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Objective: With the increasing focus on reducing medical errors and the aging of the physician workforce has come growing concern for cognitive impairment among physicians. This study sought to establish and validate an approach to detecting neuropsychological impairment among physicians. Method: The neuropsychological test performance of 30 physicians referred clinically for neuropsychological evaluations was compared to that of 39 normal community-practicing urologists. We derived 9 key variables from the cognitive and motor tests as dependent variables. Impairment among the clinically-referred doctors was operationalized as scoring ≤5th percentile of the community physicians on at least 3, 4, 5, or 6 of the 9 variables. Using this approach, all clinically-referred physicians were classified as either "impaired" or "ambiguous." Results: A cutoff of ≥5 impaired test scores provided the best balance among competing models. Using this criterion, 14 of the clinically-referred doctors (46%) were impaired and 16 remained ambiguous. The impaired physicians: (1) were older, (2) were more often suspected of having a neurodegenerative disorder, and (3) were more likely to have discontinued practicing medicine. These findings serve as initial validation of our methodology. Conclusions: Using conservative criteria derived from normal community physicians, we could identify a substantial subgroup of clinically-referred physicians who are unambiguously neurocognitively impaired. Replication and refinement of our method with larger samples are recommended, as are the development of specialty-specific criteria for impairment. [ABSTRACT FROM AUTHOR]

Ketone bodies, the products of fat metabolism, are a source of energy for the brain and are available even when glucose supplies are inadequate (such as with severe carbohydrate deprivation) or its metabolism is faulty (as it is in Alzheimer's disease). This phase I/II randomized clinical trial examined the feasibility of using a modified Atkins diet (MAD) to induce ketogenesis in persons with mild cognitive impairment (MCI) or early AD, and the effect of this diet on memory and other clinical outcomes. In the first 2.5 years of active recruitment, only 27 eligible and willing patients enrolled. After extensive assessment and education, they and their study partners were randomly assigned for 12 weeks to either the MAD or the National Institute on Aging (NIA) recommended diet for seniors. As of April 2018, 9 patients in the MAD arm and 5 in the NIA arm have completed the trial. In spite of extensive teaching, coaching, and monitoring, adherence to both diets was only fair. Among those in the MAD arm who generated at least trace amounts of urinary ketones, there was a large (effect size = 0.53) and statistically significant (p = 0.03) increase in Memory Composite Score between the baseline and week-6 assessment. MAD participants also reported increased energy between baseline and week-6 assessment. Despite challenges to implementing this trial, resulting in a small sample, our preliminary data suggest that the generation of even trace ketones might enhance episodic memory and patient-reported vitality in very early AD. [ABSTRACT FROM AUTHOR]

Background: We previously operationally-defined subtle cognitive decline (SCD) in preclinical Alzheimer's disease (AD) using total scores on neuropsychological (NP) tests. NP process scores (i.e., provide information about how a total NP score was achieved) may be a useful tool for identifying early cognitive inefficiencies prior to objective impairment seen in mild cognitive impairment (MCI) and dementia.Objective: We aimed to integrate process scores into the SCD definition to identify stages of SCD and improve early detection of those at risk for decline.Methods: Cognitively "normal" participants from the Alzheimer's Disease Neuroimaging Initiative were classified as "early" SCD (E-SCD; >1 SD below norm-adjusted mean on 2 process scores or on 1 process score plus 1 NP total score), "late" SCD (L-SCD; existing SCD criteria of >1 SD below norm-adjusted mean on 2 NP total scores in different domains), or "no SCD" (NC). Process scores considered in the SCD criteria were word-list intrusion errors, retroactive interference, and learning slope. Cerebrospinal fluid AD biomarkers were used to examine pathologic burden across groups.Results: E-SCD and L-SCD progressed to MCI 2.5-3.4 times faster than the NC group. Survival curves for E-SCD and L-SCD converged at 7-8 years after baseline. The combined (E-SCD+L-SCD) group had improved sensitivity to detect progression to MCI relative to L-SCD only. AD biomarker positivity increased across NC, SCD, and MCI groups.Conclusions: Process scores can be integrated into the SCD criteria to allow for increased sensitivity and earlier identification of cognitively normal older adults at risk for decline prior to frank impairment on NP total scores. [ABSTRACT FROM AUTHOR]

An anti-Markovnikov selective hydroamination of alkynes with N-silylamines to afford N-silylenamines is reported. The reaction is catalyzed by a bis(amidate)bis(amido)Ti(IV) catalyst and is compatible with a variety of terminal and internal alkynes. Stoichiometric mechanistic studies were also performed. This method easily affords interesting N-silylenamine synthons in good to excellent yields and the easily removable silyl protecting group enables the catalytic synthesis of primary amines. [ABSTRACT FROM AUTHOR]

Identifying, recruiting, and enrolling persons in clinical trials of dementia treatments is extremely difficult. One approach to first-wave screening of potential participants is the use of online assessment tools. Initial studies using the Dementia Risk Assessment (DRA)--which includes a previously validated recognition memory test--support the use of this self-administered assessment to identify individuals with "suspected MCI" or "suspected dementia." In this study, we identified between 71 and 622 persons with suspected dementia and between 128 and 1653 persons with suspected mild cognitive impairment (depending on specific criteria) over the course of 22 months. Assessment tools that can inexpensively and easily identify individuals with higher than average risk for cognitive impairment can facilitate recruitment for large-scale clinical trials for dementia treatments. [ABSTRACT FROM AUTHOR]

The design and synthesis of a mixed 2-pyridonate-Ta(NMe2)3Cl complex for the direct C–H alkylation adjacent to nitrogen in unprotected secondary amines are reported. The hydroaminoalkylation of sterically demanding internal alkenes gives the direct, catalytic formation of C(sp3)–C(sp3) bonds. Substrate scope investigations reveal key strategies for further catalyst development efforts in this 100% atom-economic synthesis of α-alkylated amines. [ABSTRACT FROM AUTHOR]

