease (AD). Methods Forty-four outpatients with AD and MDE were randomized to receive either sertraline or placebo in a 12-week placebo-controlled, flexible-dose clinical trial after a one week single-blind placebo phase. All participants were evaluated for depression at entry using the 21-item Hamilton Depression Rating Scale (HDRS) and the Cornell Scale for Depression in Dementia (CSDD). All subjects completed baseline neuropsychological testing. Caregiver burden and depression were also measured. The forty-two subjects who completed at least one post-enrollment follow-up visit were included in the analysis. Results No baseline demographic, mood, neuropsychiatric, neuropsychological, or caregiver variable was a statistically significant predictor of response to treatment. There were trends for African-American patients (p =0.07) and those with milder baseline agitation/aggression (p =0.08) to respond better. Conclusion No baseline characteristic assessed clearly predicts response to treatment of MDE in AD. A diverse population of depressed AD patients may thus respond similarly to the same treatment. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD). Methods Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5–10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects. Results Patients on donepezil showed selective and significant (p <0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases. Conclusion Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the course, clinical correlates, and relationship between cognitive status and psycho-pathological features in patients with probable Alzheimer's disease (AD) followed over a 5-year period. DESIGN: Cohort study with follow-up of 5 years. SETTING: Patients were recruited at three sites: 91 patients at Columbia Medical Center, 84 at Johns Hopkins School of Medicine, and 61 at Massachusetts General Hospital. PARTICIPANTS: Patients diagnosed with probable AD (n = 236) enrolled in a longitudinal study (Predictors study). MEASUREMENTS: Wandering/agitation, physical aggression, hallucinations, and delusions were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. Descriptive analyses were used to provide estimates of prevalence and course of psychopathological features. General estimating equations determined the odds of having any of the four psychopathological behaviors as a function of cognitive status. Markov analyses provided 6-month transition probabilities for psychopathological behaviors given patients' cognitive status and the presence or absence of such behaviors in the previous evaluation. RESULTS: For wandering/agitation, prevalence (39-57%) and persistence increased as a function of time and decrement in cognitive status. Physical aggression was less prevalent (6-22%) and increased as a function of cognitive decline but tended to persist only in the more severely impaired patients. Delusions (34-49%) reached a peak at the second year and then declined. The odds of delusions were maximal with intermediate decline but remained persistent regardless of cognitive status. Hallucinations, despite some fluctuations, were relatively stable during the follow-up period (8-17%) and moderately persistent. CONCLUSION: Psychopathological features, particularly wandering/agitation and delusions, in AD were common throughout the disease course. The natural history and persistence of the four... [ABSTRACT FROM AUTHOR]

Background The course of depression in residents of long-term care with dementia is not well studied. Objectives To estimate the incidence, prevalence, and outcomes of depression in long-term care residents with dementia. Method 201 residents of Copper Ridge, a long-term care facility for the memory impaired, were followed every six months during the first year after their admission. Results On admission 19.9% of the residents had depression, the majority (75%) occurring in persons with a prior history of depression. At six months, only 15% of the original 40 depressed patients were still depressed, while at twelve months only 7.5% were depressed. The incidence of depression at six and twelve months was 1.8% and 6.4% respectively. Most persons with new depression at six months were no longer depressed at one year. The annual attack rate (cumulative likelihood of depression over one year) for the total population was 26.4%. The rates for the subgroup of Alzheimer's were similar to the rates of the total population, except for an annual attack rate of 17.5%, reflecting a lower rate of depression on admission. The decline in depression over the year after admission is noteworthy and likely reflects appropriate diagnosis and treatment of depression. Conclusions These results indicate that, over the course of one year, depression afflicts a considerable proportion of long-term care residents with dementia. Admission to a long-term care facility may actually result in a reduction of depression within the year after admission in part due to rapid recognition, appropriate diagnosis and treatment. Copyright © 2002 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Assisted living (AL) is the fastest growing segment of residential long-term care in the US. At least half of the estimated 1 million AL residents have dementia or cognitive impairment, with many AL facilities offering specialized dementia services. Little research has been done on the demographics, outcomes, or clinical variables of this population. Methods Participants were a cohort of 144 residents admitted to the AL unit of Copper Ridge, a specialized dementia-care facility. Comparison samples included 737 patients with dementia residing in other locations (home, nursing home, and other assisted living facilities). Selected measures of cognition, behavior, medical health, and function were taken at admission to AL and at 6-month intervals. Results When compared with residents of the dementia-specialized AL facility, dementia