Dimensions of physical frailty and cognitive function in older adults with amnestic mild cognitive impairment.

OBJECTIVE: The objective of this study was to examine relationships between dimensions of physical frailty and severity of cognitive impairment in older adults with amnestic mild cognitive impairment (aMCI). PATIENTS AND METHODS: The prevalence of physical frailty dimensions including slow gait speed, low physical activity, and low grip strength was examined among 201 sedentary older adults with aMCI. Associations between dimensions of physical frailty and severity of cognitive impairment, as measured with the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and individual dimensions of cognitive function were examined using multiple linear regression models. RESULTS: Greater than 50% of participants met physical frailty criteria on dimensions of slow gait speed, low physical activity and low grip strength. Slower gait speed was associated with elevated severity of cognitive impairment. Both gait speed and physical activity were associated with individual dimensions cognitive function. CONCLUSIONS: Dimensions of physical frailty, particularly gait speed, were associated with severity of cognitive impairment, after adjusting for age, sex and age-related factors. Further studies are needed to investigate mechanisms and early intervention strategies that assist older adults with aMCI to maintain function and independence.

Exercise interventions for dementia and cognitive impairment: the Seattle Protocols.

Research evidence strongly suggests that increased physical exercise may not only improve physical function in older adults but may also improve mood and slow the progression of cognitive decline. This paper describes a series of evidence-based interventions grounded in social-learning and gerontological theory that were designed to increase physical activity in persons with dementia and mild cognitive impairment. These programs, part of a collective termed the Seattle Protocols, are systematic, evidence-based approaches that are unique 1) in their focus on the importance of making regular exercise a pleasant activity, and 2) in teaching both cognitively impaired participants and their caregivers behavioral and problem-solving strategies for successfully establishing and maintaining realistic and pleasant exercise goals. While additional research is needed, initial findings from randomized controlled clinical trials are quite promising and suggest that the Seattle Protocols are both feasible and beneficial for community-residing individuals with a range of cognitive abilities and impairments.

Head circumference and incident Alzheimer's disease: modification by apolipoprotein E.

BACKGROUND: The clinical expression of AD likely occurs when the accumulation of degeneration in specific brain regions leads to the descent below a critical threshold of "brain reserve" beyond which normal cognitive function cannot be maintained. The association between head circumference (HC), a measure of brain reserve, and the incidence of probable AD was examined in a large nondemented cohort that has been followed since 1992 and its modification by APOE epsilon 4 genotype. METHODS: Fifty-nine incident cases of probable AD were identified from 1,869 initially nondemented individuals seen at the baseline examination (1992 to 1994) and followed for a mean of 3.8 years. Variables measured at baseline included age, education, gender, HC, height, weight, and score on the National Adult Reading Test-Revised. APOE was genotyped at the time of the first biennial examination (1994 to 1996) and was available for 1,111 individuals in the cohort. Cox proportional hazard regression was performed to estimate hazard ratios (HR) for probable AD for HC and other covariates. RESULTS: Incident cases were significantly older, less educated, shorter, and lighter, had lower estimated verbal IQ scores, and were more likely to have at least one APOE epsilon 4 allele than unaffected individuals. The HR associated with the lowest tertile of HC (<21.4 inches) adjusted for education, gender, and APOE epsilon 4 was 2.3 (95% CI 0.7 to 6.9, p = 0.16). The HR for one or two APOE epsilon 4 alleles was significant (HR = 4.8, 95% CI 1.8 to 12.9, p = 0.002). The combination of low HC and APOE epsilon 4 strongly predicted earlier onset of AD with HR = 14.1 (95% CI 3.0 to 65, p = 0.0007). CONCLUSIONS: Smaller HC, in the presence of the APOE epsilon 4 allele, hastens the age at onset of AD. These results support the brain reserve hypothesis and its importance in precipitating the clinical expression of AD among genetically predisposed individuals.

Alcohol, aging, and cognitive performance in a cohort of Japanese Americans aged 65 and older: the Kame project.

