The influence of chronic stress on dementia-related diagnostic change in older adults.

Increased susceptibility of the aging brain to both chronic stress and incipient dementia-related neuropathology may accelerate cognitive decline. We investigated associations between chronic stress and diagnostic change in 62 individuals (mean age, 78.7 y) participating in an Alzheimer disease research center longitudinal study. The subjects, diagnosed at baseline as cognitively normal (CN) or with mild cognitive impairment (MCI), were followed for an average of 2.5 years. Senior neurologists, blind to detailed measures of stress and cognition, assigned diagnoses annually. Logistic regression analyses assessed the accuracy with which measures of stress (event-based ratings, cortisol levels) predicted the conversion to MCI and dementia. Eleven individuals with MCI at baseline received a dementia diagnosis during follow-up. Sixteen converted from cognitively normal to MCI. Prolonged, highly stressful experiences were associated with conversion from MCI to dementia. The cortisol awakening response, with age and education, was associated with a diagnostic change to MCI. Cortisol measures were not associated with the progression from MCI to dementia, and there was no association between stressful experiences and the change to MCI. Mechanisms associated with the transition from normal cognition to MCI may differ from those associated with a diagnostic change to dementia. These findings could facilitate the identification of interventional strategies to reduce the risk of decline at different stages of susceptibility.

The effects of prolonged stress and APOE genotype on memory and cortisol in older adults.

BACKGROUND: Chronic elevations in cortisol associated with prolonged stress have been associated with memory loss, as has the apolipoprotein E gene (APOE-epsilon4) genotype. Combined effects of stress and APOE status on memory and cortisol in humans have not been studied. METHODS: A semistructured interview with standardized scoring was used to measure stress level and univariate analysis of variance to assess effects of stress and APOE-epsilon4 status on memory and salivary cortisol in 91 nondemented subjects (mean age 78.8 years). RESULTS: Low-stress subjects performed better than high-stress subjects on delayed recall of stories (p = .04), word lists (p = .02), and visual designs (p = .04). APOE-epsilon4-negative subjects obtained better scores than epsilon4-positive subjects on immediate (p = < .01) and delayed (p < .01) recall of visual designs. Significant stress by APOE-epsilon4 interaction effects on memory (p = .03) and cortisol (p < .01) resulted from consistently worse memory and higher cortisol concentrations in the high stress, epsilon4-positive group. CONCLUSIONS: These findings are consistent with a model in which prolonged exposure of older, nondemented individuals to stress in the presence of an epsilon4 allele leads to memory decline. Further studies will assess whether stress and APOE-epsilon4 interact to increase the risk of developing Alzheimer's disease.

Development of a brief scale of everyday functioning in persons with serious mental illness.

We developed and tested the validity of a brief scale to assess everyday functioning in persons with serious mental illness. A sample of 434 adults with schizophrenia or schizoaffective disorder were administered the University of California, San Diego, Performance-Based Skills Assessment (UPSA), which assesses functional skills in 5 areas of life functioning (eg, finances and planning). Through use of factor analysis, we developed the UPSA-Brief, which consists of 2 subscales (communication and financial) from the original UPSA. UPSA-Brief scores were correlated with cognitive functioning, symptoms of psychosis, age, and education. We further tested the sensitivity and specificity of the UPSA-Brief for predicting residential independence using receiver-operating characteristic (ROC) curves. Finally, sensitivity to change was assessed through comparison of 2 interventions for improving UPSA-Brief scores. UPSA-Brief scores were highly correlated with scores on the full version of the UPSA (r = .91), with overall cognitive functioning (r = .57), and with negative symptoms (r = -.32). The discriminant validity of the UPSA-Brief was adequate (ROC area under the curve [AUC] = 0.73; 95% confidence interval [CI]: 0.67-0.78), with greatest dichotomization for the UPSA-Brief at a cutoff score of 60. The UPSA-Brief was significantly better than the Dementia Rating Scale, Positive and Negative Syndromes Scale positive, and Positive and Negative Syndromes Scale negative at predicting residential independence (all P values < .05). Participants receiving a behavioral intervention also improved significantly compared with a support condition (P = .023). The UPSA-Brief has adequate psychometric properties, predicts residential independence, is sensitive to change, and requires only 10-15 minutes to administer. Therefore, the UPSA-Brief may be a useful performance-based functional outcome scale.

Functional adaptation skills training (FAST): a randomized trial of a psychosocial intervention for middle-aged and older patients with chronic psychotic disorders.

