General Medical Health Rating Research Articles

Pilot trial of Dronabinol adjunctive treatment of agitation in Alzheimer’s disease (THC‐AD)

AbstractBackgroundAgitation in Alzheimer’s Disease (Agit‐AD) is a common and troubling neuropsychiatric syndrome which adds significantly to disability and caregiver stress. Behavioral interventions lack consistent efficacy and there are no FDA‐approved medications. Neurobiological mechanisms that contribute to Agit‐AD include brain atrophy, degradation of neurotransmission, neuroinflammation, disrupted circadian rhythms, comorbidities and frailty. Agit‐AD is a major source of disease progression, patient disability, financial burden, and caregiver stress. Dronabinol is a synthetic cannabinoid (tetrahydrocannabinol, THC). Cannabinoids may improve Agit‐AD by providing protection against neuroinflammation and excitotoxicity, regulating neurotransmitters, improving comorbidities, stabilizing circadian rhythms, and increasing cerebral blood flow.MethodTHC‐AD is a three‐week placebo‐controlled, double‐blind, RCT of dronabinol (10 mg QD) in 80 patients with severe Agit‐AD. Twice daily administration maximizes daytime coverage for agitation and minimizes sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation, and being 60‐95 years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes include a change in the Pittsburgh Agitation Scale and NPI‐C Agitation/Aggression subscales.ResultWe have enrolled 58 out of targeted 80 participants (Table 1: mean age 77.8 years, 65.5% female, 87.9% Caucasian, mean education 13.8 years, 45.6% family history). On average, study participants are very cognitively impaired (Table 2: mean baseline MMSE of 8.1), very agitated (mean NPI‐C Agitation 14.6, mean NPI‐C Aggression 6.3) and in reasonable overall health (Figure 1: General Medical Health Rating, 12.1% “excellent,” 51.7% “good” and 34.5% "fair”). Recorded AEs have been tolerable (Figure 2). Due to the COVID‐19 pandemic, we expanded our inpatient trial to include outpatient enrollments and implemented hybrid visits with telemedicine to limit in‐person interactions. We also added a supplemental study to evaluate the effects of the pandemic on caregiver stress and burden. We are collaborating with additional clinical sites, increasing dementia bed capacity, and deploying recruitment strategies for outpatients, including referrals from providers and other research trials, social media ads, and virtual community outreach.ConclusionSafe and effective interventions for severe agitation are greatly needed. This pilot trial will help to examine the safety and efficacy of dronabinol for Agit‐AD.

Pilot trial of dronabinol adjunctive treatment of agitation in Alzheimer's disease (THC‐AD)

AbstractBackgroundAlthough agitation in Alzheimer’s Disease (Agit‐AD) is a common and troubling neuropsychiatric syndrome, behavioral interventions lack consistent efficacy and there are no FDA‐approved medications. Neurobiological mechanisms that contribute to Agit‐AD include brain atrophy, degradation of neurotransmission, neuroinflammation, disrupted circadian rhythms, comorbidities and frailty. Agit‐AD is a major source of disease progression, patient disability, financial burden, and caregiver stress. Dronabinol is synthetic tetrahydrocannabinol (THC, one of the predominant biochemical constituents of cannabis). Cannabinoids may improve Agit‐AD by providing protection against neuroinflammation and excitotoxicity, regulating neurotransmitters, improving comorbidities, stabilizing circadian rhythms, and increasing cerebral blood flow.MethodTHC‐AD is a three‐week placebo‐controlled, double‐blind, RCT of dronabinol (10 mg QD) in 80 patients with severe Agit‐AD. Twice daily administration maximizes daytime coverage for agitation and minimizes sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation, and being 60‐95 years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes include a change in the Pittsburgh Agitation Scale and NPI‐C Agitation/Aggression subscales.ResultWe have enrolled 37 out of 80 participants (Table 1: mean age 78.2 years, 78.4% female, 83.8% Caucasian, mean education 13.2 years, 48.6% family history). Study participants are significantly cognitively impaired (Table 2: mean baseline MMSE of 7.1), agitated (mean NPI‐C Agitation 14.8, mean NPI‐C Aggression 6.4) and in reasonable overall health (Figure 1: General Medical Health Rating, 10.8% “excellent,” 48.6% "good" and 40.5% "fair”). Recorded AEs have been tolerable (Figure 2). Due to the COVID‐19 pandemic, we expanded our inpatient trial to include outpatient enrollments and implemented hybrid visits with telemedicine to limit in‐person interactions. To bolster our recruitment, we are collaborating with additional clinical sites, increasing dementia bed capacity, and deploying recruitment strategies for outpatients, including referrals from providers and other research trials, social media ads, and virtual community outreach. Updated results will be presented at AAIC (estimated 6‐10 additional participants).ConclusionSafe and effective interventions for severe agitation are greatly needed. This pilot trial will help to examine the safety and efficacy of dronabinol for Agit‐AD.

