Prefrontal hypoactivation during working memory in bipolar II depression.

BACKGROUND: Patterns of abnormal neural activation have been observed during working memory tasks in bipolar I depression, yet the neural changes associated with bipolar II depression have yet to be explored. METHOD: An n-back working memory task was administered during a 3T functional magnetic resonance imaging scan in age- and gender-matched groups of 19 unmedicated, bipolar II depressed subjects and 19 healthy comparison subjects. Whole-brain and region-of-interest analyses were performed to determine regions of differential activation across memory-load conditions (0-, 1- and 2-back). RESULTS: Accuracy for all subjects decreased with higher memory load, but there was no significant group × memory load interaction. Random-effects analyses of memory load indicated that subjects with bipolar II depression exhibited significantly less activation than healthy subjects in left hemispheric regions of the middle frontal gyrus [Brodmann area (BA) 11], superior frontal gyrus (BA 10), inferior parietal lobule (BA 40), middle temporal gyrus (BA 39) and bilateral occipital regions. There was no evidence of differential activation related to increasing memory load in the dorsolateral prefrontal or anterior cingulate cortex. CONCLUSIONS: Bipolar II depression is associated with hypoactivation of the left medio-frontal and parietal cortex during working memory performance. Our findings suggest that bipolar II depression is associated with disruption of the fronto-parietal circuit that is engaged in working memory tasks, which is a finding reported across bipolar subtypes and mood states.

The DrivingHealth® Inventory as a clinical screening tool-assessment of face validity and acceptance.

To investigate the use and potential for patient acceptance of the DrivingHealth(®) Inventory (DHI) in clinical practice, we administered the DHI to 360 community dwelling volunteers over age 50 at a Southeastern US rehabilitation hospital. Volunteers also completed surveys to document their health, driving habits, and impressions of the DHI. Volunteers reported strong agreement with statements that indicated that they believe the DHI measures abilities important for safe driving and that they would be willing to listen to advice about driving and safe mobility from medical professionals; however, responses to some items were more positive among drivers whose DHI results indicated no apparent loss of function that could impair driving. These results support the use of the DHI in clinical practice as a tool to raise awareness of factors that correlate to driving; however, further research will be necessary to investigate how the DHI may benefit diverse clinical populations. Experiences with using DHI as part of clinical practice are also discussed.

Development of aphasia, apraxia, and agnosia and decline in Alzheimer's disease.

OBJECTIVE: The purpose of this study was to compare the stage and the subtype models of disease progression in Alzheimer's disease. The authors address the issue of whether the overall rate of clinical decline is different in Alzheimer's disease patients with and without early development of aphasia, apraxia, or agnosia. METHOD: The study was a case series study. Two separate cohorts of Alzheimer's disease patients were used, one from an ongoing single center study at Stanford University (N = 57) and the other from a multicenter project across the state of California (N = 70). Patients were assessed every 6 months in the Stanford study and yearly in the state study. All patients were assessed at least three times. The outcome measure was the average rate of decline on the Mini-Mental State examination. RESULTS: The average rates of decline on the Mini-Mental State were computed for each subject. Subjects were then divided among groups according to whether and when they exhibited aphasia, agnosia, or apraxia. The effects of the presence of aphasia, agnosia, or apraxia were assessed by comparing the average rates of decline on the Mini-Mental State. CONCLUSIONS: Alzheimer's disease patients who developed aphasia or apraxia declined more rapidly than those patients who did not develop either sign. These results were not attributable to differences in Mini-Mental State scores at entry into the study. The results suggest the presence of subtypes of Alzheimer's disease in which accelerated decline is associated with the early appearance of certain neurological signs.

Use of the wrist actigraph to study insomnia in older adults.

Measures derived from the wrist actigraph have been found to correlate highly with EEG measures of normal sleep. Although the actigraph has been used to study normal sleep, few studies have used the actigraph as a measure of sleep of elderly insomniacs. The present study, which used elderly insomniacs, sought to investigate the sensitivity of the actigraph to detect the effects of an insomnia treatment. The actigraph was sufficiently sensitive to detect the effect of the sleep restriction therapy used on several sleep measures. Subsidiary analyses suggested that the sleep log, although not an accurate measure of sleep, may be useful as a measure of elderly insomniacs' subjective perception of sleep. Because the actigraph can be used more easily and less expensively than the polysomnogram, the actigraph appears to be a promising measure for assessing the efficacy of treatment interventions in elderly insomniacs.

The methodology of studying decline in Alzheimer's disease.