patients at home were younger, less cognitively impaired, and less likely to exhibit wandering, delusions, or aggression. Residents of a dementia-specialized nursing home had more cognitive impairment, greater medical comorbidity, and were more dependent on caregivers. The 2-year mortality rate in the dementia-specialized AL was 23%, significantly lower than rates reported for nursing homes. Primarily due to increasing care needs, most residents in the specialized AL relocated to a nursing home after a median stay of 10.9 months. Depression, falling, and wandering were significant predictors of the transition. Conclusion Dementia-specialized AL facilities occupy a unique position in the long-term care continuum that is distinct from home-care and nursing home facilities. This research is the first step toward understanding the significant dementia population residing in assisted living. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To evaluate variables associated with quality of life (QOL) in dementia residents in a long-term care facility using a recently standardized and validated dementia-specific QOL scale (ADRQL). Method A cross-sectional, case-control design was employed using validated scales to assess dementia-related symptomatology. Thirty-two facility staff members were interviewed to assess the QOL of 120 patients meeting DSM-IV for dementia criteria residing in long-term care. Results ADRQL scores were higher in assisted living residents than in skilled nursing facility residents. In univariate analyses, worse orientation, greater physical dependency, depression, and treatment with anxiolytics were associated with lower ADRQL scores. In multivariate analyses, lower scores were associated with worse orientation, greater physical dependency, depression, and anxiolytic treatment. Conclusions Residents exhibited better QOL than expected. Future longitudinal studies should address if reorientation, activity therapy, treatment of depression, and avoidance of benzodiazepines might improve QOL in this population. Interventions that might improve orientation and physical abilities, such as cholinomimetic therapies, psychosocial interventions, or behavioral strategies, should also be studied in future research on QOL. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim . To evaluate the influence of premorbid personality on adaptation to placement in a long-term care facility. Subjects . Twenty-eight persons with probable Alzheimer disease (AD) residing in an academically affiliated nursing home for 6–9 months. Methods . Premorbid personality was described retrospectively by two informants for each resident using the revised NEO Personality Inventory (NEO-PI-R). Standardized tests and rating scales were used on admission to the facility to assess cognition, mood state, physical dependency and general health. Nurses rated each AD resident's social behaviour, participation in activities and quality of sleep. Results . Poorer adjustment was associated with more severe dementia but better physical health. None of the NEO-PI-R domain scores predicted adjustment. Conclusions . Contrary to popular belief, premorbid personality is relatively inconsequential for an AD patient's adaptation to a long-term care facility. © 1998 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The use of amnesia as a legal defense raises complex issues for both psychology and jurisprudence. Our review of the legal literature suggests that recent advantages in the understanding of clinical disorders of memory have not yet found their way into the courtroom. In this paper, we address the assumptions that amnesia means simply having a very bad memory and that amnesia is a unitary syndrome. We then review recent neuropsychological research on amnesia and its implications for the judicial process. Emphasis is placed on describing the amnesia disorders that most often arise in criminal proceedings. It is concluded that both psychologists and legal professionals should ensure that research findings from the clinic and the laboratory are applied appropriately in cases of defendants claiming amnesia. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether cognitive test performances alone could distinguish patients with probable Alzheimer's disease from those with probable vascular dementia. Sixty-eight outpatients with clinical diagnoses of either Alzheimer's disease or vascular dementia were administered a brief battery of neuropsychological tests. Scores form the Boston Naming Test and the Hopkins Verbal Learning Test were identified as most discriminating of the groups. Seventy-seven per cent of the sample was correctly classified by a stepwise discriminant function analysis. Results of this study indicate that selected neuropsychological tests have moderate concurrent utility in the differential diagnosis of dementia. [ABSTRACT FROM AUTHOR]

We gave 12 cognitively normal, elderly adults (mean age = 76.33 years) training and practice on the Colorado Neuropsychology Tests, a computerized battery of explicit and implicit memory tasks. Half the subjects practiced on the explicit memory tasks for 1.5 hours a week for 9 weeks with the assistance of a psychologist, white the other half practiced on the implicit tasks for the equivalent amount of time. Subjects in both training conditions showed significant improvement within and across training sessions, with those in the implicit memory condition showing the most overall improvement, as indicated by standardized change scores. However, the improved performance on the training tasks did not result in more positive self-assessments of memory capability. In general, subjects displayed favorable attitudes toward the computer technology and were capable of learning to operate the computer software. The results support the practical application of computerized memory training with normal elderly adults. [ABSTRACT FROM AUTHOR]