Pilot Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer's Disease (THC-AD)

<h3>Introduction</h3> Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging (70%). Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course (97%). One of the most troubling NPS is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. Neurobiological mechanisms that contribute to Agit-AD include brain atrophy, degradation of neurotransmission, neuroinflammation, disrupted circadian rhythms, comorbidities, and frailty. There is a great need for better interventions that target Agit-AD, which is a major source of disease progression, patient disability, financial burden, and caregiver stress. Dronabinol is synthetic tetrahydrocannabinol (THC, one of the predominant biochemical constituents of cannabis) and is FDA approved for anorexia and nausea. Cannabinoids may improve Agit-AD by providing protection against neuroinflammation and excitotoxicity, regulating neurotransmitters, improving comorbidities, stabilizing circadian rhythms, and increasing cerebral blood flow. This pilot trial could open the door to "re-purposing" dronabinol as a novel and safe treatment for Agit-AD with significant public health impact. <h3>Methods</h3> THC-AD is a three-week placebo-controlled, double-blind, randomized clinical trial of dronabinol (10 mg QD) in 80 patients with severe Agit-AD. Capsules of dronabinol contain 2.5 mg per dose (5 mg daily) during Week 1, then increase to 5 mg per dose (10 mg daily) for Weeks 2 and 3. The half-life of dronabinol is ∼4 hours, so study medication is administered BID at 08:00 and 14:00 to maximize daytime coverage for agitation and to minimize sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation as determined by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), and being 60-95 years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes are a change in the Pittsburgh Agitation Scale and NPI-C Agitation/Aggression subscales. Secondary outcomes are measures of agitation, cognition, sleep, and global functioning as determined by the following assessments: the NPI-C, Cohen Mansfield Agitation Inventory, Clinical Global Impression of Change, Activities of Daily Living, Mini-Mental State Examination (MMSE), Severe Impairment Battery (8 item), and subjective and observer-rated drug effects. Safety outcomes include monitoring for adverse events (AEs), weekly health assessments, EKG changes, incident delirium (Confusion Assessment Method), and changes in laboratory values. DNA specimens are collected to explore cannabinoid receptor polymorphisms that may affect response to dronabinol. Serum samples are collected to examine the association of peripheral markers of inflammation with agitation and response to dronabinol. Concomitant medications are limited to currently used antipsychotics, antidepressants, and benzodiazepines, as well as anticonvulsant therapy when not used for seizure disorder. PRN rescue medications include total daily doses up to 0.75 mg of lorazepam and 100 mg of trazodone. <h3>Results</h3> We have enrolled 37 out of 80 participants (Table 1: mean age 78.2 years, 78.4% female, 83.8% Caucasian, mean education 13.2 years, 48.6% family history). Study participants are significantly cognitively impaired (Table 2: mean baseline MMSE of 7.1), agitated (mean NPI-C Agitation 14.8, mean NPI-C Aggression 6.4) and in reasonable overall health (Figure 1: General Medical Health Rating, 10.8% "excellent," 48.6% "good" and 40.5% "fair"). Recorded AEs have been tolerable (Figure 2). Due to the COVID-19 pandemic, we expanded our inpatient trial to include outpatient enrollments and implemented hybrid visits with telemedicine to limit in-person interactions. To bolster our recruitment, we are collaborating with additional clinical sites, increasing dementia bed capacity, and deploying recruitment strategies for outpatients, including referrals from providers and other research trials, social media ads, and virtual community outreach. Updated results will be presented at AAGP (estimated 6-10 additional participants). <h3>Conclusions</h3> Agitation is one of the most common behavioral manifestations of AD and is associated with greater caregiver burden and shorter time to institutionalization. Current treatments for Agit-AD have a plethora of safety limitations, and there is a particularly acute need for interventions for severe Agit-AD in advanced dementia. One important question for treatment development is whether Agit-AD represents a specific target for intervention or a nonspecific syndrome shared with many other diseases. This clinical trial may enable us to understand if targeting the cannabinoid system will be a safe and effective approach to treat this global health concern. <h3>Funding</h3> National Institute on Aging, R01AG050515