OBJECTIVE: To investigate the effects of light to moderate alcohol consumption on cognitive performance. DESIGN AND SETTING: A cross-sectional analysis including older Japanese Americans in King County, WA, enrolled in the Kame Project, a population-based study of cognition, dementia, and aging. PARTICIPANTS: 1,836 cognitively intact participants aged 65 and older who participated in the baseline (1992-1994) examination. MEASUREMENT: Cognitive performance was measured using the Cognitive Abilities Screening Instrument, reaction time (simple and choice), and a measure of vocabulary (North American Adult Reading Test). RESULTS: Multivariate analyses were used to examine the relationship between cognitive performance and alcohol consumption at baseline with men and women together and then separately controlling for age, education, smoking, history of stroke, angina, hypertension, diabetes, and coronary heart disease. Findings showed lower cognitive test scores were observed for men who were either abstainers or in the heavy drinking group. For women, a linear relationship between alcohol consumption and cognitive performance was seen on two of the four measures of cognitive functioning. No significant difference in the association of drinking and cognitive function was identified within the different Japanese American subgroups. CONCLUSION: RESULTS suggest a possible positive relationship between light to moderate drinking and cognitive performance in an aging Japanese American population. Additional long-term prospective and cross-cultural studies are needed to determine the generalizability of these findings to other aging cohorts.

Anxiety and Alzheimer's disease.

This study investigated symptoms of anxiety in two samples of clinic outpatients diagnosed with Alzheimer's disease (AD). Clinician and caregiver reports were obtained using standardized measures to characterize a broad array of anxiety symptoms. Anxiety symptoms were reported for a substantial proportion of subjects, regardless of whether clinician or caregiver ratings were used. Anxious or worried appearance was most common (68% to 71%), followed by fearfulness, tension, restlessness, and fidgeting (37% to 57%). Sleep disturbance and various somatic symptoms were less common (8% to 34%). Although anxiety symptoms were prevalent, only 5% to 6% of subjects met Diagnostic and Statistical Manual of Mental Disorders criteria for the diagnosis of generalized anxiety disorder. In both samples, anxiety symptoms were associated with depression, behavioral disturbances, and increased cognitive impairment. Study findings support a high occurrence of anxiety in patients with dementia, and treatments for anxiety might therefore be helpful in reducing the psychiatric burden of AD.

Ethnicity and cognitive performance among older African Americans, Japanese Americans, and Caucasians: the role of education.

This cross-sectional analysis evaluated the association between ethnicity and cognitive performance and determined whether education modifies this association for nondemented older people (103 African Americans, 1,388 Japanese Americans, 2,306 Caucasians) in a study of dementia incidence. African Americans scored lower (median 89 out of 100) than Japanese Americans (93) and Caucasians (94) on the Cognitive Abilities Screening Instrument (CASI). Education affected CA

Neuropsychological test performance in a cognitively intact sample of older Japanese American adults.

The purpose of this paper was to present population-based data showing the effects of age on cognitive test performance in a sample of older Japanese American adults. In addition, the relative effects of education, gender, and primary spoken language were compared to effects that have been reported in the literature for majority culture older adults. Subjects included 201 non-demented Japanese American adults age 70 and older currently enrolled in the Kame Project, a prospective study of aging and dementia in King County, WA. Cognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological assessment battery, WAIS-R Digit Span and Digit Symbol subtests, Trail Making Test, Purdue Pegboard, and Finger Tapping. Older age was associated with significantly (p<0.05) lower scores on all tests; less than high school education was associated with lower scores on all tests except Digit Span, Finger Tapping, and the Purdue Pegboard. Women and English-speaking participants scored higher than men and Japanese speakers on various tests of memory, attention, and visuomotor ability. These data reinforce the importance of using appropriately corrected norms when interpreting results of cognitive screening tests with minority culture older adults.

Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women: The Kame Project.

