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Biomedical subjects

C F Reynolds

Publications and source records attributed to C F Reynolds.

At least 253 records · Page 14Linked to original sources

Sleep stage physiology, mood, and vigilance responses to total sleep deprivation in healthy 80-year-olds and 20-year-olds.

Little is known about sleep and the effects of total sleep loss in the 'old old' (i.e., 80-year-olds). We investigated sleep, mood, and performance responses to acute sleep deprivation in healthy 80-year-olds (n = 10) and 20-year-olds (n = 14). The protocol consisted of three nights of baseline sleep, one night of total sleep deprivation, and two nights of recovery sleep. Mood and vigilance were tested using visual analog scales and a Mackworth clock procedure in the morning and evening of each study day. Daytime sleepiness was measured by five naps on the days following the third and sixth nights. Old subjects had lower sleep efficiency and less delta sleep than young subjects. However, sleep continuity and delta sleep were enhanced in both groups on the first recovery night, indicating that sleep changes in old subjects are at least partially reversible by this procedure. Surprisingly, young subjects had shorter daytime sleep latencies than the old, suggesting a greater unmet sleep need in the former group. Mood and performance were disturbed by sleep loss in both groups, but to a greater extent among the young. This suggests that acute total sleep loss is a more disruptive procedure for the young than for the old.

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Alzheimer's disease and depression: neuropsychological impairment and progression of the illness.

The authors longitudinally evaluated the cognitive functions of patients with probable Alzheimer's disease who also met criteria for major depression and compared them with matched patients with Alzheimer's disease who were not depressed. They found no significant difference in the pattern of neuropsychological deficits between the two groups; composite scores on attention, language, memory, learning, and visuospatial functions did not differentiate the two groups at baseline or at 1-year follow-up. The results of this preliminary report suggest that depression does not modify the neuropsychological features and the rate of progression of Alzheimer's disease.

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Reliability of NINCDS-ADRDA clinical criteria for the diagnosis of Alzheimer's disease.

Although the NINCDS-ADRDA Work Group has recently developed uniform clinical criteria for the diagnosis of Alzheimer's disease (AD), inter-rater reliability studies of these criteria are few. We report a study in which 2 neurologists and 2 psychiatrists independently reviewed clinical data abstracted from the records of 30 demented subjects and 10 nondemented control subjects participating in a longitudinal study of AD at the University of Pittsburgh. We recorded the clinical data on a standardized form; the subjects' identity and clinical and pathologic diagnoses were omitted. Each physician diagnosed each case according to the NINCDS-ADRDA criteria. We calculated the inter-rater agreement for all possible 2-way combinations of clinicians with the Kappa statistic, which ranged from 0.36 (fair agreement) to 0.65 (substantial agreement). We conclude that current NINCDS-ADRDA criteria enable moderate levels of agreement among clinicians in general.

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EEG findings in depressive pseudodementia and dementia with secondary depression.

We report EEG findings in 33 elderly patients with mixed symptoms of depression and dementia, followed longitudinally to confirm diagnosis. Two groups of patients, dementia with depressive features (mixed-DEM, group I, n = 23) and patients with depressive pseudodementia (mixed-DEP, group II, n = 10), were defined. In addition, we also included, for comparison purposes, 35 patients with probable AD without depressive features (group III), 23 patients with major depression without cognitive impairment (group IV), and 61 healthy elderly controls (group V). We found significant group differences on waking EEGs between those mixed patients who did well after treatment for depression (depressive pseudodementia) compared to patients having dementia with secondary depression. The differences paralleled those between the 'pure' groups of demented and depressed patients. In patients with either depression or depressive pseudodementia, the EEG was usually normal or showed only mild abnormalities. In contrast, the majority of patients with either dementia or dementia with secondary depression had abnormal EEGs, with approximately one-third having moderate (or severe) abnormalities. Although the EEG was usually normal or only mildly abnormal in patients with pseudodementia or depression, these groups (II and IV) did show a significant slowing of the dominant posterior rhythm compared to controls. They also had a higher percentage of generalized abnormal EEGs than controls and this difference was significant between group IV (depression) and controls.