TRIAL OF DRONABINOL ADJUNCTIVE TREATMENT OF AGITATION IN ALZHEIMER'S DISEASE (AD) (THC-AD)

Introduction Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging. Neuropsychiatric symptoms (NPS) in AD are a major cause of burden to patients, caregivers, and society and are near-universal at some point in the AD course. One of the most troubling of these symptoms is agitation (Agit-AD), typified by a variety of problem behaviors including combativeness, yelling, pacing, lack of cooperation with care, insomnia, and restlessness. There is a great need for better interventions that target Agit-AD, a major source of patient disability as well as caregiver burden and stress, particularly in the case of moderate to severe agitation. Dronabinol (Marinol®) is synthetic tetrahydrocannabinol (THC, one of the predominant biochemical constituents of cannabis), which produces anxiolytic, antidepressant, and anti-inflammatory effects and is FDA approved for anorexia and nausea. This pilot trial could open the door to re-purposing dronabinol as a novel and safe treatment for Agit-AD with significant public health impact. Methods THC-AD is a three-week placebo-controlled, double-blind, randomized clinical trial of dronabinol (10?mg QD) in 80 inpatients, assisted living facility (ALF), or nursing home residents with severe Agit-AD. Capsules of dronabinol contain 2.5?mg per dose (5?mg daily) during Week 1, then increase to 5?mg per dose (10?mg daily) for Weeks 2 and 3. The half-life of dronabinol is ∼4?hours, so study medication is administered BID at 08:00 and 14:00 to maximize daytime coverage for agitation and to minimize sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation as determined by the Neuropsychiatric Inventory-Clinician Rating Scale (NPI-C), and being 60-95?years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes include a change in the Pittsburgh Agitation Scale and NPI-C Agitation/Aggression subscales. Secondary outcomes include measures of agitation, cognition, sleep, and global functioning as determined by the following assessments: the NPI-C, Cohen Mansfield Agitation Inventory, Clinical Global Impression of Change, Activities of Daily Living, Mini-Mental State Examination (MMSE), Severe Impairment Battery (8 item), and subjective and observer-rated drug effects. Safety outcomes include monitoring for adverse events (AEs), weekly health assessments, EKG changes, incident delirium (Confusion Assessment Method), and changes in laboratory values. DNA specimens are collected to explore the possibility that cannabinoid receptor polymorphisms may affect response to dronabinol. Serum samples are collected to examine the association of peripheral markers of inflammation with agitation and response to dronabinol. Concomitant medications are limited to currently used antipsychotics, antidepressants, and benzodiazepines, as well as anticonvulsant therapy when not used for seizure disorder, with lorazepam 0.75?mg QD total daily allowed as rescue medication, and can be administered orally or intramuscularly. Additionally, PRN trazodone in doses up to 100?mg total daily dose are allowed for agitation and insomnia. Results We began recruitment in March, 2017 and have enrolled 27 out of 80 participants (mean age 76.96?years, 77.8% female, 85.2% Caucasian, mean total education completed 13.84?years, 55.6% family history of memory impairment). Study participants are significantly cognitively impaired (mean baseline MMSE of 6.69), agitated (mean NPI-C Agitation subtotal 15.19, mean NPI-C Aggression subtotal 6.48) and in reasonable overall health (General Medical Health Rating, 51.9% good and 40.7% fair.) The pace of recruitment is behind initial projections due to a number of factors including adaptation of inpatient units to a culture of research, cost of study medication post clinical trial, difficulty swallowing over-encapsulated pills, prior or current treatment with dronabinol and patient acuity leading to protocol deviations. To meet our recruitment target, we are launching our trial at additional locations (including ALF and nursing homes) and we have expanded the inclusion criteria to increase the maximum age at study entry to 95?years. We have not encountered adverse events or regulatory issues that suggest a rationale to change our study protocol. Conclusions AD is a fatal disease which robs an individual of their memory and personality. Agitation is one of the most common behavioral manifestations of AD and is associated with greater caregiver burden and shorter time to institutionalization. Current treatments for Agit-AD have a plethora of safety limitations, and there is a particularly acute need for interventions for severe Agit-AD in advanced dementia. One important question for treatment development is whether Agit-AD represents a specific target for intervention or a nonspecific syndrome shared with many other diseases. This clinical trial may enable us to understand if targeting the cannabinoid system will be an effective approach to treat this public health issue. This research was funded by: National Institute of Aging, R01AG050515