BACKGROUND: The relation between estrogen and cognition among postmenopausal women remains controversial. Also uncertain is whether the proposed association varies between women taking unopposed estrogen and those taking estrogen combined with progestin. OBJECTIVE: To determine whether unopposed estrogen and combined estrogen-progestin use were associated with the rate of cognitive change in a cohort of older, Japanese American, postmenopausal women. METHODS: A prospective observational study in a population-based cohort of older Japanese Americans (aged > or =65 years) living in King County, Washington. Cognitive performance was measured in 837 women at baseline (1992-1994) and 2-year follow-up (1994-1997) examinations using the 100-point Cognitive Abilities Screening Instrument (CASI). Least squares means general linear models were used to estimate the 2-year rate of cognitive change according to categories of postmenopausal estrogen use. RESULTS: Approximately half of this cohort (n=455) had never used estrogen at any time since menopause, 186 were past users, 132 were current unopposed estrogen users, and 64 were current estrogen-progestin users. The majority of current estrogen users were taking conjugated estrogens, and all women receiving combined therapy were taking medroxyprogesterone acetate. After adjusting for age, education, language spoken at the interview, surgical menopause, and baseline CASI score, women who had never used postmenopausal estrogen improved slightly on the CASI scale (mean adjusted change, 0.79; SEM, 0.19). This change was significantly greater for current unopposed estrogen users (mean adjusted change, 1.68; SEM, 0.36; P=.04) and significantly worse for current estrogen-progestin users (mean adjusted change, -0.41; SEM, 0.50; P =.02) compared with never users. The improvement observed in past users (mean adjusted change, 1.12; SEM, 0.29) was intermediate between the changes for never users and current unopposed estrogen users and not significantly greater than that for never users (P=.35). CONCLUSIONS: Our findings support a modest beneficial association between current unopposed estrogen use and the rate of cognitive change. We also observed a modest detrimental association between current estrogen-progestin use and the rate of cognitive change. The clinical significance of these modest differences, however, is uncertain. Data from large, long-term randomized trials are required before applying this information to the clinical setting.

The cognitive abilities screening instrument (CASI): data from a cohort of 2524 cognitively intact elderly.

OBJECTIVES: To describe the effects of age and education for the Cognitive Abilities Screening Instrument (CASI), a 25-item test of cognitive function. DESIGN: Cross-sectional descriptive study of the initial enrollment in a community-based prospective cohort study. PARTICIPANTS: A total of 2524 cognitively intact older adults over age 65 who were members of a major health maintenance organization, and who consented to participate in a longitudinal study. MEASUREMENTS: Summary scores for the CASI are given in the form of mean, median and percentile distributions specific for age and educational level. RESULTS: Based upon maximum likelihood analyses, age and education were significant (p<0.0001) predictors of total CASI score. Increased age and lower education were associated with a lower CASI score, as well as an increased spread in score distribution. Gender was also significantly related (p<0.01) to total CASI, with women having a slightly higher distribution of scores. Mean total scores ranged from CASI=82.2 (SD=9.0) in subjects aged 90-95 who had less than a high school degree to CASI=94.8 (SD=3. 8) in subjects aged 65-69 with at least a high school education. CONCLUSIONS: Like most cognitive screening instruments, performance on the CASI in non-demented persons is influenced by age and education. The reference values for 5-year age categories described in this article should be useful for clinicians and research investigators when using the CASI as a measure of cognitive function.

Impaired olfaction as a marker for cognitive decline: interaction with apolipoprotein E epsilon4 status.

