Sleep disorders and their impacts on healthy, dependent, and frail older adults.

BACKGROUND: Sleep disorders differ widely in the heterogeneous older adult population. Older adults can be classified into three groups based upon their overall level of disability: healthy, dependent, and frail. Frailty is an emerging concept that denotes older persons at increased risk for poor outcomes. OBJECTIVE: The aim of this consensus review is to describe the sleep disorders observed in healthy and dependent older adults and to discuss the potential sleep disorders associated with frailty as well as their potential consequences on this weakened population. METHODS: A review task force was created including neurologists, geriatricians, sleep specialists and geriatric psychiatrists to discuss age related sleep disorders depending on the three categories of older adults. All published studies on sleep in older adults on Ovid Medline were reviewed and 106 articles were selected for the purpose of this consensus. RESULTS: Many healthy older adults have complains about their sleep such as waking not rested and too early, trouble falling asleep, daytime napping, and multiple nocturnal awakenings. Sleep architecture is modified by age with an increased percentage of time spent in stage one and a decreased percentage spent in stages three and four. Insomnia is frequent and its mechanisms include painful medical conditions, psychological distress, loss of physical activity and iatrogenic influences. Treatments are also involved in older adults' somnolence. The prevalence of primary sleep disorders such as restless legs syndrome, periodic limb movements and sleep disordered breathing increases with age. Potential outcomes relevant to these sleep disorders in old age include mortality, cardiovascular and neurobehavioral co-morbidities. Sleep in dependent older adults such as patients with Alzheimer Disease (AD) is disturbed. The sleep patterns observed in these patients are often similar to those observed in non-demented elderly but alterations are more severe. Nocturnal sleep disruption and daytime sleepiness are the main problems. They are the results of Sleep/wake circadian rhythm disorders, environmental, psychological and iatrogenic factors. They are worsened by other sleep disorders such as sleep disordered breathing. Sleep in frail older adults per se has not yet been formally studied but four axes of investigation should be considered: i) sleep architecture abnormalities, ii) insomnia iii) restless legs syndrome (RLS), iv) sleep disordered breathing. CONCLUSION: Our knowledge in the field of sleep disorders in older adults has increased in recent years, yet some groups within this heterogeneous population, such as frail older adults, remain to be more thoroughly studied and characterized.

Depression, diabetes and metabolic-nutritional factors in elderly Hispanics.

OBJECTIVE: To examine the relationship of depression to metabolic and nutritional risk factors in older Hispanics. DESIGN: Crossectional study. SETTING: Subjects were part of a community-based, cognitive evaluation project that examined 301 subjects in the Eastern San Fernando Valley of Southern California. PARTICIPANTS: Two elderly Hispanic groups: 53 clinically depressed, with memory complaints but not demented subjects, and 33 generally healthy, cognitively asymptomatic subjects. MEASUREMENTS: The results of functional and nutritional questionnaires, a medical and neurological examination, 12-hour fasting clinical laboratory tests, MRI or CT scans, and neuropsychological testing. RESULTS: Both groups were nearly identical along socio-demographic variables. However, the depressed group differed significantly from the general healthy group not only in percent of diabetics (38% vs.18%), but in the amount of poorly controlled diabetes, and the depressed group consumed about half the amount of fish that the generally healthy group did. CONCLUSIONS: This study suggests that factors such as poorly controlled diabetes combined with low consumption of foods high in omega-3 fatty acid content such as sea fish may be associated with an increased risk of developing depression in late life. These factors may be socio-economically and culturally influenced and are therefore amenable to modification.

Frequency of Alzheimer's disease and other dementias in a community outreach sample of Hispanics.

