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.

Hearing impairment and serial word recall in older adults.

The objective of this work was to study the differences in performance on a nonauditory memory task between older volunteers with and without hearing impairment. The design was cross-sectional. Three-hundred-forty-four community-dwelling adults aged 55 to 93 years, who volunteered for a mnemonic training class served as participants. Participants' hearing was tested with a Maico MA-27 portable audiometer. The dependent measure was performance on a visually presented serial word recall test. Participants were also asked to report whether they had a problem with their hearing. Hearing impairment was associated with poor performance on a serial word recall task, even after controlling for age-related differences on that task. Hearing acuity appears to be related to serial word recall in older adults. Because auditory presentations were not involved, this relation raises the question of whether hearing loss may be concomitant with other changes that affect cognitive abilities.

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.

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.

Predicting response of older adults to mnemonic training: who will benefit?

OBJECTIVES: To identify profiles of subjects who respond to mnemonic training for serial word and proper name recall. DESIGN: Analysis of J. O. Brooks et al.'s (1999) mnemonic training data using Quality Receiver Operating Characteristic (QROC) and longitudinal regression analyses (LRA). SETTING: Community. PARTICIPANTS: 224 community-dwelling adults 55 years of age and older who wished to improve their memory. MEASUREMENTS: Performance on serial word and proper name tests; performance on cognitive ability tests. RESULTS: Although the QROC and LRA identified several common predictors (baseline performance, mental rotation ability, and paired associate learning), the QROC identified additional predictors and cognitive ability profiles associated with successful response. CONCLUSIONS: Similar degrees of response to mnemonic training are associated with heterogeneous cognitive profiles. This finding highlights the fact that participants rely on a variety of abilities to derive benefit from mnemonic training and thus suggests different avenues from which to approach this training.

How to drastically reduce priming in word stem completion--and still present the words.

This paper describes a series of experiments in which we demonstrated that "dysphonemic" word stems, which are likely not pronounced in isolation as they are within a word (e.g., MUS in MUSHROOM or LEG in LEGEND), showed less priming than did "phonemic stems" (e.g., MUS in MUSTARD or LEG in LEGACY). Furthermore, words with either dysphonemic or phonemic three-letter stems gave rise to equivalent levels of priming when test cues were four-letter stems (LEGE) or word fragments (L_G_ND). Moreover, the difference between phonemic and dysphonemic stems persisted when nonpresented completion rates were matched. A final cued-recall experiment revealed that performance was greater for phonemic stems than for dysphonemic stems and that this difference was greater for older participants than for younger ones. These results are not readily accounted for by extant theoretical approaches and point to important methodological issues regarding stem completion.

Taking account of between-patient variability when modeling decline in Alzheimer's disease.

The pattern of deterioration in patients with Alzheimer's disease is highly variable within a given population. With recent speculation that the apolipoprotein E allele may influence rate of decline and claims that certain drugs may slow the course of the disease, there is a compelling need for sound statistical methodology to address these questions. Current statistical methods for describing decline do not adequately take into account between-patient variability and possible floor and/or ceiling effects in the scale measuring decline, and they fail to allow for uncertainty in disease onset. In this paper, the authors analyze longitudinal Mini-Mental State Examination scores from two groups of Alzheimer's disease subjects from Palo Alto, California, and Minneapolis, Minnesota, in 1981-1993 and 1986-1988, respectively. A Bayesian hierarchical model is introduced as an elegant means of simultaneously overcoming all of the difficulties referred to above.

Mnemonic training in older adults: effects of age, length of training, and type of cognitive pretraining.

OBJECTIVES: To improve performance with mnemonic techniques for remembering words and proper names. DESIGN: For word recall, a 2 x 2 factorial in which type of pretraining and length of training were between-subjects manipulations. For proper name recall, a two-group design in which type of pretraining was manipulated between subjects. SETTING: Community. PARTICIPANTS: 268 community-dwelling adults over the age of 55 years who wished to improve their memory. MEASUREMENTS: Recall of words and proper names both before and after training in mnemonics. INTERVENTION: Participants received a 2-week training course on two mnemonic techniques, the method of loci for words and a name association technique for proper names. RESULTS: There was no effect of the pretraining manipulation on proper name recall. For word recall, however, a multiple regression that included age indicated that the older-old participants benefited more from a combination of comprehensive pretraining and extended mnemonic training than did the younger-old. CONCLUSIONS: Increased training time coupled with a comprehensive pretraining regimen can improve the performance of the older-old in using mnemonics; this improved performance cannot be attributed solely to enhanced knowledge of the mnemonic.

Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach.