OBJECTIVE: To determine whether olfactory status predicts cognitive decline (CD) over a 2-year follow-up period. METHODS: The authors enrolled individuals in a community-based longitudinal study of memory and aging in the Japanese-American community in King County, WA, between 1992 and 1994. At baseline they screened 1,985 persons using the Cognitive Abilities Screening Instrument (CASI) and the 12-item Cross-Cultural Smell Identification Test (CC-SIT). Of these 1,985 people, 1,836 were found not to be demented. Two years later the authors rescreened 1,604 participants with the CASI. They defined CD as a 2-year loss of > or =5.15 points/100 on the CASI. They genotyped 69% of the 1,604 people completing both examinations for apolipoprotein E (apoE). RESULTS: After adjusting for age, CASI score at baseline, education, smoking, sex, and follow-up time, the authors determined an odds ratio (OR) for CD of 0.90 (95% CI, 0.84 to 0.97) for an increase in each correct point on the CC-SIT (range, 0 to 12). Compared with normosmics, the OR for persons with impaired olfaction (microsmics) was 1.25 (95% CI, 0.83 to 1.89) and for anosmics the OR was 1.92 (95% CI, 1.06 to 3.47). Persons who were anosmic at baseline and who had at least one APOE-epsilon4 allele had 4.9 times the risk of CD (95% CI, 1.6 to 14.9) compared with normosmics without the epsilon4 allele. The estimated relative risk among women was 9.7 (95% CI, 1.3 to 70.4), and for men the risk was 3.2 (95% CI, 0.8 to 12.6). Receiver operating characteristic (ROC) curves showed that although the area under the curve (AUC) for baseline CASI was only 0.51, the AUC for CC-SIT alone was 0.62. Adding CC-SIT to the ROC model with CASI improved the AUC curve from 0.51 to 0.62. CONCLUSIONS: Unexplained olfactory dysfunction in the presence of one or more APOE-epsilon4 alleles is associated with a high risk of cognitive decline. Cross-Cultural Smell Identification Test classifies people with cognitive decline correctly to a greater degree than a global cognitive test.

Characteristics of sleep disturbance in community-dwelling Alzheimer's disease patients.

This study examined the frequency, predictors, and impact of sleep problems in a population-based sample of 205 Alzheimer's disease (AD) patients. Sleeping more than usual and early morning awakenings were the most common sleep problems reported but were the least disturbing behaviors for caregivers. Night-time awakenings were less common but were most disturbing to caregivers. Using logistic regression analyses, the factors most strongly associated with night awakenings among patients were male gender, greater memory problems, and decreased functional status. Patient depression increased the risk for caregivers to rate patient sleep problems as more disturbing overall. Cluster analyses revealed three characteristic groups of patients who awakened caregivers: one group was inactive during the day but had few other behavior problems; one group had increased levels of fearfulness, fidgeting, and occasional sadness; and the third group had multiple behavior problems, including frequent episodes of sadness, fearfulness, inactivity, fidgeting, and hallucinations. These findings indicate that the nature of sleep problems in AD is multifaceted; future research on the occurrence and treatment of sleep disturbance in dementia patients should consider the patterns of individual differences that may influence its development.

Anxiety of Alzheimer's disease: prevalence, and comorbidity.

BACKGROUND: Anxiety may be associated with psychiatric morbidity, disability, increased health care utilization, and mortality in Alzheimer's disease (AD) patients as it is in the general adult population. However, the phenomenology of anxiety symptoms in AD and its relationship to dementia progression, comorbid depression, and the presence of other problematic behaviors have not yet been examined. METHOD: Data on anxiety symptoms and their coexistence with other factors were obtained in 523 community-dwelling AD patients through interviews with their caregivers and direct physical examination. The prevalence of anxiety symptoms and their association to patient depression, other behavioral problems, gender, and age was investigated. RESULTS: Anxiety symptoms were common, occurring in 70% of subjects. Anxiety symptoms were significantly correlated with ADL impairment and other behavioral disturbances, including wandering, sexual misconduct, hallucinations, verbal threats, and physical abuse. Comorbidity of anxiety-depression was also prevalent: 54% of the sample had both anxiety and depression symptoms. ADL impairment and problem behaviors were significantly associated with comorbidity; however, the latter association was explained entirely by the presence of anxiety. CONCLUSION: Anxiety symptoms were common and significantly related to ADL and additional neuropsychiatric problems in this sample. These results indicate the need for additional research into the phenomenology of anxiety and comorbid anxiety-depression in AD and for the development and investigation of effective assessment and treatment of anxiety in AD clinical practice.

Cognitive decline and Japanese culture in a cohort of older Japanese Americans in King County, WA: the Kame Project.