OBJECTIVES: To determine the proportion of Alzheimer's disease (AD) and other dementia types in a community sample of Hispanics. DESIGN: This is a descriptive diagnostic study of a nonrandom community outreach sample utilizing established criteria for the diagnosis of dementia type. Recruitment involved direct community outreach with diagnostic evaluations conducted at a university-affiliated outpatient clinic. SETTING: Hispanic Neuropsychiatric and Memory Research Clinic at the Olive View-UCLA Medical Center in Sylmar, California. PARTICIPANTS: One hundred community-dwelling Hispanics age 55 and older without prior diagnosis or treatment of their cognitive symptoms. MEASUREMENTS: Each subject underwent a complete medical diagnostic evaluation, in Spanish, including neuropsychological tests, neurological examination, laboratory tests, and brain imaging (computed tomography or magnetic resonance imaging) to establish dementia type. Presence of dementia was established according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Diagnosis for probable or possible AD and vascular dementia (VascD) was established using criteria from the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable AD and by research criteria from the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences for VascD, respectively. Frontotemporal dementia was diagnosed using recommendations set forth by the Lund and Manchester groups. RESULTS: Subjects were poor, with low acculturation levels despite long years of U.S. residence. Forty percent of subjects had had undiagnosed cognitive symptoms for 3 or more years. Of those demented, 38.5% had AD and 38.5% met criteria for VascD. The best predictors of VascD were hypertension and cerebrovascular disease, whereas apolipoprotein E4 allele best predicted AD. Other forms of dementia were also present. Twenty percent of the sample was clinically depressed but not demented. CONCLUSIONS: In comparison with data from predominantly white populations, our proportion of AD cases was lower and that of VascD cases was considerably higher than anticipated. The percentage of clinically depressed older individuals was also high. These findings could have implications for differential cultural and genetic risk factors for dementia among diverse ethnic/racial groups. Further studies are needed to obtain accurate prevalence estimates of dementing disorders among the different U.S. Hispanic populations.

Barriers to healthcare access for cognitively impaired older Hispanics.

This study describes the development of the Barriers to Healthcare Access Survey (BHAS) used to evaluate seven barrier factors believed to influence healthcare access for elderly Hispanics with memory or cognitive problems. This study further reports the results of the BHAS applied to a community sample of cognitively impaired older Hispanics and their caregivers. The study includes (1) The BHAS's development and procedures to establish instrument validity and reliability; (2) Interviews with the BHAS on 65 cognitively impaired Hispanics who were undergoing full diagnostic assessment for dementia and their caregivers. The most frequently perceived healthcare barriers reported in our study were related to (1) personal beliefs (38%), (2) language proficiency (33%), and (3) economic status (13%). The BHAS possesses the requisite psychometric properties to be an effective instrument for an initial survey of perceived barriers to access health care for low-education, cognitively impaired, elderly Hispanic patients. The findings suggest that perceptions regarding illness, health consequences of aging, and beliefs about the utility of medicine do, in fact, influence healthcare use by older Hispanic patients with dementia. Language proficiency and economic status remain common barriers among elderly Hispanic subgroups, but when these barriers are experienced by the cognitively impaired, serious healthcare implications ensue, especially delay in early diagnosis and treatment.

Effects of muscarinic and adrenergic agonism on auditory P300 in the macaque.

Homologs of human endogenous evoked potentials are known in several species of nonhuman primates, but the neurotransmitter substrates of these potentials remain uncertain. In particular, the role of central cholinergic and adrenergic systems is not yet clearly defined. We recorded cognitive evoked potentials from the scalp in four adult bonnet macaque monkeys during a passive version of the auditory oddball paradigm with unique novel stimuli under saline control conditions. In two subjects each, cognitive evoked potentials were also recorded following intramuscular administration of the m1 muscarinic agonist AF102B or of the alpha-2A noradrenergic agonist guanfacine. On saline, large positivities resembling the human P300 were recorded over midline sites in response to rare or novel auditory stimuli in all four monkeys. The amplitude of these positivities was sensitive to the delivery of fruit-juice reward in association with rare stimuli in three monkeys tested. At cognition-enhancing doses, AF102B enlarged the amplitude of P300-like positivities in both monkeys tested; guanfacine enlarged the amplitude of P300-like positivities in one of two monkeys tested. These results add to existing evidence of human-like endogenous late positivities in monkeys that are influenced by the cholinergic and adrenergic systems, and suggest a possible role of m1 muscarinic and alpha-2A noradrenergic receptor subtypes.