Most approaches to the detection of presymptomatic or prodromal Alzheimer's disease require the costly collection and analysis of biological samples or neuroimaging measurements. The Dementia Risk Assessment (DRA) was developed to facilitate this detection by collecting self-report and proxy-report of dementia risk variables and episodic memory performance on a free Internet website. We now report two validation studies. In Study 1, 130 community-residing older adults seeking memory screening at senior health fairs were tested using the Mini-Cog, and were then observed while taking the DRA. They were compared to a demographically-matched subsample from our anonymous Internet sample. Participants seeking memory screening had more dementia risk factors and obtained lower scores on the DRA's recognition memory test (RMT) than their Internet controls. In addition, those who failed the Mini-Cog obtained much lower scores on the RMT than those who passed the Mini-Cog. In Study 2, 160 older adults seeking evaluation of cognitive difficulties took the DRA prior to diagnostic evaluations at outpatient dementia clinics. Patients who ultimately received the diagnosis of a dementia syndrome scored significantly lower on the RMT than those diagnosed with other conditions or deemed normal. Lower education, family history of dementia, presence of hypercholesterolemia and diabetes, and memory test score distinguished the dementia and no-dementia groups with around 82% accuracy. In addition, score on the RMT correlated highly with scores on other instruments widely used to detect cognitive decline. These findings support the concurrent validity of the DRA for detecting prevalent cognitive impairment. Prospective studies of cognitively normal persons who subsequently develop dementia will be necessary to establish its predictive validity. [ABSTRACT FROM AUTHOR]

Background/Study Context: The method of loci (MoL) is a complex visuospatial mnemonic strategy. Previous research suggests that older adults could potentially benefit from using the MoL, but that it is too attentionally demanding for them to use in practice. The authors evaluated the hypotheses that training can increase the use of MoL, and that MoL use is associated with better memory. Methods: The authors analyzed skip patterns on response forms for the Auditory Verbal Learning Test (AVLT) in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE; N = 1401) trial using 5 years of longitudinal follow-up. Results: At baseline, 2% of participants skipped spaces. Fewer than 2% of control participants skipped spaces at any visit across 5 years, but 25% of memory-trained participants, taught the MoL, did so. Participants who skipped spaces used more serial clustering, a hallmark of the MoL (p <.001). Trained participants who skipped spaces showed greater memory improvement after training than memory-trained participants who did not skip spaces (Cohen's d =.84, p =.007), and did not differ in the subsequent rate of long-term memory decline through up to 5 years of follow-up. Conclusion: Despite being attentionally demanding, this study suggests that after training, the MoL is used by up to 25% of older adults, and that its use is associated with immediate memory improvement that was sustained through the course of follow-up. Findings are consistent with the notion that older adults balance complexity with novelty in strategy selection, and that changes in strategies used following memory training result in observable qualitative and quantitative differences in memory performance. [ABSTRACT FROM AUTHOR]

Compared with in-person assessment methods, telephone screening for dementia and other cognitive syndromes may improve efficiency of large population studies or prevention trials. We used data from the Alzheimer's Disease Anti-Inflammatory Prevention Trial to compare performance of a four-test Telephone Assessment Battery (TAB) that included the Telephone Interview for Cognitive Status (TICS) to that of a traditional in-person Cognitive Assessment Battery. Among 1,548 elderly participants with valid telephone and in-person screening results obtained within 90 days of each other, 225 persons were referred for a full cognitive diagnostic evaluation that was completed within six months of screening. Drawing on results from this panel of 225 individuals, we used the Capture-Recapture method to estimate population numbers of cognitively impaired participants. The latter estimates enabled us to compare the performance characteristics of the two screening batteries at specified cut-offs for detection of dementia and milder forms of impairment. Although our results provide relatively imprecise estimates of the performance characteristics of the two batteries, a comparison of their relative performance suggests that, at selected cut-off points, the TAB produces results broadly comparable to in-person screening and may be slightly more sensitive in detecting mild impairment. TAB performance characteristics also appeared slightly better than those of the TICS alone. Given its benefits in time and cost when screening for cognitive disorders, telephone screening should be considered for large samples. [ABSTRACT FROM AUTHOR]

The Dementia Risk Assessment (DRA) is an online tool consisting of questions about known risk factors for dementia, a novel verbal memory test, and an informant report of cognitive decline. Its primary goal is to educate the public about dementia risk factors and encourage clinical evaluation where appropriate. In Study 1, more than 3,000 anonymous persons over age 50 completed the DRA about themselves; 1,000 people also completed proxy reports about another person. Advanced age, lower education, male sex, complaints of severe memory impairment, and histories of cerebrovascular disease, Parkinson's disease, and brain tumor all contributed significantly to poor memory performance. A high correlation was obtained between proxy-reported decline and actual memory test performance. In Study 2, 52 persons seeking first-time evaluation at dementia clinics completed the DRA prior to their visits. Their responses (and those of their proxy informants) were compared to the results of independent evaluation by geriatric neuropsychiatrists. The 30 patients found to meet criteria for probable Alzheimer's disease, vascular dementia, or frontotemporal dementia differed on the DRA from the 22 patients without dementia (most other neuropsychiatric conditions). Scoring below criterion on the DRA's memory test had moderately high predictive validity for clinically diagnosed dementia. Although additional studies of larger clinical samples are needed, the DRA holds promise for wide-scale screening for dementia risk. [ABSTRACT FROM AUTHOR]