OBJECTIVES: To assess the longitudinal effects of acety-L-carnitine (ALC) on patients diagnosed with Alzheimer's disease. DESIGN: Longitudinal, double-blind, parallel-group, placebo-controlled. SETTING: Twenty-four outpatient sites across the United States. PARTICIPANTS: A total of 334 subjects diagnosed with probable Alzheimer's disease by NINCDS-ADRDA criteria. These data were originally reported by Thal and colleagues (1996). MEASUREMENTS: Cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) given every 3 months for 1 year. RESULTS: The average rate of change was estimated using the trilinear approach, which allows for periods of both change and stability. Both the ALC group and the placebo group exhibited the same mean rate of change on the ADAS (0.68 points/month). However, a multiple regression analysis revealed a statistically significant Age x Drug interaction characterized by younger subjects benefiting more from ALC, significant, cutpoint for ALC benefit was 61 years of age. CONCLUSIONS: ALC slows the progression of Alzheimer's disease in younger subjects, and the use of the trilinear approach to estimate the average rate of change may prove valuable in pharmacological trials.

Diagnosing Alzheimer's disease in very elderly patients. Relevance of some functional and psychobehavioral aspects assessed by the Gottfries-Bråne-Steen Rating Scale for Dementia. Study Group on Brain Aging, Italian Society of Gerontology and Geriatrics.

OBJECTIVES: To describe the Gottfries-Bråne-Steen (GBS) Rating Scale more fully with instruments commonly used for the diagnostic assessment of older patients with cognitive disturbances--the Mini Mental State Examination (MMSE), Hamilton Depression Rating Scale (HDRS), and Global Deterioration Scale (GDS)--and to characterize the specific diagnostic value of the GBS. DESIGN: A multicenter study including patients diagnosed with senile dementia of the Alzheimer type (SDAT; age at onset: > 75 years) and age-matched non-demented subjects. SUBJECTS: One hundred thirty-eight consecutively referred SDAT patients and 116 non-demented age-matched healthy subjects selected from among relatives of the patients. METHODS: The MMSE, GBS and HDRS were used for assessing patients and controls. The GDS was utilized for dementia staging. FINDINGS: Principal component analysis carried out on GBS scores yielded three factors explaining 74% of variance: factor 1, general functioning; factor 2, depression, and factor 3, restlessness. The actual composition of these factors was analyzed after computing factor scores for each subject by means of forward selection regressions, each using the MMSE, GDS and HDRS as predictors of scores on a given factor. The best predictors were MMSE and GDS scores for factor 1; HDRS for factor 2, and MMSE for factor 3. A GBS cutoff of 8 (obtained after a quality receiver operating characteristic analysis) best discriminated between demented and non-demented subjects (positive-predictive value: 0.88; negative-predictive value: 0.90). CONCLUSIONS: The GBS Rating Scale for dementia can be a useful tool in routine clinical assessment of older subjects with cognitive impairment and distinguishes between demented and non-demented subjects; it gives comprehensive information on functional and psychobehavioral characteristics of demented patients, being composed of factors related to the MMSE and HDRS.

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.

Infants and young children with cystic fibrosis have high levels of serum sialyl Lewis(a) antigen.

Previous studies suggest that serum levels of the mucin-associated sialyl Lewis(a) (Le(a)) antigen (NeuAC alpha 2-3 Gal beta 1-3 [Fuc alpha 1-4]GlcNAc beta 1...) correlate with the pulmonary status of cystic fibrosis (CF) patients who have Le(a) or Lewis(b) blood types and can form the antigen. However, there is little information on serum sialyl Le(a) antigen levels in CF patients or normal children younger than 9 y. We measured serum antigen levels using the MAb 19-9 in normal term neonates, CF infants and young children, and infants and children who had bronchopulmonary dysplasia or asthma. The mean serum sialyl Le(a) antigen level of the CF patients was 46.7 U/mL, significantly above (p < 0.01) the mean levels of the three other groups. The mean serum sialyl Le(a) levels of the three non-CF groups were not significantly different from one another or from published normal values. We conclude that serum sialyl Le(a) antigen levels are elevated early in CF, but are normal in asthma and bronchopulmonary dysplasia patients.

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.

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.

The effects of information load and speech rate on younger and older aircraft pilots' ability to execute simulated air-traffic controller instructions.

In this applied study of memory for orally presented information, 15 younger and 15 older pilots heard recorded air-traffic controller (ATC) messages in the context of six simulated flights. The ATC messages varied in length (3 vs 4 items), speech rate (235 vs 365 wpm), and type of command (course commands consisting of headings and altitudes vs radio/transponder commands consisting of radio frequencies and transponder codes). Older pilots made more execution errors on average and the age difference was greater for the radio/transponder commands, which contained more unique digits than the course commands. Although longer message lengths and faster speech rates led to higher error rates, the increases were not more marked in the older group. Backward digit span was correlated with communication performance, but the older group's lower level of accuracy was not explainable in terms of differences in digit span.

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.