OBJECTIVE: To present a new model for analyzing longitudinal data. The trilinear model is superior to the commonly used linear model that includes the flawed assumption that decline is uniform throughout the course of disease--an assumption that does not correspond to clinical observations. DESIGN: A longitudinal cohort sample was used to compare the linear and trilinear models. Simulated longitudinal data were generated to assess classification errors with the trilinear model. SUBJECTS AND SETTING: The subjects were 80 patients with Alzheimer's disease tested in a hospital out-patient clinic. METHODS: The trilinear model describes Alzheimer's disease as proceeding through three periods: An initial period of stability before detectable decline, a period of decline, and a final period of stability during which there is no further detectable decline. A program for the Apple Macintosh computer is available at no charge to apply the model to data. FINDINGS: The analyses indicated that the trilinear model provides a better reflection of decline in Alzheimer's disease than does the linear model. This advantage is present whether the periods of stability reflect a "true" lack of decline or insensitivity of a measurement instrument. CONCLUSIONS: The trilinear model provides not only a more accurate estimate of the average rate of change, but also (when possible) estimates of the point at which decline begins and ends. Also, more detailed comparisons of tests could be made by using the trilinear parameters. The trilinear model would benefit researchers engaged in longitudinal research of progressive disorders.

The relations among caregiver stress, "sundowning" symptoms, and cognitive decline in Alzheimer's disease.

OBJECTIVE: To investigate the relations among the initial perceived stress of Alzheimer patients' caregivers, the rate of change of perceived stress, patients' sundowning behaviors, and patients' rate of cognitive decline. DESIGN: A longitudinal cohort study in which Alzheimer patients and their caregivers were assessed at 6-month intervals. SETTING: Hospital out-patient clinic. Patients and caregivers lived at home. SUBJECTS: Subjects were 35 patients (50-79 years) with Alzheimer's disease and their primary caregivers (24 males and 11 females); all caregivers were spouses. METHODS: At time of entry into the study, caregivers indicated which of seven behaviors indicative of sundowning were exhibited by the patient. Patients were evaluated successively using the Mini-Mental State Examination, whereas caregivers completed the Perceived Stress Scale, provided an index of social support utilization, and completed the Beck Depression Inventory. MAIN OUTCOME MEASURES: Caregivers' initial perceived stress and the rate of change of perceived stress, patients' sundowning behavior, and rate of cognitive decline. RESULTS: The pattern of correlations indicated that both rate of cognitive decline and initial sundowning behavior were significantly correlated with initial perceived caregiver stress. The average rate of increase of caregivers' perceived stress was positively correlated with the initial incidence of sundowning behaviors, even when controlling for the effects of caregiver depression and social support utilization. CONCLUSION: Sundowning behavior of Alzheimer patients is associated with an increased rate of change of caregivers' perceived stress. This association may be specific to sundowning behavior because there was no relation between the rate of change of perceived stress and morning agitation. The findings suggest that future caregiver intervention programs could profitably focus on sundowning behavior rather than general agitation.

Selected psychiatric symptoms associated with rate of cognitive decline in patients with Alzheimer's disease.

We examined the relation between selected psychiatric symptoms and the average rate of decline in different areas of cognition in patients with Alzheimer's disease. Measures of decline were computed by determining patients' average rates of decline on the underlying factors of the Mini-Mental State Examination (MMSE). Patients with agitation or wandering declined more rapidly on the total MMSE score than did patients without either symptom. The Following Commands factor accounted for almost all of this decline. The findings suggest a relation between the presence of certain behavioral problems in Alzheimer's disease and decline in particular cognitive areas.

An actigraphic comparison of sleep restriction and sleep hygiene treatments for insomnia in older adults.

We compared the efficacy of sleep restriction therapy combined with sleep hygiene, nap modification of sleep restriction therapy combined with sleep hygiene, and sleep hygiene alone as treatments for insomnia in 39 community-dwelling men and women 55 years and older. We used the wrist actigraph as an objective outcome measure for all subjects at baseline, end of treatment, and 3-month follow-up; polysomnography (PSG) was conducted in a subgroup of subjects. Although subjects appeared to follow restriction instructions through follow-up, we found few between-group differences in treatment efficacy. Lack of treatment effect might be explained by the efficacy of HYG as a treatment in itself and the relatively low symptom level in these healthy older poor sleepers. At baseline, actigraphic results were found to correlate more highly than sleep log data with PSG in our sample. Actigraphic total sleep time, in particular, was highly correlated with PSG.

Typography manipulations can affect priming of word stem completion in older and younger adults.

The experiments reported here investigated whether changes of typography affected priming of word stem completion performance in older and younger adults. Across all experiments, the typeface in which a word appeared at presentation either did or did not match that of its 3-letter stem at test. In Experiment 1, no significant evidence of a typography effect was found when words were presented with a sentence judgment or letter judgment task. However, subsequent experiments revealed that, in both older and younger adults, only words presented with a syllable judgment task gave rise to the typography effect (Experiments 2-4). Specifically, performance was greater, when the presentation and test typeface matched than when they did not. Experiment 5, which used stem-cued recall, did not reveal a difference between syllable and letter judgment tasks. These findings highlight the complex nature of word stem completion performance.