Compared with in-person assessment methods, telephone screening for dementia and other cognitive syndromes may improve efficiency of large population studies or prevention trials. We used data from the Alzheimer's Disease Anti-Inflammatory Prevention Trial to compare performance of a four-test Telephone Assessment Battery (TAB) that included the Telephone Interview for Cognitive Status (TICS) to that of a traditional in-person Cognitive Assessment Battery. Among 1,548 elderly participants with valid telephone and in-person screening results obtained within 90 days of each other, 225 persons were referred for a full cognitive diagnostic evaluation that was completed within six months of screening. Drawing on results from this panel of 225 individuals, we used the Capture-Recapture method to estimate population numbers of cognitively impaired participants. The latter estimates enabled us to compare the performance characteristics of the two screening batteries at specified cut-offs for detection of dementia and milder forms of impairment. Although our results provide relatively imprecise estimates of the performance characteristics of the two batteries, a comparison of their relative performance suggests that, at selected cut-off points, the TAB produces results broadly comparable to in-person screening and may be slightly more sensitive in detecting mild impairment. TAB performance characteristics also appeared slightly better than those of the TICS alone. Given its benefits in time and cost when screening for cognitive disorders, telephone screening should be considered for large samples. [ABSTRACT FROM AUTHOR]

Spatial location memory has rarely been assessed in young children due to a scarcity of developmentally appropriate tests. This study sought to compare nonverbal learning and recall in children born extremely low birth weight (ELBW; <1000 g) and less than 33 gestational weeks (GW) with term-born children at early school age using a recently developed and adapted test. We administered a modification of the Hopkins Board to 210 children at age six; 84 born ELBW (35 born < 26 GW; 49 born 26–33 GW) and 126 term-born. Six measures were obtained: naming, trials-to-criterion, errors-to-criterion, delayed item recall, delayed location recall, and percent retention. After age correction, ELBW children had worse general cognition, item naming, delayed item recall, delayed location recall, and percent retention than term-born children. Delayed item recall and percent retention performances of ELBW children remained worse after correction for general cognition. ELBW groups (< 26 GW and 26–33 GW) groups performed worse than term-born children in naming and delayed item recall with chronological age as covariate. Those born before 26 GW, but not 26–33 GW, performed worse than term-born children in delayed location recall and percent retention. Differences remained significant after controlling for gender, maternal education, and delivery type. All three groups' performance declined from final learning trial to delayed location recall, with a decline greater for less than 26 GW than term-born children. Extreme prematurity (< 26 GW) and ELBW are significant risk factors for spatial location memory deficit. The modified Hopkins Board discriminated high-risk preterm and term-born children at early school age and appears to be a useful test to measure this rarely studied cognitive capacity. [ABSTRACT FROM AUTHOR]

Background: Reports of low-velocity knee dislocations have focused primarily on dislocations occurring during athletic competition. The authors identified a subset of patients with low-velocity knee dislocations that occurred during activities of daily living, such as stepping off a curb, stepping off a stair, or simply falling while walking (ultra-low-velocity dislocations).Hypothesis: Ultra-low-velocity knee dislocations are common in obese individuals and are associated with more complications than high-velocity knee dislocations.Study Design: Case series; Level of evidence, 4.Methods: A review of records identified 17 patients with knee dislocations that occurred during daily activities. All 17 were clinically obese, with an average body mass index (BMI) of 48 (BMI <25 is normal; ≥40 is severe obesity). Ligament injuries occurred in all 17 patients, neurologic injuries in 7, and popliteal artery injuries in 7. Thirteen (76.4%) of the 17 dislocations were anterior, 2 (11.8%) were posterior, and 2 (11.8%) were lateral. All dislocations were reduced closed and stabilized with splints, crossed pins, or external fixation; ligament reconstructions were done in 8 patients and popliteal artery repairs in 7. Above-knee amputations were required in 2 patients with vascular repairs because of tissue ischemia; 1 patient died from cardiac arrest 7 days after injury; and 3 were lost to follow-up. Of the 11 remaining patients, 6 had ligament reconstructions and 5 did not.Results: Four standardized knee scoring systems (International Knee Documentation Committee [IKDC], Hospital for Special Surgery [HSS], Lysholm, Tegner) were used to evaluate outcome at an average follow-up of 28.5 months. Although scores were low in all patients, those with ligamentous reconstruction had better outcomes (“fair”: 74 ± 22) than those without reconstruction (“poor”: 21 ± 8.5), with a statistically significant (P = .013) difference in HSS scores. Lysholm scores also were higher in those with reconstruction (average 67) than in those without (average 53), but the difference was not statistically significant (P = .45).Conclusion: These results indicate that (1) neurovascular injuries are frequent with these ultra-low-velocity dislocations in severely obese patients, (2) the likelihood of combined neurovascular injury tends to increase as BMI increases, and (3) surgical ligament reconstruction with emphasis on posterolateral corner repair appears to improve outcomes. [ABSTRACT FROM PUBLISHER]

This study was sponsored by the Joint Fire Science Program to understand and enhance the ability of federal land managers to address financial and economic (F&E) aspects of woody biomass removal as a component of fire hazard reduction. Focus groups were conducted with nearly 100 federal land managers throughout the western United States. Several issues and information disconnects were identified in two major areas: the F&E analysis process and the tools and information used for F&E analyses. The most prevalent disconnects appeared to be between managers' knowledge versus acceptance and use of F&E tools developed by research entities. Most managers also tended to focus on financial rather than economic analysis. Findings suggest needs for continually updated local timber and biomass market information; training with F&E tools and methods currently used; ongoing technical support for tools currently used; and closer communication among forest management, research, and administrative personnel as new F&E tools or administrative processes are developed and implemented. [ABSTRACT FROM AUTHOR]

Naming is a fundamental aspect of language and is virtually always assessed with visual confrontation tests. Tests of the ability to name objects by their characteristic sounds would be particularly useful in the assessment of visually impaired patients, and may be particularly sensitive in Alzheimer's disease (AD). We developed an auditory naming task, requiring the identification of the source of environmental sounds (i.e., animal calls, musical instruments, vehicles) and multiple-choice recognition of those not identified. In two separate studies mild-to-moderate AD patients performed more poorly than cognitively normal elderly on the auditory naming task. This task was also more difficult than two versions of a comparable visual naming task, and correlated more highly with Mini-Mental State Exam score. Internal consistency reliability was acceptable, although ROC analysis revealed auditory naming to be slightly less successful than visual confrontation naming in discriminating AD patients from normal participants. Nonetheless, our auditory naming task may prove useful in research and clinical practice, especially with visually impaired patients. [ABSTRACT FROM AUTHOR]