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Comparison of EEG sleep measures among depressive subtypes and controls in older individuals.

Psychobiological research has been used to validate subtypes of affective disorder. Nosologic separation of delusional from nondelusional depression has recently been aided by sophisticated analyses of sleep electrophysiology. In the present study, the sleep of elderly delusional and nondelusional depressed patients could be successfully distinguished from that of aged controls using standard sleep parameters. However, only a combination of manual and spectral analytic techniques separated the depressive subtypes. These results are preliminary and need replication in a larger sample.

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The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research.

Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.

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Open-trial maintenance pharmacotherapy in late-life depression: survival analysis.

We report preliminary findings from an ongoing, open trial of maintenance nortriptyline pharmacotherapy in 27 elderly depressed patients (median trial length: 18 months). While patients were on maintenance nortriptyline (mean dose: 50 mg/day) with steady-state plasma levels in the range of 50-150 ng/ml, 58% of Q-6 monthly ratings on the Hamilton Rating Scale for Depression have been 10 or lower, Folstein Mini-Mental State ratings have remained above 27, and a minimal level of side effects with no increase over time has been observed. Four of 27 patients (14.8%) have suffered recurrences and have required rehospitalization at 6, 9, 10, and 13 months. Survival analysis showed an 85% survival rate (without recurrence) at 12 months and 81.5% at 18 months. Mean survival time without recurrence is 21.3 months to date. Although our pilot experience with maintenance nortriptyline in late-life depression appears more favorable than outcomes reported in earlier naturalistic studies (where no attempt was made to keep patients in systematic maintenance therapy), the need for controlled studies of maintenance therapies in late-life depression is nonetheless underscored by the current data and other naturalistic data from the United Kingdom.

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Electroencephalographic sleep in late-life neuropsychiatric disorders.

Late-life depression and dementia of the Alzheimer's type both have profound, although different, effects on electroencephalographic (EEG) sleep patterns. Thus, while depression is associated with REM sleep disinhibition and extreme sleep fragmentation (e.g., sleep onset REM periods and early morning awakenings), Alzheimer's disease is associated with deficits in the production of phasic activity during sleep (e.g., rapid eye movements and K-complexes) and with increased rates of sleep-disordered breathing. These differences have been shown to be reliable in large numbers of patients during the past five years and appear to extend to differences in sleep between depressive pseudodementia and dementia with secondary depression. Preliminary data also suggest that pretreatment sleep onset REM periods may be associated with enhanced vulnerability to recurrent depression. In summary, sleep physiological measures provide useful diagnostic and prognostic indexes in late-life neuropsychiatric disorders.

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Clinical significance of sleep-disordered breathing in Alzheimer's disease. Preliminary data.

In a study of 15 probable Alzheimer's patients and 12 healthy elderly control subjects, Alzheimer's patients had a significantly higher apnea index (patients versus controls, mean +/- SD: 6.3 +/- 6.6 vs 1.8 +/- 2.7, P less than .05) and greater maximal duration of apnea (patients versus controls, median: 50.0 vs 28.5 seconds, P less than .001), but no significant increase in oxyhemoglobin desaturation compared with controls. (The accepted normal threshold for abnormality is an apnea index more than 5.) Although three of seven psychometric tests (odd-even, category retrieval, face-hand test) showed diurnal effects on one or more of their subscores, with Alzheimer's patients having significantly poorer scores at the AM than at PM testing, overnight change scores in the psychometric tests were not significantly correlated with severity of sleep-disordered breathing. Further, only 18.1% of the disruptive (ie, requiring intervention) nocturnal behaviors of the Alzheimer's patients were temporally linked to sleep-disordered breathing. The current data suggest that sleep-disordered breathing in nonmedicated Alzheimer's patients is relatively mild and is not a predictor of either overnight mental status changes, of disruptive nocturnal behaviors, or of daytime behavioral fluctuations. Additional studies of more severely demented patients and possibly of sleeping pill effects would be useful in further evaluating the role of sleep apnea in Alzheimer behavioral changes.