Perceptions of life stress and chronic insomnia in older adults.

This study compared the level of self-reported stress of 42 older good sleepers (M age = 68.2 years) and 42 poor sleepers (M age = 68.7 years). The relations among subjective ratings of sleep, level of perceived stress, and negative mood were analyzed for each group. Good and poor sleepers reported similar amounts of life stress, but the relations between life stress and sleep perceptions differed for the 2 groups. Specifically, within the group of poor sleepers, those with higher life stress had greater difficulty falling asleep and less early morning waking than did poor sleepers with lower life stress. There was no association between life stress and any sleep measures for good sleepers. These results are compatible with the notion that good and poor sleepers may have different susceptibilities to poor sleep despite experiencing similar stressful life events.

Recognition memory and the mere exposure effect.

Repeated exposure to novel stimuli tends to make the stimuli better liked. Examined here is the relation between this increment in liking and recognition of the stimuli. An attempt was made to replicate findings taken as evidence that liking is used as a basis for inferring prior exposure and thus for making recognition decisions (e.g., Matlin, 1971; Moreland & Zajonc, 1977). The claim was not supported. Although in each of five experiments liking and recognition were positively correlated, liking was less sensitive to prior exposure than was recognition. Moreover, statistical analyses suggested that if liking and recognition were causally related, recognition mediated liking rather than the other way around.

Further evidence of the intricacy of memory span.

Memory span was measured for lists of verbal items constructed such that the items in the first half of the list were of one category and those of the second half were of another. In Experiment 1, the lists consisted of digits and words (e.g., 2, 8, 7, horse, cow, sheep or horse, cow, sheep, 2, 8, 7); in Experiment 2, they consisted of words from the same semantic domain and words from different semantic domains; in Experiments 3 and 4, they consisted of words that rhymed and words that did not rhyme. A category-order effect occurred in each experiment: Span was larger when the digits, same-domain words, or rhyming words occurred in the first half of the list than when they occurred in the second half. These findings suggest that memory span is more complex than is generally assumed.

A comment on age at onset as a subtype of Alzheimer disease.

Subtypes of Alzheimer disease (AD) can be approached from different ways. An intuitive and commonly proposed subtype relates to the age at onset of disease. Research on age at onset as a subtype has yielded conflicting results that may, in part, reflect different measurement approaches. Refinement of the measurement of change in AD should yield a clearer picture of subtypes, as would closer ties between neuropathologic and clinical work. Thus, it is suggested that future research should use measurement techniques that more closely characterize AD than do current approaches. In addition, progress would likely be through attempts to link clinical findings regarding rates of change to neuropathologic findings.

Identification of fast and slow decliners in Alzheimer disease: a different approach.

As the body of knowledge about Alzheimer disease (AD) expands, more evidence is appearing to suggest the existence of different subtypes. The delineation of subtypes is important for a variety of reasons, and there are probably several ways to identify subtypes. One crude but functionally promising distinction is between patients with early onset of AD and those with late onset. In theory, such a distinction appears to be a simple one, but critical methodologic issues are involved in this dichotomy, because a key aspect is estimating the rate of progression of the disease in different subtypes. This article discusses potential problems with various measures of deterioration and illustrates how the application of a novel technique--the trilinear model--can address many of these problems and provide additional valuable information. The trilinear model is especially well suited for use in pharmacologic studies because of the additional insight that it can provide.

Neurology in the art museum: Andrew Wyeth's Christina's World.

Andrew Wyeth's painting of his friend and neighbor Christina Olson, Christina's World, arguably the best known picture by a living American painter, depicts a woman crawling across a field while gazing toward her house. Christina Olson had a lifelong slowly progressive paralytic disorder. Reflections on her life, clinical symptoms, medical evaluation, and her influence on Mr. Wyeth are presented herein.

A study of the problems older adults encounter when using a mnemonic technique.

This study explored problems older adults experience when using a mnemonic technique known as the method of loci. Older subjects received six hours of imagery, judgment, and relaxation pretraining followed by mnemonic training for either four or six hours (Regular or Extended training, respectively). At the end of training, subjects were given a list of the constituent steps of the method of loci and asked to indicate which, if any, were problematic. The factor structure of the relations among the problems varied according to the length of the training subjects received. Specifically, the factor structure of the difficulties reported by the Regular training group reflected problems with using the steps involved in the application of the method of loci, whereas for the Extended training group the factor structure reflected problems with abilities called upon in using the technique. Thus, even with Extended training, subjects may need additional pretraining to develop specific abilities necessary for the successful application of the mnemonic.