Abstract: Some individuals with psychogenic nonepileptic seizures (PNES) are seen as having adopted a “sick role” that relinquishes them of responsibility for meeting stressful life demands. Thus, patients with PNES may have positive, albeit unrecognized, attitudes toward seizures, or perhaps illness in general. Because such covert attitudes may not be amendable to self-report, the current study used the Implicit Association Test (IAT), a methodology by which attitudes toward illness and disability can be inferred from performance on an ostensibly neutral task. Individuals with PNES did not have a reduced interference effect when responding to sickness-related and pleasant words on the same response key. Exploratory analyses revealed that a pronounced somatic focus and higher extraversion were associated with more neutral attitudes toward illness among patients with PNES. This IAT methodology found little support for the notion that patients with PNES harbor positive attitudes toward illness. Limitations of the IAT methodology are reviewed and recommendations are provided. [ABSTRACT FROM AUTHOR]

Differences in the memory characteristics of patients with Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD) were investigated with tests that assess learning and retention of words, line-drawn objects, and locations. Large groups of AD, HD, and PD patients were administered the Hopkins Verbal Learning Test-Revised (HVLT-R) and the Hopkins Board (HB). Eight learning and memory measures were subjected to discriminant function analysis. A 91% classification accuracy was achieved for the separation of cortical and subcortical dementias and 79% accuracy for the discrimination of the three groups. The delayed recall of items was the best discriminator. Receiver-operating curve analysis indicated up to 90% sensitivity and 90% specificity in differentiating the three diseases using the discriminant scores. Individual learning and memory measures of the HVLT-R and the HB provided very high sensitivity and specificity in distinguishing cortical versus subcortical dementias and modest accuracy in separating the two subcortical diseases. [ABSTRACT FROM PUBLISHER]

Objective Elderly persons with mild cognitive impairment (MCI) are at increased risk of dementia and functional impairments. The present study investigated the contribution of three domains of executive cognition to everyday functioning among persons with MCI. Methods 124 MCI patients and 68 cognitively normal elderly participants were administered a cognitive screening battery. These tests were used to divide patients into four subgroups (amnestic single domain, amnestic multiple domain, non-amnestic single domain, and non-amnestic multiple domain). Subjects were then administered 18 executive function tests that assess planning/problem-solving, working memory, and judgment. Performance of everyday activities and everyday cognition was rated with two informant-reported measures. Results All MCI subtypes had more difficulties in everyday activities than cognitively normal elderly participants. Multiple domain MCI patients had more functional impairments than single domain MCI patients. Contrary to our expectations, only one executive function component, working memory, contributed significantly to functional status after controlling for demographic, health-related and other cognitive factors. Conclusions Functional abilities are compromised in all MCI subtypes. Working memory may be associated with functional impairments, but general cognitive measures account for more unique variance. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Patients with amnestic mild cognitive impairment (aMCI) have been described as exhibiting greater impairment on tests of category fluency than letter fluency. This has been offered as evidence that this condition represents pre-clinical Alzheimer's disease (AD). We hypothesized that this pattern of differential impairment is dependent on the specific semantic categories and initial letters selected, and is not specific to AD and aMCI. A total of 40 cognitively normal older adults, 74 MCI patients—25 “amnestic single domain” (aMCI), 27 “amnestic multiple domain”, and 22 non-amnestic—and 29 AD patients were tested with multiple forms of semantic-category and initial-letter fluency tasks. The pattern of deficits within and across groups was highly dependent on the specific categories and letters chosen. Overall, aMCI patients did not demonstrate greater impairment in category than letter fluency. In fact, the level and pattern of their performance resembled that of cognitively normal older adults much more than AD patients. MCI patients with deficits in multiple cognitive domains performed most like AD patients. These findings indicate that verbal fluency performance is highly influenced by the specific tasks used, and impairment on semantic fluency is not characteristic of pure amnestic MCI. [ABSTRACT FROM AUTHOR]

This address to the International Neuropsychological Society membership challenges the wisdom of several common practices in contemporary neuropsychology. It is argued that, in spite of their popularity, the development of race-specific test norms, the indiscriminate use of Bonferroni's correction for multiple comparisons, and the conduct of "quality of life" research are all conceptually problematic. These practices may have untoward sociopolitical effects as well, and neuropsychologists are urged to exercise caution before embracing them. [ABSTRACT FROM AUTHOR]

Purpose: Long-term neuropsychological outcome was studied in 71 patients who underwent hemispherectomy for severe and intractable seizures at The Johns Hopkins Hospital between 1968 and 1997 and who agreed to participate. Seizures were due to cortical dysplasias (n = 27), Rasmussen syndrome (n = 37), or vascular malformations or strokes (n = 7). Both presurgical and follow-up results are available and reported for 53 patients. Methods: Patients and caretakers were interviewed, and patients were administered standard measures of intelligence, receptive and expressive language, visual-motor skills, adaptive/developmental functioning, and behavior. Results: Mean age at surgery was 7.2 years. At follow-up, on average 5.4 years after surgery, 65% are seizure free, 49% are medication free, and, of those responding, none rated quality of life as worse than before surgery. Mean IQ was in the 70s for Rasmussen and vascular patients and in the 30s for cortical dysplasia patients. Language and visual-motor skills were consistent with IQ. For Rasmussen patients only, language was significantly more impaired for left than for right hemispherectomy, both before surgery and at follow-up. Adaptive skills were mildly impaired, with greatest impairment in the physical domain. Cognitive measures typically changed little between surgery and follow-up, with IQ change <15 points for 34 of 53 patients; of the remainder, 11 declined and eight improved. Behavior was free of major problems, but social interactions and activities were limited. Conclusions: The most significant predictor of cognitive skills at follow-up was etiology, with dysplasia patients scoring lowest in intelligence and language but not in visual-motor skills. Regardless of etiology, most patients showed only moderate change in cognitive performance at follow-up. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and safety of donepezil, an acetylcholinesterase inhibitor, as a treatment for cognitive impairment and dementia in patients with Parkinson' s disease (PD). Methods Using a randomized, double-blind, placebo-controlled design, nine patients received placebo and seven patients received donepezil (2.5–10 mg/day) for a mean (SD) duration of 15.2 (3.4) weeks. The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory, attention, psychomotor speed, and visuospatial and executive functions. Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings. Primary safety measures were motor signs and assessments of adverse effects. Results Patients on donepezil showed selective and significant (p <0.05) improvement on the memory subscale of the Dementia Rating Scale. There was also a trend toward improvement on a measure of psychomotor speed and attention. There were no group differences in psychiatric status, motor function, or activities of daily living as measured at baseline or end-point. Adverse effects resulted in premature withdrawal of four patients on donepezil, two for peripheral cholinergic effects and one for increased parkinsonism. Side effects were associated with dosage increases. Conclusion Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment. However, variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD, especially with dosage increases. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