OBJECTIVES: The prevalence of Alzheimer's disease in studies of Japanese show generally lower rates when compared with those of Caucasians. We hypothesized that among a cohort of Japanese Americans lifestyle differences would act to modify progression of the Alzheimer pathologic process over many years, resulting in a slower cognitive decline among persons whose lifestyle is more characteristically Japanese. METHODS: One thousand, eight hundred and thirty-six nondemented persons were screened with the Cognitive Abilities Screening Instrument (CASI) at baseline, and 1,604 were rescreened 2 years later. Baseline questions included migration status, exposure to Japanese culture in early life and maintenance of such culture in adulthood, and other risk factors. Cognitive decline was defined as a 2-year loss of > or = 5.15 points/100 on CASI. RESULTS: In multivariable logistic regression, variables relating to reading, writing, and speaking Japanese, being born or having lived in Japan in early life, and having friends who are only/mostly Japanese were inversely associated with cognitive decline (odds ratios ranged between 0.28 and 0.64, with p < .05). Two factors emerged in a factor analysis of these variables. The strongest explained 49% of the variance for acculturation and loaded heavily on knowledge of the Japanese language and having spent one's early years in Japan. When this factor was dichotomized into the top 20th percentile, it predicted cognitive decline with an odds ratio of 0.12 (95% CI 0.03-0.49). DISCUSSION: These results show that a Japanese lifestyle may decrease the risk of expressing cognitive decline over a 2-year follow-up period. Lower cardiovascular disease rates among Japanese may also predispose them to lower rates of cognitive decline. The greater social support characteristic of Japanese culture as well as the role that Japanese language and culture may play in neural connectivity during brain development and/or in mental stimulation in adult life may also explain our findings.

Wandering: a significant problem among community-residing individuals with Alzheimer's disease.

This study evaluated the frequency, predictors, and effects of wandering in a population-based sample of 193 individuals with Alzheimer's disease (AD). Although wandering occurred in subjects at all levels of cognitive impairment, analysis of variance indicated that for the group as a whole, greater frequency of wandering was associated with significantly more impairment in cognition, day-to-day functioning, and behavior. Caregiver distress also increased significantly with increased frequency of wandering. Logistic regression modeling identified functional impairment and disruptive behavior problems as the strongest independent predictors of wandering occurring within the past week. Cluster analysis revealed four characteristic groups of wanderers that represented a continuum of wandering frequency, each having a unique pattern of other behavioral disturbances. Based on this analysis, we recommend further evaluation and the development of possible treatment strategies that address the individual differences found among AD patients who wander.

Successful behavioral treatment for reported sleep problems in elderly caregivers of dementia patients: a controlled study.

Although sleep problems are common among dementia caregivers, there has been no research thus far describing treatment of such problems using behavioral techniques. In this study, 36 elderly dementia caregivers with disturbed sleep were randomly assigned to either a brief behavioral intervention or a wait list control. The active treatment consisted of standard sleep hygiene, stimulus control, and sleep compression strategies as well as education about community resources, stress management, and techniques to reduce patient disruptive behaviors. Caregivers in active treatment showed significant improvements in sleep at post-treatment and 3-month follow up. No significant differences between groups were observed for caregiver mood, burden, or patient behavior problems, suggesting that sleep improvements were not an artifact of depression treatment. Treatment responders tended to be younger and more compliant with treatment recommendations than non-responders. Results suggest that behavioral techniques may well be a viable alternative to medication for sleep problems in aging caregivers.

Standardization of the clinical diagnosis of the dementia syndrome and its subtypes in a cross-national study: the Ni-Hon-Sea experience.