OBJECTIVE: Behavioral interventions designed to improve functioning of older patients with schizophrenia and other chronic psychotic disorders have the potential to significantly increase patients' independence and quality of life. This study evaluated a psychosocial intervention designed to improve everyday living skills of middle-aged and older outpatients with chronic psychotic disorders. METHODS: A total of 240 patients with a DSM-IV-based chart diagnosis of schizophrenia or schizoaffective disorder participated in a 24-week, randomized controlled trial comparing a behavioral group intervention called "Functional Adaptations and Skills Training" (FAST; n=124) to a time-equivalent attention-control (AC; n=116) group focused on improving functional skills. RESULTS: Compared to participants randomized to AC, those in the FAST intervention demonstrated significant improvement in everyday living skills (p=.046) and social skills (p=.003), but not medication management skills (p=.268). CONCLUSIONS: Results suggest that middle-aged and older patients with psychotic disorders may benefit from participation in interventions designed specifically to improve functional skills.

Cognitive predictors of medication adherence among middle-aged and older outpatients with schizophrenia.

OBJECTIVE: Medication nonadherence presents a considerable problem in patients with schizophrenia. There are limited and conflicting data on the association of cognitive impairment with antipsychotic nonadherence. In this study, we evaluated the correlation of patients' scores on Mattis' Dementia Rating Scale (DRS; total and subscale scores) with scores on the Medication Management Ability Assessment (MMAA), a performance-based measure of medication management. METHODS: Participants included 110 outpatients with schizophrenia or schizoaffective disorder. Each was evaluated using the MMAA role-play tasks and the DRS. Patients also completed the Drug Attitude Inventory (DAI), and the PANSS (Positive And Negative Syndrome Scale). RESULTS: Age, DAI score, and DRS scores were all correlated with MMAA performance. In a stepwise regression analysis, only DRS scores were predictive of MMAA performance. Among the DRS subscales, conceptualization and memory were the best statistical predictors of MMAA performance. CONCLUSION: Cognitive functions, especially conceptualization and memory, were the strongest patient-related predictors of his or her ability to manage medications, over and above the effects of age, gender, education level, symptom severity, and attitudes toward medications. These results suggest a need for intervention studies focused on improving, or at least compensating for, specific cognitive deficits such as those in memory and conceptualization among patients with schizophrenia in order to improve their ability to manage medications.

Effects of chronic stress on memory decline in cognitively normal and mildly impaired older adults.

OBJECTIVE: The literature provides evidence of a strong relationship between greater stress and memory loss, but few studies have examined this relationship with both variables measured over time. The authors sought to determine the prospective association between subjective and objective measures of chronic stress and rate of memory decline in cognitively normal and mildly impaired older adults. METHOD: This longitudinal study was conducted at a university research center and included 61 cognitively normal subjects and 41 subjects with mild cognitive impairment (ages 65-97). Fifty-two subjects were followed for up to 3 years (mean=2 years) and received repeated stress and cognitive assessments. Exclusion criteria were dementia, significant medical or psychiatric conditions, and medication use (e.g., corticosteroids) that might affect cortisol level or cognitive functioning. The main outcome measure was a regression-based slope reflecting performance change on tests of global cognition and episodic memory as a function of baseline diagnosis, recent life events, and salivary cortisol. Examiners were blind to stress ratings and cortisol levels at the time of cognitive testing. RESULTS: Higher event-based stress ratings collected over the follow-up period were associated with faster cognitive decline in subjects with mild cognitive impairment but not in cognitively normal subjects. In contrast, higher cortisol levels were associated with slower cognitive decline in subjects with mild cognitive impairment but not in cognitively normal subjects. CONCLUSIONS: Chronic stress affects cognitive functioning differently in cognitively normal subjects and those with mild cognitive impairment. Cortisol, while likely to have neurotoxic effects over time, may enhance cognitive functioning in older adults compromised by existing cognitive deficits.

Functional adaptation skills training (FAST): a pilot psychosocial intervention study in middle-aged and older patients with chronic psychotic disorders.

OBJECTIVE: Developing behavioral interventions to improve functioning of older patients with schizophrenia and other chronic psychoses has the potential to significantly increase the patients' independence and quality of life. METHODS: The authors evaluated a psychosocial intervention designed to improve everyday living skills of middle-aged and older outpatients with very chronic psychotic disorders (mean duration of illness: 21 years). Forty patients who resided in board-and-care facilities were randomly assigned to either a 24-session functional adaptation skills training (FAST) group therapy program targeting problem areas identified in previous work as being problematic for this population (e.g., using public transportation) or treatment-as-usual. Almost all the participants also received antipsychotics. RESULTS: Compared with the patients randomized to the treatment-as-usual condition, FAST-treated patients' performance on everyday living skills improved significantly immediately post-intervention and was still significantly better at a 3-month maintenance follow-up period. There was no significant change in psychopathology. CONCLUSION: Results suggest that older patients with longstanding psychotic disorders may benefit from participation in this skills-training program.