While it is clear that central nervous system (CNS) lesions in systemiclupus erythematosus (SLE) adversely affect cognitive functioning, it is alsoevident that patients without visible lesions (non-CNS SLE) may also exhibitsubtle cognitive impairment. The presence of antiphospholipid antibodies (aPLs)has been proposed as a marker of disease severity and hence should be correlatedwith neuropsychological dysfunction in this population. The current studycompared groups of non-CNS lupus patients who were positive (LA+) or negative(LA-) for aPLs on selected measures of neuropsychological functioning.In addition, we attempted to characterize the pattern of cognitive impairmentthat is associated with LA status in these patients. No coherent neuropsychologicalpattern emerged, but LA+ patients performed worse than LA- patientson measures assessing attention, concentration, and visual search, as wellas spatial learning and memory. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to develop an algorithm that predicts survival in patients with dementia upon entry into long-term care. There are, as yet, no predictive equations developed for those in the late stages of Alzheimer's disease (AD).Methods: This was a prospective, observational study of 132 patients with dementia (61% with AD) followed for up to 5.0 years (median of 41.0 months) after admission to a long-term care facility for dementia patients. Information on demographic characteristics, physical health, and cognitive, emotional, and behavioral characteristics was collected shortly after admission and entered as predictors of time until death in Cox regressions. Findings were used to derive an index predicting mortality.Results: There were 60 deaths among the 132 patients (45.4% mortality), with an average survival of 22.4 months in those who died. Better physical health and the presence of delusions were associated with longer survival. These two variables were aggregated into the Copper Ridge Index (CRI). Each one-point increase on the CRI was associated with a four-fold greater likelihood of death over 5 years.Conclusions: A predictive equation incorporating measures of general physical health and delusions accurately predicted time to death in dementia patients in long-term care. [ABSTRACT FROM AUTHOR]

Reports that movement jerkiness, which characterizes the smoothness and efficiency of motion was a sensitive indicator of presymptomatic Huntington's disease (HD). Observation that a large fraction of asymptomatic HD gene-carriers displayed elevated jerk even when more than seven years remained until predicted disease onset; Suggestion that a dysfunction in error correction characterizes the motor control deficit in early HD.

The article discusses episodes of psychogenic nonepileptic seizures (PNES) and its treatment as a disorder of behavior. Topics discussed include epidemiology and risk factors, associated psychological disorders as major depression and anxiety disorder, and its evaluation and diagnosis through video-electroencephalography (video-EEG) and psychological testing. The fundamentals of treatment are also discussed including the withdrawal of antiepileptic medications and neurodiagnostic testing.

Aim . To evaluate the influence of premorbid personality on adaptation to placement in a long-term care facility. Subjects . Twenty-eight persons with probable Alzheimer disease (AD) residing in an academically affiliated nursing home for 6–9 months. Methods . Premorbid personality was described retrospectively by two informants for each resident using the revised NEO Personality Inventory (NEO-PI-R). Standardized tests and rating scales were used on admission to the facility to assess cognition, mood state, physical dependency and general health. Nurses rated each AD resident's social behaviour, participation in activities and quality of sleep. Results . Poorer adjustment was associated with more severe dementia but better physical health. None of the NEO-PI-R domain scores predicted adjustment. Conclusions . Contrary to popular belief, premorbid personality is relatively inconsequential for an AD patient's adaptation to a long-term care facility. © 1998 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Reports on the Johns Hopkins University School of Medicine's initiation of a voluntary program of presymptomatic genetic testing for Huntington's disease for persons at 50 percent risk. Absence of severe depressive reactions; Suggestion that people who receive genetic test results cope well, al least over the short term, when the testing is performed in a clinical context.

The use of amnesia as a legal defense raises complex issues for both psychology and jurisprudence. Our review of the legal literature suggests that recent advantages in the understanding of clinical disorders of memory have not yet found their way into the courtroom. In this paper, we address the assumptions that amnesia means simply having a very bad memory and that amnesia is a unitary syndrome. We then review recent neuropsychological research on amnesia and its implications for the judicial process. Emphasis is placed on describing the amnesia disorders that most often arise in criminal proceedings. It is concluded that both psychologists and legal professionals should ensure that research findings from the clinic and the laboratory are applied appropriately in cases of defendants claiming amnesia. [ABSTRACT FROM AUTHOR]

Fuentes-Albero and colleagues [[5]] report that Spanish schoolchildren with attention-deficit hyperactivity disorder (ADHD) consume diets that are lower in I i -3 PUFAs than their peers without ADHD. They found that all laboratory studies of rodents found significant deleterious effects of high-fat diets compared to standard diets. 1 G mez-Pinilla F. Brain foods: The effects of nutrients on brain function. [Extracted from the article]