Correlates of daily functioning in older adults with autism spectrum disorder

Objectives: Studies of adults with autism spectrum disorder (ASD) have demonstrated poor outcomes related to independence and everyday living skills compared to the general population. In a sample of 74 adults with ASD who require a high level of support we sought to identify correlates of daily functioning.Methods: We administered questionnaires to residential staff and identified participants’ independence level in basic and instrumental activities of daily living.Results: There was no association of age with daily functioning. Higher daily functioning was associated with a better general medical health rating. Functional independence was greater in participants with IQ range of 55 to 65 compared to those with IQ below 55. Language difficulties and behavioral disturbances were not significantly correlated with independence in daily living skills. In this sample, individual had held a median of three different types of jobs in supported employment.Conclusion: Daily functioning in adults with autism generally does not decline with age, but because this was cross-sectional data, this requires further confirmation. Community programs designed for adults with ASD who require a high level of support should focus on overall medical health and promotion of daily living skill building.

Physical diagnoses in nursing home residents - is dementia or severity of dementia of importance?

BackgroundDementia and physical morbidity are primary reasons for nursing home admission globally. However, data on physical morbidity in nursing home residents with and without dementia are scarce. The first aim of the present study was to explore whether presence and severity of dementia were related to the number of physical diagnoses in nursing home residents. The second aim was to explore if the severity of dementia was associated with having registered the most frequent complexes of physical diagnoses when controlling for physical health and demographic factors.MethodsA total of 2983 Norwegian nursing home residents from two cross-sectional samples from 2004/2005 and 2010/2011 were included in the analysis. By the use of assessment scales, the severity of dementia (Clinical Dementia Rating), physical health (General Medical Health Rating), activities of daily living (Physical Self-Maintenance Scale) and neuropsychiatric symptoms (Neuropsychiatric Inventory Nursing Home) were determined. Physical diagnoses and medications were assembled from the medical records. The physical diagnoses were categorized into complexes, using the ICD-10 chapters. Linear mixed models and generalized linear mixed models were estimated.ResultsResidents with dementia were registered with fewer physical diagnoses than residents without dementia. The frequency of physical diagnoses decreased with increasing severity of dementia. Cardiovascular, musculoskeletal and endocrine, nutritional and metabolic diagnoses were the most common complexes of physical diagnoses in individuals with and without dementia. The odds of having cardiovascular and musculoskeletal diagnoses increased for males and decreased for females with increasing severity of dementia, in contrast to endocrine diagnoses where the odds increased for both genders.ConclusionIncreasing severity of dementia in nursing home residents may complicate the diagnostics of physical disease. This might reflect a need for more attention to the registration of physical diagnoses in nursing home residents with dementia.

Health-related quality of life in older depressed psychogeriatric patients: one year follow-up

BackgroundKnowledge about long-term change in health related quality of life (HQoL) among older adults after hospitalization for treatment of depression has clinical relevance. The aim was firstly to describe the change of HQoL one year after admission for treatment of depression, secondly to explore if improved HQoL was associated with remission of depression at follow-up and lastly to study how HQoL in patients with remission from depression were compared to a reference group of older persons without depression.MethodThis study had the one year follow-up information of 108 older patients (≥60 years), all hospitalized for depression at baseline, and a reference sample of 106 community-living older adults (≥60 years) without depression. HQoL was measured using the EuroQol Group’s EQ-5D Index and a visual analog scale (EQ-VAS). Depression and remission were diagnosed according to ICD-10. Socio-demographic variables (age, gender, and education), depressive symptom score (Montgomery-Aasberg Depression Rating Scale), cognitive functioning (Mini Mental State Examination scale), instrumental activities of daily living (the Lawton and Brody’s Instrumental Activities of Daily Living Scale), and poor general physical health (General Medical Health Rating) were included as covariates.ResultsHQoL had improved at follow-up for the total group of depressed patients, as indicated by better scores on the EQ-5D Index and EQ-VAS. In the multivariate linear regression model, improved EQ-5D Index and EQ-VAS was significantly better in those with remission of depression and those with better baseline physical health. In adjusted analyses, the HQoL in patients with remission from depression at follow-up did not differ from the HQoL in a reference group without depression.ConclusionOlder hospital patients with depression who experienced remission one year after admission gained HQoL and their HQoL was comparable with the HQoL in a reference group of older adults without depression when adjusting for differences in socio-demographics and health conditions.