Effects of guanfacine on three forms of distraction in the aging macaque.

alpha-2 adrenoceptor agonists, such as clonidine and guanfacine, enhance attention in aged animals. According to one theory, alpha-2 receptor agonists improve attention by decreasing distractibility to task-irrelevant stimuli. In two healthy aging bonnet macaques, we investigated the effects of low-(0.001 mg/kg) and high-dose (0.05 mg/kg) acute intramuscular guanfacine versus saline control on accuracy (number of trials correct) in three tasks requiring attention: delayed matching-to-sample, one-target visual tracking (test of focused attention) and two-target visual tracking (test of divided attention). Each task employed distracting stimuli in a different paradigmatic context. One monkey responded to guanfacine at both doses with significant rises in accuracy on all three tasks. The second monkey showed significant accuracy improvement for high-dose guanfacine only. No sedation was observed. These results suggest that guanfacine improves attention and reduces distractibility in multiple task contexts in healthy aging primates.

Development and testing of a five-item version of the Geriatric Depression Scale.

OBJECTIVE: To develop and test the effectiveness of a 5-item version of the Geriatric Depression Scale (GDS) in screening for depression in a frail community-dwelling older population. DESIGN: A cross-sectional study. SETTING: A geriatric outpatient clinic at the Sepulveda VA Medical Center, Sepulveda, California. PARTICIPANTS: A total of 74 frail outpatients (98.6% male, mean age 74.6) enrolled in an ongoing trial. MEASUREMENTS: Subjects had a comprehensive geriatric assessment that included a structured clinical evaluation for depression with geropsychiatric consultation. A 5-item version of the GDS was created from the 15-item GDS by selecting the items with the highest Pearson chi2 correlation with clinical diagnosis of depression. Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values were calculated for the 15-item GDS and the new 5-item scale. RESULTS: Subjects had a mean GDS score of 6.2 (range 0-15). Clinical evaluation found that 46% of subjects were depressed. The depressed and not depressed groups were similar with regard to demographics, mental status, educational level, and number of chronic medical conditions. Using clinical evaluation as the gold standard for depression, the 5-item GDS (compared with the 15-item GDS results shown in parentheses) had a sensitivity of .97 (.94), specificity of .85 (.83), positive predictive value of .85 (.82), negative predictive value of .97 (.94), and accuracy of .90 (.88) for predicting depression. Significant agreement was found between depression diagnosis and the 5-item GDS (kappa = 0.81). Multiple other short forms were tested, and are discussed. The mean administration times for the 5- and 15-item GDS were .9 and 2.7 minutes, respectively. CONCLUSIONS: The 5-item GDS was as effective as the 15-item GDS for depression screening in this population, with a marked reduction in administration time. If validated elsewhere, it may prove to be a preferred screening test for depression.

Divided attention-enhancing effects of AF102B and THA in aging monkeys.

The effects of cholinergic drugs proposed for treatment of cognitive impairment in normal aging and dementia on divided attention have been little studied in non-human primates. We tested the hypothesis that cholinergic drugs improve spatial divided attention in primates via a computer task requiring simultaneous tracking of two visual targets in three young and two aged healthy bonnet macaques. Task accuracy (number of correct responses) and reaction time (RT) were measured 2 h after administration of either the m1 agonist +/- -cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine (AF102B; 0.1-2.1 mg/kg IM) or the cholinesterase inhibitor 9-amino-1,2,3,4-tetrahydroamino-acridine (THA; 0.5-2.0 mg/kg orally). Accuracy increased for four of five monkeys at appropriate doses of one or both cholinomimetics, accompanied in two monkeys by a drop in RT. Responses were less uniform to THA than to AF102B. For the five-monkey group at Best dose, accuracy increased 34% (THA) or 43% (AF102B) above baseline (P<0.05 for both drugs), respectively, with no significant change in RT and with minimal untoward effects. Cholinotherapy may improve divided attention in young and aged healthy primates.