Sex is an important factor to consider when evaluating memory with older adults. This present study aimed to examine sex differences in memory within a clinical sample of older adults (N = 1084). Raw learning and recall scores on the Hopkins Verbal Learning Test, Revised (HVLT-R) and Brief Visuospatial Memory Test, Revised (BVMT-R) were compared between sexes within the entire sample and cohorts stratified by age. Within the entire sample, women outperformed men in HVLT-R learning and recall, and there were no sex differences in BVMT-R performance. These sex differences, however, were absent or reversed for those with impaired HVLT-R performance and functional deficits, indicating that women retain an early advantage in verbal memory, which is lost with greater indication of disease severity. These findings indicate that women retain an advantage in verbal learning and memory, at least before significant levels of impairment, within a sample of older adults seen at an outpatient neurology clinic, which may have implications for diagnosing memory disorders. [ABSTRACT FROM AUTHOR]

Prior research has demonstrated the importance of a healthy lifestyle to protect brain health and diminish dementia risk in later life. While a multidomain lifestyle provides an ecological perspective to voluntary engagement, its association with brain health is still under-investigated. Therefore, understanding the neural mechanisms underlying multidomain lifestyle engagement, particularly in older adults at risk for Alzheimer's disease (AD), gives valuable insights into providing lifestyle advice and intervention for those in need. The current study included 139 healthy older adults with familial risk for AD from the Prevent-AD longitudinal aging cohort. Self-reported exercise engagement, cognitive activity engagement, healthy diet adherence, and social activity engagement were included to examine potential phenotypes of an individual's lifestyle adherence. Two adherence profiles were discovered using data-driven clustering methodology [i.e., Adherence to healthy lifestyle (AL) group and Non-adherence to healthy lifestyle group]. Resting-state functional connectivity matrices and grey matter brain features obtained from magnetic resonance imaging were used to classify the two groups using a support vector machine (SVM). The SVM classifier was 75% accurate in separating groups. The features that show consistently high importance to the classification model were functional connectivity mainly between nodes located in different prior-defined functional networks. Most nodes were located in the default mode network, dorsal attention network, and visual network. Our results provide preliminary evidence of neurobiological characteristics underlying multidomain healthy lifestyle choices. [ABSTRACT FROM AUTHOR]

The tantalum complex TAP is found to be the optimal catalyst for the title reaction of unprotected secondary amine substrates with sterically demanding internal (E) and (Z) alkenes. [ABSTRACT FROM AUTHOR]

A definitive diagnosis of Alzheimer's disease (AD), even in the presence of co-morbid neuropathology (occurring in > 50% of AD cases), is a significant unmet medical need that has obstructed the discovery of effective AD therapeutics. An AD-biomarker, the Morphometric Imaging (MI) assay on cultured skin fibroblasts, was used in a double-blind, allcomers (ages 55–90) trial of 3 patient cohorts: AD dementia patients, N = 25, all autopsy confirmed, non-AD dementia patients, N = 21—all autopsy or genetically confirmed; and non-demented control (AHC) patients N = 27. Fibroblasts cells isolated from 3-mm skin punch biopsies were cultured on a 3-D Matrigel matrix with movement dynamics quantified by image analysis. From counts of all aggregates (N) in a pre-defined field image and measures of the average area (A) of aggregates per image, the number-to-area ratios in a natural logarithmic form Ln(A/N) were determined for all patient samples. AD cell lines formed fewer large aggregates (cells clustered together) than non-AD or AHC cell lines. The cut-off value of Ln(A/N) = 6.98 was determined from the biomarker values of non-demented apparently healthy control (AHC) cases. Unequivocal validation by autopsy, genetics, and/or dementia criteria was possible for all 73 patient samples. The samples were collected from multiple centers—four US centers and one center in Japan. The study found no effect of center-to-center variation in fibroblast isolation, cell growth, or cell aggregation values (Ln(A/N)). The autopsy-confirmed MI Biomarker distinguished AD from non-AD dementia (non-ADD) patients and correctly diagnosed AD even in the presence of other co-morbid pathologies at autopsy (True Positive = 25, False Negative = 0, False Positive = 0, True Negative = 21, and Accuracy = 100%. Sensitivity and specificity were calculated as 100% (95% CI = 84 to 100.00%). From these findings, the MI assay appears to detect AD with great accuracy—even with abundant co-morbidity. [ABSTRACT FROM AUTHOR]

Presents a statement from the American Academy of Clinical Neuropsychology on the use of non-doctoral-level personnel in conducting neuropsychological evaluations. Acceptability of the practice in the field of clinical neuropsychology; Scope of responsibility.

Presents an obituary for neuropsychologist Nelson M. Butters who died on November 18, 1995.

Replies to comments made by Q.W.J. Quarrell et al to an article in the 'Journal of the American Medical Association,' in which they highlighted some of the social issues raised by presymptomatic diagnosis of disease with molecular genetic tests.

Objective: Although small strokes typically result in "good" functional outcomes, significant cognitive impairment can occur. This longitudinal study examined a cohort of patients with minor stroke to determine the pattern of deficits, evolution over time, and factors associated with outcome. Methods: Patients admitted to the hospital with their first clinical minor stroke (NIH Stroke Scale [NIHSS] ≤ 10, absence of severe hemiparesis, aphasia, or neglect) were assessed at 1 month post‐infarct, and a subset were followed over time (with 6‐ and 12‐month evaluations). Composite scores at each time point were generated for global cognition, verbal memory, spatial memory, motor speed, processing speed, and executive function. Paired t‐tests evaluated change in scores over time. Regression models identified factors associated with initial performance and better recovery. Results: Eighty patients were enrolled, evaluated at 1 month, and prospectively followed. The average age of the participants was 62.3 years, and mean education was 13.5 years. The average stroke volume was 6.6 cc; mean NIHSS score was 2.8. At 1 month, cognitive scores were below the normative range and > 1 standard deviation below the patient's peak ("recovery") score for every cognitive domain, strongly suggesting that they were well below patients' prestroke baselines. Forty‐eight patients followed up at 6 months, and 39 at 12 months. Nearly all (98%) patients significantly improved in global cognition (averaged across domains) between 1 and 6 months. Between 6 and 12 months, recovery was variable. Higher education, occupational class, and Caucasian race were associated with higher recovery scores for most domains. Conclusions: Cognitive impairment across multiple domains is common following minor stroke regardless of infarct location, suggesting a global process such as network dysfunction that improves over 6 months. Degree of recovery can be predicted using baseline factors. [ABSTRACT FROM AUTHOR]