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Breathing during wakefulness and sleep after human heart-lung transplantation.

To study the effects of pulmonary denervation on breathing during sleep, sleep studies were conducted on seven heart-lung transplant recipients (H-LT) and a comparable number of sex-matched normal subjects of similar age. Four of the H-LT patients had a restrictive pattern on spirometry. The time since transplantation ranged from 45 to 1,102 days. There were no significant differences between the groups with respect to total sleep time or distribution of sleep stages. There were no significant differences between the H-LT recipients and normal subjects with respect to baseline awake oxyhemoglobin saturation (SaO2) or the nadirs of SaO2 during REM and non-REM sleep, the absolute number and frequency (number per hour of sleep) of apneas, hypopneas, desaturation events, both over the whole night of study or separately during non-REM and REM sleep. Across wakefulness and all sleep stages, the H-LT patients tended to have shorter total respiratory cycle times (Ttot) (p = 0.052) and more rapid breathing frequency (F) than the normal subjects. This was associated with significantly shorter inspiratory times (Tl) (p less than 0.001) and smaller duty cycles (Tl/Ttot) (p less than 0.005) in the H-LT recipients. During non-REM and REM sleep, F tended to be higher in the H-LT recipients with pulmonary restriction than in the nonrestricted patients. There were no significant differences between the H-LT recipients and the normal subjects with regard to the periodicity of breathing, either in terms of timing parameters or breath amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

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Predicting mortality in mixed depression and dementia using EEG sleep variables.

The authors report a study of electroencephalographic (EEG) sleep predictors of two-year mortality in 26 elderly patients with mixed symptoms of depression and cognitive impairment. Patients who had died by two-year follow-up were characterized by significantly longer rapid eye movement (REM) sleep latencies at baseline, less robust REM sleep rebound following all-night sleep deprivation, and baseline apnea-hypopnea indexes greater than 3. Logistic regression analysis using the apnea-hypopnea index value and REM latency correctly predicted 77% of survivors and non-survivors. Survival time following initial measurements was significantly correlated with REM sleep time (r = 0.78, p less than .02) and duration of first REM sleep period (r = 0.75, p less than .02). The authors speculate that changes in these predictor variables may indicate impairment in the cholinergic control of cognitive function, REM sleep, and respiratory function.

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Biologic markers in borderline personality disorder: a review.

The use of biologic markers in the evaluation of borderline personality disorder (BPD) patients is reviewed. Many patients with Axis II BPD have coexisting Axis I diagnoses of which depression is the most commonly reported. Biologic markers have not aided in the diagnosis of BPD, but some markers, particularly EEG sleep, are not only abnormal in BPD, but also appear to discriminate Axis I depression from other Axis I codiagnoses. Monoamine oxidase, in vitro red blood cell lithium ratio, and P300 auditory evoked potential when used alone or in a combined diagnostic approach, show promise in identifying these codiagnoses as well. Dexamethasone suppression and thyrotropin-releasing hormone tests appear nonspecific in this population. Pharmacologic trials have demonstrated that some BPD patients have good therapeutic response to antipsychotics and tranylcypromine and poor response to alprazolam.

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Sleep and depression in late life.

Depression is one of the most serious and prevalent neuropsychiatric disorders of old age. Despite its prevalence, depression in the aged is frequently unrecognized or is misdiagnosed. This article reviews the existing knowledge of several sleep-related areas and discusses possible future studies into sleep as a prognostic indicator for recurrent and bereavement-related depressions in late life.

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Nocturnal penile tumescence in healthy 20- to 59-year-olds: a revisit.

This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 healthy men aged 20-59 years, without complaints of erectile dysfunction. In general, the current measures show good concordance with those reported by Karacan and colleagues in 1976. The effect of "pathology-free" aging (from age 20 to 59) on electrographic measures of NPT is relatively modest, accounting for 8.4-14.4% of the variance. Furthermore, no age effect on visual estimates of erectile fullness or on buckling force estimates of penile rigidity were present. Maximum buckling force and maximum erectile fullness showed stability across the four decades of the Pittsburgh sample.

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