Reduction of motoric agitation and restlessness by AF102B and tacrine in the macaque.

The cholinesterase inhibitor tacrine (THA) and the M1 muscarinic agonist AF102B (cevimeline), both reported to enhance cognition in animals and humans, were tested in 5 macaques for reduction of spontaneous, random movements. Monkeys were videotaped 1 hour after administration of normal saline vehicle, after low- and high-dose intramuscular AF102B, and after low- and high-dose oral THA. Two independent blind judges counted numbers of spontaneous movements made by each monkey over 12 consecutive 15-second segments for each drug condition. Both THA and AF102B reduced movement significantly at high doses without overt side effects, warranting further research on the agitation-reducing potential of cognition-enhancing cholinomimetic drugs.

Effects of AF102B and tacrine on delayed match-to-sample in monkeys.

1. Object working memory, a function which declines in aging and dementia, was tested in young and aged pretrained monkeys using a delayed match-to-sample task. 2. During drug treatment, monkeys were given the m 1 muscarinic agonist AF102B (0.1-2.1 mg/kg i.m.), the cholinesterase inhibitor tacrine (0.5-2.0 mg/kg p.o.), or vehicle controls in a repeated measures design to assess putative cognitive enhancement. 3. Both agents improved task performance in both young and aged monkeys, AF102B yielding equivalent or greater, and less variable, improvement than tacrine. 4. AF102B may represent a low-toxicity alternative to tacrine for the treatment of age-related memory disorders.

The demented driver: the doctor's dilemma.

Physicians play an important role in the driver licensing process because drivers, most frequently older ones, acquire diseases that impact their ability to operate a motor vehicle safely and because patients, their families, and regulatory agencies rely on them for diagnosis and treatment. It is now fairly clear that moderately and severely demented patients cannot drive safely. However, the issue of whether the mildly or very mildly demented patient can drive safely has not been fully resolved, although substantial evidence is emerging that most of these individuals have a higher accident risk than their healthier aged counterparts. Physicians, most commonly primary care physicians, will be encountering growing numbers of aged driving persons, particularly those over 70, who are at the greatest risk for developing age-related brain diseases in addition to other physical ailments. It is now evident that the cognitive impairment that accompanies these conditions can have a dramatic impact on driving ability, and recent legislation in a growing number of states (e.g., California and Utah) requires physician reporting of cognitive impairment for driving purposes. Thus, what should the physician do with regard to the "at risk" older driver to ensure good medical practice while maintaining a sound ethical and legal posture toward the patient, his family, and the state and its agencies? This article reviews the status of physicians with regard to the cognitively impaired drivers, particularly in states where the law mandates reporting of such individuals. The problem of timely and effective screening for the cognitively impaired driver is raised, and alternative approaches to the screening process are discussed.

Effects of normal aging on the performance of motor-vehicle operational skills.

Operational skills involved in controlling a motor vehicle were measured in two groups of very healthy elderly drivers and a young control group to test the hypothesis that there are age-related declines in operational performance that may influence driver safety. An actual behind-the-wheel, standardized road test was employed using a motor vehicle equipped with sensors to record speed, braking activity, and lane position, as well as direction and magnitude of front-wheel and eye-movement excursions. The data from these sensors were used as dependent measures of operational performance. Older drivers made fewer steering and eye-movement excursions and drifted across the center line more frequently than the young control group. Younger drivers drove significantly faster and executed more braking applications than did their older counterparts. The motor-vehicle operational performance of older healthy drivers was related to visual-spatial attentional declines and the useful field of vision associated with the normal aging process.

Alzheimer and vascular dementias and driving. A prospective road and laboratory study.