Background: The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies. Objective: To develop and validate a prediction algorithm that uses data from a single visit to estimate time to important disease endpoints for individual Alzheimer's disease patients. Method: Two separate study cohorts (Predictors 1, N = 252; Predictors 2, N = 254), all initially with mild Alzheimer's disease, were followed for 10 years at three research centers with semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. The prediction algorithm was based on a longitudinal Grade of Membership model developed using the complete series of semiannually-collected Predictors 1 data. The algorithm was validated on the Predictors 2 data using data only from the initial assessment to predict separate survival curves for three outcomes. Results: For each of the three outcome measures, the predicted survival curves fell well within the 95% confidence intervals of the observed survival curves. Patients were also divided into quintiles for each endpoint to assess the calibration of the algorithm for extreme patient profiles. In all cases, the actual and predicted survival curves were statistically equivalent. Predictive accuracy was maintained even when key baseline variables were excluded, demonstrating the high resilience of the algorithm to missing data. Conclusion: The new prediction algorithm accurately predicts time to death, institutionalization, and need for full-time care in individual Alzheimer's disease patients; it can be readily adapted to predict other important disease endpoints. The algorithm will serve an unmet clinical, research, and public health need. [ABSTRACT FROM AUTHOR]

Background: The ability to predict the length of time to death and institutionalization has strong implications for Alzheimer's disease patients and caregivers, health policy, economics, and the design of intervention studies.Objective: To develop and validate a prediction algorithm that uses data from a single visit to estimate time to important disease endpoints for individual Alzheimer's disease patients.Method: Two separate study cohorts (Predictors 1, N = 252; Predictors 2, N = 254), all initially with mild Alzheimer's disease, were followed for 10 years at three research centers with semiannual assessments that included cognition, functional capacity, and medical, psychiatric, and neurologic information. The prediction algorithm was based on a longitudinal Grade of Membership model developed using the complete series of semiannually-collected Predictors 1 data. The algorithm was validated on the Predictors 2 data using data only from the initial assessment to predict separate survival curves for three outcomes.Results: For each of the three outcome measures, the predicted survival curves fell well within the 95% confidence intervals of the observed survival curves. Patients were also divided into quintiles for each endpoint to assess the calibration of the algorithm for extreme patient profiles. In all cases, the actual and predicted survival curves were statistically equivalent. Predictive accuracy was maintained even when key baseline variables were excluded, demonstrating the high resilience of the algorithm to missing data.Conclusion: The new prediction algorithm accurately predicts time to death, institutionalization, and need for full-time care in individual Alzheimer's disease patients; it can be readily adapted to predict other important disease endpoints. The algorithm will serve an unmet clinical, research, and public health need. [ABSTRACT FROM AUTHOR]

Objective. To investigate the influence of memory training on initial recall and learning. Method. The Advanced Cognitive Training for Independent and Vital Elderly study of community-dwelling adults older than age 65 (n = 1,401). We decomposed trial-level recall in the Auditory Verbal Learning Test (AVLT) and Hopkins Verbal Learning Test (HVLT) into initial recall and learning across trials using latent growth models. Results. Trial-level increases in words recalled in the AVLT and HVLT at each follow-up visit followed an approximately logarithmic shape. Over the 5-year study period, memory training was associated with slower decline in Trial 1 AVLT recall (Cohen’s d = 0.35, p = .03) and steep pre- and posttraining acceleration in learning (d = 1.56, p < .001). Findings were replicated using the HVLT (decline in initial recall, d = 0.60, p = .01; pre- and posttraining acceleration in learning, d = 3.10, p < .001). Because of the immediate training boost, the memory-trained group had a higher level of recall than the control group through the end of the 5-year study period despite faster decline in learning. Discussion. This study contributes to the understanding of the mechanisms by which training benefits memory and expands current knowledge by reporting long-term changes in initial recall and learning, as measured from growth models and by characterization of the impact of memory training on these components. Results reveal that memory training delays the worsening of memory span and boosts learning. [ABSTRACT FROM PUBLISHER]

Objective. To examine the measurement equivalence of items on disability across three international surveys of aging. Method. Data for persons aged 65 and older were drawn from the Health and Retirement Survey (HRS, n = 10,905), English Longitudinal Study of Aging (ELSA, n = 5,437), and Survey of Health, Ageing and Retirement in Europe (SHARE, n = 13,408). Differential item functioning (DIF) was assessed using item response theory (IRT) methods for activities of daily living (ADL) and instrumental activities of daily living (IADL) items. Results. HRS and SHARE exhibited measurement equivalence, but 6 of 11 items in ELSA demonstrated meaningful DIF. At the scale level, this item-level DIF affected scores reflecting greater disability. IRT methods also spread out score distributions and shifted scores higher (toward greater disability). Results for mean disability differences by demographic characteristics, using original and DIF-adjusted scores, were the same overall but differed for some subgroup comparisons involving ELSA. Discussion. Testing and adjusting for DIF is one means of minimizing measurement error in cross-national survey comparisons. IRT methods were used to evaluate potential measurement bias in disability comparisons across three international surveys of aging. The analysis also suggested DIF was mitigated for scales including both ADL and IADL and that summary indexes (counts of limitations) likely underestimate mean disability in these international populations. [ABSTRACT FROM PUBLISHER]