The association between general medical health and course of cognition, function, and neuropsychiatric symptoms in the cache county dementia progression study

A number of studies suggest a link between health status and dementia course in individuals with Alzheimer's disease (AD). We investigated the relationships between measures of health and changes in cognition, function, and neuropsychiatric symptoms in a population-baed study of incident AD. We used data from the population-based Cache County study of memory and aging (CCSMA). The sample included 335 individuals with incident AD who were followed for up to eleven years. Measures of health status at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating – sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). Two types of longitudinal mixed effects were fit: in the first, differences in course over time on the dementia outcomes was modeled as a function of baseline health; in the second, outcomes at each timepoint were measured as a function of health at the same timepoint. All models were adjusted for sex, age, education, dementia duration at baseline, and APOE genotype. individuals demonstrated both improvements and worsening of their health status over time. Neither GMHR nor comorbidities, and non-psychiatric medications at baseline were associated with differences in rates of decline. Over time, lower GMHR ratings at a given visit were associated with worse outcomes at that same visit (MMSE: β = –1.07 p = 0.01; CDR-sb: β = 1.79 p < 0.001; NPI: β = 4.57 p = 0.01). Given that time-varying GMHR, but not baseline GMHR, was associated with each of the outcomes it seems likely that the effect is a dynamic one, but potentially modifiable. Further study, including randomized trials of dementia care models, is needed to establish the direction of causality and the efficacy of improving health as a means of ameloriating the effects of AD.

The Agreement between the MMSE and IQCODE Tests in a Community-Based Sample of Subjects Aged 70 Years or Older Receiving In-Home Nursing: An Explorative Study

Aim: It was the aim of this study to compare the Mini-Mental State Examination (MMSE) with the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) and to explore the characteristics of subjects with possible dementia with only one of the two tools. Methods: We used a random sample of patients aged 70+ receiving social service or in-home nursing. The patients were tested with the MMSE, and the next of kin was interviewed using the following: the IQCODE, the Cornell Scale for Depression in Dementia (CSDD), the Neuropsychiatric Inventory (NPI), instrumental activities of daily living (IADL), personal ADL (PADL) and the General Medical Health Rating (GMHR). Results: Subjects with dementia defined only according to the MMSE showed a pattern of scores on IADL, PADL, CSDD, NPI-10 and GMHR similar to the no-dementia group according to both the MMSE and the IQCODE. Those with dementia defined only according to the IQCODE showed a pattern of scores similar to the possible dementia group according to both the MMSE and the IQCODE.

Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's dementia and death: the Cache County Dementia Progression Study.

Little is known about factors influencing the rate of progression of Alzheimer's dementia. Using data from the Cache County Dementia Progression Study, the authors examined the link between clinically significant neuropsychiatric symptoms in mild Alzheimer's dementia and progression to severe dementia or death. The Cache County Dementia Progression Study is a longitudinal study of dementia progression in incident cases of this condition. Survival analyses included unadjusted Kaplan-Meier plots and multivariate Cox proportional hazard models. Hazard ratio estimates controlled for age at dementia onset, dementia duration at baseline, gender, education level, General Medical Health Rating, and apolipoprotein E epsilon 4 genotype. Three hundred thirty-five patients with incident Alzheimer's dementia were studied. Sixty-eight (20%) developed severe dementia over the follow-up period. Psychosis (hazard ratio=2.007), agitation/aggression (hazard ratio=2.946), and any one clinically significant neuropsychiatric symptom (domain score ≥4, hazard ratio=2.682) were associated with more rapid progression to severe dementia. Psychosis (hazard ratio=1.537), affective symptoms (hazard ratio=1.510), agitation/aggression (hazard ratio=1.942), mildly symptomatic neuropsychiatric symptoms (domain score of 1-3, hazard ratio=1.448), and clinically significant neuropsychiatric symptoms (hazard ratio=1.951) were associated with earlier death. Specific neuropsychiatric symptoms are associated with shorter survival time from mild Alzheimer's dementia to severe dementia and/or death. The treatment of specific neuropsychiatric symptoms in mild Alzheimer's dementia should be examined for its potential to delay time to severe dementia or death.