OBJECTIVE: To characterize on-the-road, behind-the-wheel driving abilities and related laboratory performances of subjects with mild Alzheimer's disease (AD) and vascular dementia. DESIGN: Prospective, experimental study involving two mild dementia and three age and health control groups. Road test reliability and validity were assessed. SETTING: Greater western Los Angeles. Subjects were enrolled from the community by referral and from the Veterans Affairs dementia and diabetes clinics. PARTICIPANTS: Eighty-seven driving subjects were enrolled; 83 completed the study. A sample of eligible dementia clinic subjects consisting of 15 mild AD patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association probable AD criteria, while 12 met Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and Hachinski diagnostic criteria for multi-infarct dementia (vascular dementia). Clinic control subjects consisted of 15 age-matched patients with diabetes and without a history of stroke or dementia. Community controls consisted of 26 healthy, age-matched, older subjects (> 60 years) and 16 young subjects (20 to 35 years). MAIN OUTCOME MEASURES: Drive score from the Sepulveda (Calif) road test and laboratory measures of attention, perception, and memory. RESULTS: The drive scores in the mild AD group (mean, 22.1; SD, 3.8) and in the vascular dementia group (mean, 24.0; SD, 7.8) differed significantly (P < .001 studentized range test) from the drive scores in the diabetic control group (mean, 31.5; SD, 3.9), the older control group (mean, 32.6; SD, 2.8), and the young control group (mean, 33.6; SD, 3.2). Drive score among the three control groups did not vary significantly. Short-term memory (Sternberg), visual tracking, and Folstein Mini-Mental State Examination scores correlated best with drive score, with a cumulative R2 of 0.68. Drive score and number of collisions and moving violations per 1000 miles driven were negatively correlated (r = -0.38; P < .02). CONCLUSIONS: Based on this study, type and degree of cognitive impairment are better predictors of driving skills than age or medical diagnosis per se. Specific testing protocols for drivers with potential cognitive impairment may detect unsafe drivers more effectively than using age or medical diagnosis alone as criteria for license restriction or revocation.

Assessment of capacity to comply with medication regimens in older patients.

OBJECTIVE: To develop an instrument that will facilitate and focus the assessment of a patient's capacity to adhere to a medication regimen before its initiation. DESIGN: This is a crossectional study that compares medical inpatients and outpatients to an age-matched, community-living, independent and relatively healthy group on their ability to adequately understand and implement hypothetical but realistic medication regimens. SETTING: Department of Veterans Affairs Medical Center, Sepulveda, California. PARTICIPANTS: Fifty-five older subjects (65 years or older) were divided into three groups: (1) generally healthy comparisons (standard group) (n = 20); (2) medical outpatients (n = 15); and (3) medical inpatients ready for discharge (n = 20). MEASUREMENTS: Older subjects were first tested on their capacity to comply with a difficult medication regimen presented in scenario form. If scores on the first scenario did not meet a standard group-derived cutoff point, further testing was conducted with a simpler scenario to identify greater levels of impairment. RESULTS: The outpatient group had significantly lower scenario scores than did the healthy comparison group (P < .03). The simpler scenario also showed a trend toward outpatient impairment (P = .06). In the comparison group, only 5% failed Scenario 1, and none failed Scenario 2. The outpatient group had the most difficulty, with 40% failing Scenario 1 and one-third of those failing Scenario 2. This differed significantly from the comparison groups (Fisher's Exact P < .03). In the inpatient group 20% failed Scenario 1 and 75% of those failing Scenario 2. The sensitivity and specificity of the Folstein Mini-Mental State Examination in identifying scenario-impaired subjects were 73% and 80%, respectively. Question types were analyzed to determine which questions were most frequently missed. Memory and judgment questions were found overall to be the most frequently missed. Healthy controls missed some judgment questions; however, the outpatient group was significantly worse in this category (chi 2 = 5.08; P = .01). All three groups improved their scenario performance significantly with question cueing. CONCLUSION: A significant number of medically ill outpatients encountered difficulty in understanding or remembering correctly hypothetical but realistic medication regimens. This suggests that an older medical patient's cognitive and functional capacity to comply with medication regimens of differing complexity can be specifically assessed before the start of the regimen and probably should be assessed in patients whose compliance capacity is in question. The assessment instrument under development in this study may be helpful in detecting those who need assistance with medications, thus identifying the need for intervention before poor compliance can lead to increased morbidity, rehospitalization, and increased medical costs.