Jill B. Rich

Nonsteroidal anti-inflammatory drugs in Alzheimer's disease

Article abstract-We reviewed the records of 210 patients in the Johns Hopkins Alzheimers Disease Research Center to evaluate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical features and progression of the disease. We compared patients taking NSAIDs or aspirin on a daily basis (N = 32) to non-NSAID patients (N = 177) on clinical, cognitive, and psychiatric measures. The NSAID group had a significantly shorter duration of illness at study entry. Even after controlling for this difference, the NSAID group performed better on the Mini-Mental State Examination, Boston Naming Test, and the delayed condition of the Benton Visual Retention Test. Furthermore, analysis of longitudinal changes over 1 year revealed less decline among NSAID patients than among non-NSAID patients on measures of verbal fluency, spatial recognition, and orientation. These findings support other recent studies suggesting that NSAIDs may serve a protective role in Alzheimers disease. NEUROLOGY 1995;45: 51-55

Implicit memory varies across the menstrual cycle: estrogen effects in young women.

Evidence that ovarian steroid hormones such as estrogen and progesterone affect cognition comes from studies of memory in older women receiving estrogen replacement therapy and studies of sexually dimorphic skills in young women across the menstrual cycle. Sixteen women (ages 18-28) completed tests of memory (implicit category exemplar generation, category-cued recall, implicit fragmented object identification) and sexually dimorphic skills (fine motor coordination, verbal fluency, mental rotations) at the early follicular (low estrogen and progesterone) and midluteal (high estrogen and progesterone) phases of the menstrual cycle. Performance on category exemplar generation, a test of conceptual implicit memory, was better at the midluteal than the follicular phase. In contrast, performance on a test of explicit memory, category-cued recall, did not vary across the menstrual cycle. At Session 1, women in the follicular phase performed better on the fragmented object identification task than did those in the midluteal phase. This unexpected finding suggests that high levels of ovarian hormones might inhibit perceptual object priming. Results confirmed previous reports of decreased mental rotations and improved motor skills and fluency in the midluteal phase. Estradiol levels correlated positively with verbal fluency and negatively with mental rotations and perceptual priming, which suggest that estrogen, and not progesterone, was responsible for the observed changes in cognition. Mood did not vary across the cycle phases. Overall, the findings suggest that estrogen may facilitate the automatic activation of verbal representations in memory.

Verbal fluency patterns in amnestic mild cognitive impairment are characteristic of Alzheimer's type dementia

Amnestic mild cognitive impairment (aMCI) represents a high-risk factor for Alzheimers disease (AD) and is characterized by a selective decline in episodic memory. Although by definition aMCI is not associated with impaired verbal fluency performance, we examined relative differences between fluency tasks because AD is characterized by poorer semantic than phonemic fluency. Phonemic and semantic fluency trials were administered to 46 healthy controls, 33 patients with aMCI, and 33 patients with AD. Results revealed a progressive advantage (controls > aMCI > AD) in semantic, relative to phonemic fluency. Difference scores between tasks distinguished each group from the others with medium to large effect sizes (d) ranging from 0.49 to 1.07. Semantic fluency relies more on semantic associations between category exemplars than does phonemic fluency. This aMCI fluency pattern reflects degradation of semantic networks demonstrating that initial neuropathology may extend beyond known early changes in hippocampal regions.

Longitudinal analysis of phonemic clustering and switching during word- list generation in Huntington's disease

Two characteristics of word-list generation performance are forming clusters (i.e., contiguous words from the same subcategory) and switching among them. Patients with frontal lobe pathology show reduced switching on letter-cued word generation tasks, and clustering has been associated with temporal lobe functioning. Letter-cued word generation was examined in 72 patients with Huntingtons disease (HD) and 41 healthy participants of equivalent age and education. As predicted, the patients showed reduced switching but normal clustering. In addition, switching but not clustering correlated inversely with disease severity, as measured by both movement and mental status scales. Furthermore, 5-year longitudinal analysis revealed a monotonic decrease in switching over time, whereas clustering performance remained stable. Control participants performed uniformly over time on both measures. These results are consistent with a progressive reduction in cognitive flexibility attributed to disruption of frontal-subcortical circuits secondary to neostriatal pathology in HD.