Predictors of Cognitive Improvement in Persons with Cognitive Impairment: A Naturalistic Study

Introduction: Dementia has traditionally been known as a progressive illness, but with earlier detection of cognitive impairment, clinicians have observed a more variable course. The literature has suggested that depression, anxiety, apathy, psychosis, disinhibition, and nighttime behaviors may be associated with both improvement and decline in cognition but it remains inconclusive. In this study we looked at factors that may predict improvement in MMSE score at later follow up. Methods: Patients from the Brooklyn Alzheimer’s Disease Assistance Center who were evaluated for cognitive impairment were included in the study. The sample consisted of 98 people who were evaluated on their 3rd visit (mean1⁄4243 days) and 85 people evaluated at their 4th visit (mean1⁄4366 days). Mean age was 77.6 years; 77% was female; 69% were Black, 14% were White, and 13% were Latino. The outcome measure of interest was the change in MMSE score from intake to the 3rd or 4th follow up visits. The diagnoses included in the study were Dementia, Alzheimer’s type, Vascular dementia, Mixed dementia and other diagnoses. Based on preliminary analyses and a literature review, 9 predictors of outcome were identified: age, gender, Black race, general medical condition, hypertension, nighttime behavioral disturbance, receiving a cognitive enhancer, receiving an antipsychotic medication, and MMSE score at evaluation. Results: 72.9% of the clinic population were diagnosed with Dementia, Alzheimer’s type, 9.6% with Vascular dementia, 6.5% with Mixed Dementia and 11% had other diagnoses. 38% and 32% of patients had an “improved” MMSE score of 3 or more points at the 3rd and 4th visits, respectively. Variables included in the linear regression analysis of the third visit included age, gender, Black race, General Medical Health rating, history of hypertension, receiving a cognitive enhancer at the third visit, receiving an antipsychotic at the third visit and initial MMSE. Black race (t1⁄42.822, p1⁄4.007), lack of hypertension (t1⁄4-2.180, p1⁄4.034), lower MMSE score at intake (t1⁄4-2.732, p1⁄4.008) were significantly associated with improvement in MMSE score at the 3rd visit. Variables included in the linear regression analysis of the fourth visit included age, gender, Black race, General Medical Health rating, history of hypertension, receiving a cognitive enhancer at the fourth visit, receiving an antipsychotic at the fourth visit and initial MMSE. Only the MMSE at intake (t1⁄4-4.113, p1⁄4.000) was significantly associated with improvement in MMSE at the fourth visit. Conclusions: Contrary to expectations, this naturalistic study found that nearly two-fifths and one-third of dementia patients were improved at approximately 8 months and 12 months after follow-up, respectively. Black race was associated with improved MMSE score at the 3rd visit consistent with past literature that suggests Black patients may have a more variable course of cognitive decline. The effect of Black race may also explain the high percentage of patients with improved cognition in our population. In addition normal or lower blood pressure was associated with improvement in MMSE at the third visit perhaps highlighting the role of blood pressure control in preventing progression of cognitive impairment. These findings suggest, in an outpatient setting, patients with cognitive complaints may have better outcomes in terms of cognition than previously thought.

Effects of general medical health on Alzheimer's progression: the Cache County Dementia Progression Study

Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimer's disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression. This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah. Participants comprised 335 individuals with incident AD followed for up to 11 years. Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating - sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). Health status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, and non-psychiatric medications) was associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β = -1.07 p = 0.01; CDR-sb: β = 1.79 p < 0.001; NPI: β = 4.57 p = 0.01). Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, it seems likely that there is a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted.