Persons who have the genetic mutation responsible for Huntington's disease (HD) have been shown to exhibit lower cognitive test scores years prior to manifest HD. Most studies have examined cognitive performance in presymptomatic persons by using estimated times to manifest HD based on published algorithms. We followed 19 gene-positive persons who were presymptomatic using an objective criterion (i.e., Quantified Neurological Exam score ≤ 10) at baseline for up to 21 years (median = 5 years) with periannual neuropsychological assessments until a diagnosis of manifest HD. Results showed that our tests of information- and psychomotor-processing speed that place minimal demands on cognition, worsening performance became evident 5–10 years prior to the development of manifest HD. In conclusion, cognitive decline precedes motor signs in HD and may be an important target in clinical trials and early intervention. Cognitive test scores may also improve the ability to predict disease onset among gene mutation carriers and help families to better plan for potential personal and economic hardship. [ABSTRACT FROM PUBLISHER]

Cognitive impairment is common in Parkinson's disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen for dementia and mild cognitive impairment in clinical trials of PD where cognition is not the primary outcome. This Task Force conducted a systematic literature search for cognitive assessments previously used in a PD population. Scales were then evaluated for their appropriateness to screen for cognitive deficits in clinical trials, including brief administration time (<15 minutes), assessment of the major cognitive domains, and potential to detect subtle cognitive impairment in PD. Five scales of global cognition met the predetermined screening criteria and were considered for review. Based on the Task Force's evaluation criteria the Montreal Cognitive Assessment (MoCA), appeared to be the most suitable measure. This Task Force recommends consideration of the MoCA as a minimum cognitive screening measure in clinical trials of PD where cognitive performance is not the primary outcome measure. The MoCA still requires further study of its diagnostic utility in PD populations but appears to be the most appropriate measure among the currently available brief cognitive assessments. Widespread adoption of a single instrument such as the MoCA in clinical trials can improve comparability between research studies on PD. © 2010 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background. Although there has been much research devoted to understanding the predictors of nursing home placement (NHP) in Alzheimer's disease (AD) patients, there is currently a lack of research conceming the predictors of home health care. The objective of this study was to examine whether the Dependence Scale can predict home health aide (HHA) use. Methods. The sample is drawn from the Predictors Study, a large, multicenter cohort of patients with probable AD, prospectively followed annually for up to 7 years in three university-based AD centers in the United States. Markov analyses (n = 75) were used to calculate annual transition probabilities for the "new onset" of HHA use (instances where an HHA was absent at the previous Visit, but present at the next visit) as a function of HHA presence at the preceding year's visit and dependence level at that preceding year's visit. Results. The dependence level at the previous year's visit was a significant predictor of HHA use at the next years visit. Three specific items of the Dependence Scale (needing household chores done for oneself, needing to be watched or kept company when awake, and needing to be escorted when outside) were significant predictors of the presence of an HHA. Conclusion. The Dependence Scale is a valuable tool for predicting HHA use in AD patients. Obtaining a better understanding of home health care in AD patients may help delay NHP and have a positive impact on the health and well- being of both the caregiver and the patient. [ABSTRACT FROM AUTHOR]

Two controlled trials of aromatherapy to decrease agitation in persons with dementia have recently produced promising results. However, both studies combined the use of essential oils with massage. Thus, it is unclear if the effect of the aromatherapy intervention was the result of smelling or the cutaneous absorption of the oils. The purpose of this study was to determine whether smelling lavender oil decreases the frequency of agitated behaviors in patients with dementia. Design: The study design was within-subjects ABCBA (A = lavender oil, B = thyme oil, C = unscented grapeseed oil): 4 weeks of baseline measurement, 2 weeks for each of the live treatment conditions (10-week total intervention time), and 2 weeks of postintervention measurement. Oil was placed every 3 hours on an absorbent fabric sachet pinned near the collarbone of each participant's shirt. Setting: A long-term care facility specifically for persons with dementia. Participants: Seven agitated nursing home residents with advanced dementia. Measurements: Agitation was assessed every 2 days using a modified Cohen-Mansfield Agitation Inventory. Olfactory functioning was assessed with structured olfactory identification and discrimination tasks, and with qualitative behavioral observation during those tasks. Results: Split-middle analyses conducted separately for each patient revealed no treatment effects specific to lavender, no weatment effects nonspecific to pleasant smelling substances, and no treatment effects dependent on order of treatment Administration. There were no differences between participants with more and less intact olfactory abilities. Conclusion: There is significant evidence in the neurologic and neuropsychologic literature that persons with dementia have impaired olfactory abilities. Concordant with this literature, this study kund no support kr the use of a purely olfactory form of aromatherapy to decrease agitation in severely demented patients. Cutaneous application of the essential oil may he necessary to achieve the effects reported in previous controlled studies. [ABSTRACT FROM AUTHOR]

Background Assisted living (AL) is the fastest growing segment of residential long-term care in the US. At least half of the estimated 1 million AL residents have dementia or cognitive impairment, with many AL facilities offering specialized dementia services. Little research has been done on the demographics, outcomes, or clinical variables of this population. Methods Participants were a cohort of 144 residents admitted to the AL unit of Copper Ridge, a specialized dementia-care facility. Comparison samples included 737 patients with dementia residing in other locations (home, nursing home, and other assisted living facilities). Selected measures of cognition, behavior, medical health, and function were taken at admission to AL and at 6-month intervals. Results When compared with residents of the dementia-specialized AL facility, dementia patients at home were younger, less cognitively impaired, and less likely to exhibit wandering, delusions, or aggression. Residents of a dementia-specialized nursing home had more cognitive impairment, greater medical comorbidity, and were more dependent on caregivers. The 2-year mortality rate in the dementia-specialized AL was 23%, significantly lower than rates reported for nursing homes. Primarily due to increasing care needs, most residents in the specialized AL relocated to a nursing home after a median stay of 10.9 months. Depression, falling, and wandering were significant predictors of the transition. Conclusion Dementia-specialized AL facilities occupy a unique position in the long-term care continuum that is distinct from home-care and nursing home facilities. This research is the first step toward understanding the significant dementia population residing in assisted living. Copyright © 2000 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]