Prospective memory in amnestic mild cognitive impairment

Individuals with amnestic mild cognitive impairment (aMCI) often complain of difficulty remembering to carry out intended actions, consistent with findings of impaired prospective memory (PM) in this population. In this study, individuals with aMCI (N = 27) performed worse than healthy controls (N = 27) on the Memory for Intentions Screening Test (Raskin, 2004), including on time- and event-based subscales, and recognition of the intentions. The aMCI participants made more errors overall, but the proportion of the various error types did not differ between the two groups. Across all error types, both groups made more retrospective than prospective errors, especially on event-based PM tasks. Overall, the findings suggest that PM impairment in aMCI is associated with deficient cue detection involving both automatic (as in event-based tasks) and more strategic detection (as in time-based tasks) processes. These difficulties are likely due to a combination of problematic retrospective episodic memory (e.g., reduced encoding and/or consolidation of cue-intention pairings) and executive functions (e.g., decreased self-initiation, attention switching, and/or inhibition on memory tasks). Formal assessment of PM may help characterize the nature of the memory impairment among individuals with aMCI in clinical neuropsychological evaluations.

Developmental relations between working memory and inhibitory control

Working memory (WM) and inhibitory control (IC) are general-purpose resources that guide cognition and behavior. In this study, the developmental relations between WM and IC were investigated in 96 typically developing children aged 6 to 17 years in an experimental task paradigm using an efficiency metric that combined speed and accuracy performance. The ability to activate and process information in WM showed protracted age-related growth. Performance involving WM and IC together was empirically distinguishable from that involving WM alone. The results indicate that developmental improvements in WM are attributable to increased processing efficiency in activation, suppression, and strategic resource deployment, and that WM and IC are best studied in novel, complex situations that elicit competition among those resources.

Errorless learning and elaborative self-generation in healthy older adults and individuals with amnestic mild cognitive impairment: Mnemonic benefits and mechanisms

Errorless learning is an intervention that benefits memory performance in healthy older adults and a variety of clinical populations. A limitation of the errorless learning technique is that it is passive and does not involve elaborative processing. We report two studies investigating the added benefits of elaborative, self-generated learning to the errorless learning advantage. We also explored the mnemonic mechanisms of the errorless learning advantage. In both studies, older adults and individuals with amnestic mild cognitive impairment (aMCI) completed four encoding conditions representing the crossing of errorless/errorful learning and self-generated/experimenter-provided learning. Self-generation enhanced the errorless learning benefit in cued recall and cued recognition, but not in free recall or item recognition. An errorless learning advantage was observed for priming of target words, and this effect was amplified for participants with aMCI after self-generated learning. Moreover, the aMCI group showed significant priming of prior self-generated errors. These results demonstrate that self-generation enhances the errorless learning advantage when study and test conditions match. The data also support the argument that errorless learning eliminates the misleading implicit influence of prior errors, as well as the need for explicit memory processes to distinguish targets from errors.

Neuropsychological and Personality Characteristics of Predatory, Irritable, and Nonviolent Offenders: Support for a Typology of Criminal Human Aggression

This article represents an initial attempt to adapt the three most relevant components of Moyer’s animal aggression typology to humans. These include predatory (unemotional, goal-directed), irritable (anger-based), and defensive (fear-based) aggression. As different brain networks are likely involved, the authors hypothesized that executive function and personality tests could differentiate violent from nonviolent criminals and discriminate the types originally classified on the basis of criminal history. Discriminant analyses correctly classified 80% of the violent and nonviolent groups and 74% of the predatory and irritable groups. Of theoretical salience, the predatory group resembled the unimpaired nonviolent group only on the cognitive Integrated Visual and Auditory Continuous Performance Test but was indistinguishable from the impaired irritable aggression group on the Iowa Gambling, suggesting inhibitory deficits primarily in the face of reward opportunity. Implications for the theory and application to risk assessment are discussed.

Adjustment to residential placement in Alzheimer disease patients: does premorbid personality matter?

Aim. To evaluate the influence of premorbid personality on adaptation to placement in a long‐term care facility.

Selective dissociations of sedation and amnesia following ingestion of diazepam

Forty-eight healthy volunteers received 0.2 mg/kg oral diazepam or a placebo in a double-blind manner. The effect of the drug on memory was assessed by the free recall of unrelated word lists, and arousal was assessed by subjective ratings of drowsiness, multiple trials of a digit cancellation task, and the rate at which subjects rehearsed aloud items from the word lists. As expected, diazepam, depressed both memory functioning and all three measures of arousal. However, within the diazepam group, rehearsal rate was the only arousal measure that correlated with performance on the recall task. When looking at change scores, or the degree to which performance deteriorated from baseline to the diazepam condition, digit cancellation reduction was the only arousal measure that correlated with recall deterioration. Analyses also revealed that the three arousal measures did not correlate with each other. Results support the view that the arousal/attentional system is composed of partially independent subsystems with varying relationships to memory functioning.