Predictors of quality of life ratings for persons with dementia simultaneously reported by patients and their caregivers: the Cache County (Utah) Study

Quality of life (QOL) is frequently assessed in persons with dementia (PWD) through self- and/or proxy-report. Determinants of QOL ratings are multidimensional and may differ between patients and caregiver proxies. This study compared self- and proxy-reported QOL ratings in a population-based study of PWD and their caregivers, and examined the extent to which discrepancies in reports were associated with characteristics of the PWD. The sample consisted of 246 patient/caregiver dyads from the initial visit of the Cache County Dementia Progression Study, with both members of the dyad rating PWD QOL. PWD age, gender, cognitive impairment (Mini-Mental State Examination), neuropsychiatric symptoms (Neuropsychiatric Inventory; NPI), dementia severity (Clinical Dementia Rating), medical comorbidities (General Medical Health Rating), and functional impairment (Dementia Severity Rating Scale) were examined as correlates of self- and proxy-reported QOL ratings and the differences between the QOL reports. Self- and proxy-reported PWD QOL ratings were only modestly correlated. Medical comorbidity was associated with self-report whereas NPI was associated with proxy-report. Dementia severity was associated with discrepancies in self- and proxy-report, with worse patient cognition associated with poorer proxy-reported QOL ratings. PWD self- and proxy-reported QOL ratings are associated with different variables. Discrepancies between PWD and caregiver perceptions of PWD QOL should be recognized, particularly in cases of more severe dementia.

Acetylcholinesterase inhibitors in assisted living: patterns of use and association with retention

To describe patterns of Acetylcholinesterase inhibitor (ACI) use in an Assisted Living (AL) population, and the association of ACIs with retention in AL. 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. 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. ACIs have low rates of use in AL and are associated with better retention for residents with AD.

Population-Based Study of Medical Comorbidity in Early Dementia and "Cognitive Impairment, No Dementia (CIND)": Association With Functional and Cognitive Impairment: The Cache County Study

Authors investigated medical comorbidity in persons with dementia and "Cognitive Impairment, No Dementia" (CIND). The Cache County Study is an ongoing population-based study of the epidemiology of dementia, the risk factors for conversion from CIND to dementia, and the progression of dementia. As part of the study's first incidence wave, persons with dementia (N=149), CIND (N=225), or without cognitive impairment (N=321) were identified and studied. Participants received comprehensive clinical evaluations and were rated on the General Medical Health Rating (GMHR), a global measure of seriousness of medical comorbidity. Participants and informants also completed the Mini-Mental State Exam and provided self-report information about comorbid medical conditions and functioning in activities of daily living. There were few differences in number or type of comorbid medical conditions between persons with CIND and dementia, but persons with dementia were prescribed more medications. Stroke was more common in dementia participants, but other illnesses common in old age were not significantly different across cognitive groups. Medical comorbidity was more serious in both dementia and CIND, such that both groups were less likely to have "little to no" comorbidity. Seriousness of medical comorbidity was significantly associated with worse day-to-day functioning and cognition. Persons with CIND and dementia have more serious medical comorbidity than comparable persons without cognitive impairment. This comorbidity may play a role in the progression of CIND and dementia. Future studies should investigate the role of medical comorbidity and its treatment on dementia onset or progression, as well as the mechanisms mediating its neuropathologic effects.

Population-Based Study of Medical Comorbidity in Early Dementia and “Cognitive Impairment, No Dementia (CIND)”: Association With Functional and Cognitive Impairment: The Cache County Study

Authors investigated medical comorbidity in persons with dementia and "Cognitive Impairment, No Dementia" (CIND).The Cache County Study is an ongoing population-based study of the epidemiology of dementia, the risk factors for conversion from CIND to dementia, and the progression of dementia. As part of the study's first incidence wave, persons with dementia (N=149), CIND (N=225), or without cognitive impairment (N=321) were identified and studied. Participants received comprehensive clinical evaluations and were rated on the General Medical Health Rating (GMHR), a global measure of seriousness of medical comorbidity. Participants and informants also completed the Mini-Mental State Exam and provided self-report information about comorbid medical conditions and functioning in activities of daily living.There were few differences in number or type of comorbid medical conditions between persons with CIND and dementia, but persons with dementia were prescribed more medications. Stroke was more common in dementia participants, but other illnesses common in old age were not significantly different across cognitive groups. Medical comorbidity was more serious in both dementia and CIND, such that both groups were less likely to have "little to no" comorbidity. Seriousness of medical comorbidity was significantly associated with worse day-to-day functioning and cognition.Persons with CIND and dementia have more serious medical comorbidity than comparable persons without cognitive impairment. This comorbidity may play a role in the progression of CIND and dementia. Future studies should investigate the role of medical comorbidity and its treatment on dementia onset or progression, as well as the mechanisms mediating its neuropathologic effects.