BACKGROUND: Clinical investigators from Seattle, Honolulu, Tokyo, and Hiroshima participated in two standardization exercises in which data were collected on independent assessments. Exercises were conducted to evaluate the interobserver agreement on clinical diagnoses of dementia and dementia subtypes in a cross-national study of dementia prevalence and incidence rates in the United States and Japan. METHOD: Fifteen clinicians from four participating sites assessed the diagnosis of 85 patients based on standardized summaries of clinical and diagnostic test data on each patient. Diagnostic guidelines and conventions were adopted on the basis of group consensus during standardization exercises. RESULTS: Using DSM-III-R criteria, generally good levels of agreement for all dementia diagnostic categories occurred in both years. For most measures of diagnostic agreement, improvements were observed between the 1995 and 1996 standardization sessions. Interrater agreement was highest for discrimination between dementia and nondementia (1996 overall kappa, K = .90). The kappa values for dementia subtypes in 1996 ranged from .5 to .85, and for all sites combined the value was .67. For dementia subtypes, percent agreement was highest for vascular dementia and Alzheimer's disease, but was less reliable for other types of dementia. CONCLUSIONS: Clinicians from different cultures and medical traditions can reliably use the DSM-III-R criteria to classify dementia cases in cross-national research. The interrater agreement on dementia and its subtypes improved after clear-cut guidelines for interpretation of diagnostic criteria were developed and followed.

Exercise and activity level in Alzheimer's disease: a potential treatment focus.

This article provides information on the baseline health and physical function of 30 individuals with Alzheimer's disease (AD); describes a community-based program designed to increase balance, flexibility, strength, and endurance in these persons by the training of caregivers to facilitate and supervise exercise activity; and documents the adherence of these subjects and their caregivers to this intervention. Subjects were recruited from an ongoing, community-based Alzheimer's Disease Patient Registry, and met NINCDS-ADRDA criteria for probable or possible AD. Caregivers were family members living with the demented individuals in the community. Physical performance was measured using walking speed, functional reach, and standing balance. Health status was measured with the Medical Outcomes Study Short Form, the Sickness Impact Profile, and caregiver reports of subject's restricted activity days, bed disability days, falls, and exercise participation. Baseline data indicated that persons with AD were impaired on measures of physical performance and function, compared to published data on nondemented older adults. During a 12-wk treatment period, caregivers were taught to guide their demented charges in an individualized program of endurance activities (primarily walking), strength training, and balance and flexibility exercises. Adherence data indicated that 100% of the subjects were compliant with some exercise recommendations, and one-third completed all assigned exercises during the training period. Caregivers were able to learn and direct subjects during scheduled exercise activities. These findings indicate that the integration of exercise training into the care of persons with AD is both needed and feasible. Further research is currently underway to determine the efficacy of this approach for reducing additional physical disability in these individuals.

Memory, thinking, and aging. What we know about what we know.

Cognition is the foundation that underlies all daily activities, from the most basic to the most complex. Successful aging depends, in large part, on maintaining a level of cognitive ability that allows a person to interact effectively and appropriately with the environment. In the following article we provide an overview of the effects of aging on cognition; discuss physical, social, and psychological factors that have been shown to influence cognition in old age; and review current literature on interventions that may optimize successful cognitive aging. We conclude with a discussion of abnormal cognitive aging and review current research on risk factors and treatments of Alzheimer's disease and other dementing illnesses.

Estrogen replacement therapy and cognitive function in postmenopausal women without dementia.

The epidemiologic evidence for an association between estrogen and cognitive function among healthy postmenopausal women remains controversial. Equivocal findings may be explained, in part, by differences in the methodologic approaches of these studies. Overall, the evidence for a positive relationship comes primarily from randomized clinical trials. These trials suggest an acute effect on specific tests of recent verbal memory and tasks incorporating concept formation and reasoning. The potential long-term effects of estrogen in slowing or delaying the age-related decline in cognitive function require further study. More data are needed to determine the effects of estrogen replacement therapy on cognitive function, independent of changes in mood and depressive symptoms. In addition, evidence suggests that progesterone may mitigate the beneficial effects of estrogen on mood. Research should be undertaken to determine the interactive effects of estrogen and progesterone on cognitive function. Lastly, there should be continued investigation by both epidemiologic and basic neuroscientific studies to further elucidate the specific cognitive domains that may respond to estrogen.