Medical Comorbidity in Psychiatric Inpatients: Relation to Clinical Outcomes and Hospital Length of Stay

Medical comorbidity is common in psychiatric inpatients and may be associated with substantial impairment and mortality. Few studies have examined the relation between this comorbidity and psychiatric outcomes. A series of 950 admissions to the Johns Hopkins Hospital Phipps Psychiatric Service were rated by attending psychiatrists at admission and discharge on symptom and functional measures. A subset was also evaluated on the General Medical Health Rating, a valid and reliable measure of seriousness of medical comorbidity. Attending psychiatrists were also asked at discharge whether medical comorbidity had been a focus of care during the hospitalization; medical comorbidity had been a focus of care in about 20% of the patients. Serious active medical comorbidity was present in 15% of patients on admission and 12% at discharge. Medical comorbidity was associated with a 10%-15% increase in psychiatric symptoms and functional impairment at discharge, even after adjustment for admission clinical status. In addition, when comorbidity had been a focus of care during the hospitalization, length of stay was prolonged by 3.25 days on average. Medical comorbidity has measurable effects on the psychiatric outcomes of psychiatric inpatients and in some cases prolongs hospital stay. Psychiatrists should redouble their efforts to detect and treat this comorbidity and should consider whether special inpatient units might be needed to care for psychiatric patients with complex medical comorbidity.

The General Medical Health Rating: a bedside global rating of medical comorbidity in patients with dementia.

Dementia is a serious public health problem. General medical comorbidity is common in dementia patients and critical to their care. However, little is known about medical comorbidity in these patients, and there are no straightforward bedside global rating scales for the seriousness of comorbid medical illness. This paper describes the development and measurement properties of the General Medical Health Rating (GHMR), a rapid global rating scale of medical comorbidity in dementia patients. Interrater reliability, concurrent validity, and predictive validity of the GMHR are reported. An outpatient dementia clinic, assisted living, and nursing home. A total of 819 consecutive dementia clinic outpatients and 180 consecutive admissions to Copper Ridge, a long-term care residence for people with dementia, were included in the study. GMHR was found to be highly reliable (weighted kappa = .91). Across all stages and types of dementia, GMHR ratings were correlated with number of comorbid medical conditions, number of medications being taken for comorbid conditions, and with activity of daily living impairment, even after adjustment for severity of dementia. GMHR ratings were also a strong predictor of falls and of mortality in long-term care residents after adjustment for age and severity of dementia. GMHR is a reliable, valid, global bedside measure of severity of general medical comorbidity for patients with dementia that can be used for clinical and research purposes.

Wandering behaviour in community-residing persons with dementia.

To examine wandering behaviour in elderly demented persons in the community setting with respect to dementia characteristics and other factors that might influence wandering behaviour; to generate a statistical model to assess the relative importance of these various factors in predicting wandering behaviour. Cross-sectional, case-control investigation. University-affiliated outpatient neuropsychiatric assessment center. Six hundred and thirty-eight consecutive community-residing new patients with dementia referred for evaluation. Comprehensive neuropsychiatric evaluation, including rating with Mini-Mental State Examination; General Medical Health Rating; Comell Scale of Depression in Dementia and caregiver interview. Wandering behaviour occurred in 17.4% of participants. It was significantly more prevalent in patients with Alzheimer Dementia (AD), patients with dementia of longer duration, and patients with more severe dementia. Wandering behaviour was associated with moderate to severe depression, delusions, hallucinations, and sleep disorder. Other significant associations of wandering behaviour included use of neuroleptic medication and male gender. After statistical adjustment for other variables, duration of dementia, severity of dementia and presence of sleep disorder retained significant statistical association with wandering behaviour. Wandering behaviour among community-residing elderly dementia patients is associated with a number of factors, some of which may be subject to modification. It is possible that management of coexistent psychopathology, particularly of sleep disorder, and of the underlying disease process of AD would help to ameliorate this problematic behavioural disorder. Further investigation is warranted into the relationship between neuroleptic medication and wandering behaviour and into possible alternative measures to control agitation in elderly dementia patients.