Neuropsychiatric Symptoms and Caregiver Burden in Individuals With Alzheimer's Disease: The TEAM-AD VA Cooperative Study.

OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms (NPS) in mild-to-moderate Alzheimer disease (AD) and their association with caregiver burden. METHODS: Secondary analyses of baseline data from the Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD) (N=613). Neuropsychiatric Inventory were used to measure severity of NPS and caregiver activity survey to measure caregiver burden. RESULTS: A total of 87% of patients displayed at least 1 NPS; 70% displayed clinically meaningful NPS. The most common symptoms were apathy (47%), irritability (44%), agitation (42%), and depression (40%). Those with moderate AD had more severe NPS than those with mild AD ( P = .03). Neuropsychiatric symptoms were significantly associated with caregiver time after adjusting for age, education, cognitive function, and comorbidity ( P-value < .0001) with every point increase in NPS associated with a 10-minute increase in caregiver time. CONCLUSION: Neuropsychiatric symptoms were prevalent in both mild and moderate AD, even in patients receiving treatment with an acetylcholinesterase inhibitors, and were more severe in moderate AD and associated with greater caregiver time.

Measuring informed consent capacity in an Alzheimer's disease clinical trial.

INTRODUCTION: Accurately and efficiently determining a participant's capacity to consent to research is critically important to protect the rights of patients with Alzheimer's disease (AD). METHODS: Understanding of the informed consent document was assessed in 613 community-dwelling patients with mild-to-moderate AD enrolled in a randomized, placebo-controlled trial. Associations were examined between clinically determined capacity to consent and (1) patient demographics and clinical characteristics and (2) the Informed Consent Questionnaire (ICQ), an objective measurement of a participant's factual understanding and perceived understanding. RESULTS: A total of 453 (74%) participants were determined to have capacity to consent by clinical judgment. ICQ perceived understanding, race, measures of cognitive function, and caregiver time were all significantly associated with the determination of capacity in multivariate analyses. DISCUSSION: We found a significant association between capacity and disease severity level, caregiver time, race, and ICQ perceived understanding.

Intermediate- and Long-Term Cognitive Outcomes After Cardiovascular Procedures in Older Adults: A Systematic Review.

BACKGROUND: Risks for intermediate- and long-term cognitive impairment after cardiovascular procedures in older adults are poorly understood. PURPOSE: To summarize evidence about cognitive outcomes in adults aged 65 years or older at least 3 months after coronary or carotid revascularization, cardiac valve procedures, or ablation for atrial fibrillation. DATA SOURCES: MEDLINE, Cochrane, and Scopus databases from 1990 to January 2015; ClinicalTrials.gov; and bibliographies of reviews and eligible studies. STUDY SELECTION: English-language trials and prospective cohort studies. DATA EXTRACTION: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and strength of evidence (SOE). DATA SYNTHESIS: 17 trials and 4 cohort studies were included; 80% of patients were men, and mean age was 68 years. Cognitive function did not differ after the procedure between on- and off-pump coronary artery bypass grafting (CABG) (n = 6; low SOE), hypothermic and normothermic CABG (n = 3; moderate to low SOE), or CABG and medical management (n = 1; insufficient SOE). One trial reported lower risk for incident cognitive impairment with minimal versus conventional extracorporeal CABG (risk ratio, 0.34 [95% CI, 0.16 to 0.73]; low SOE). Two trials found no difference between surgical carotid revascularization and carotid stenting or angioplasty (low and insufficient SOE, respectively). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement but had large selection and outcome measurement biases (insufficient SOE). LIMITATIONS: Mostly low to insufficient SOE; no pertinent data for ablation; limited generalizability to the most elderly patients, women, and persons with substantial baseline cognitive impairment; and possible selective reporting and publication bias. CONCLUSION: Intermediate- and long-term cognitive impairment in older adults attributable to the studied cardiovascular procedures may be uncommon. Nevertheless, clinicians counseling patients before these procedures should discuss the uncertainty in their risk for adverse cognitive outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Potentially suboptimal prescribing for older veteran nursing home patients with dementia.

BACKGROUND: Nursing home patients with dementia may be more likely to suffer adverse drug events from suboptimal prescribing. Previous studies have not used national samples, nor have they examined multiple types of suboptimal prescribing by dementia severity. OBJECTIVE: To examine the prevalence of and factors associated with potentially suboptimal prescribing in older veteran nursing home patients with dementia. METHODS: This is a retrospective descriptive study of 1303 veterans 65 years or older admitted between January 1, 2004, and June 30, 2005, with dementia for long stays (90+ days) to 133 Veterans Affairs Community Living Centers. Dementia severity was determined by the Cognitive Performance Scale and functional status dependences. RESULTS: Overall, 70.2% with mild-moderate dementia (n = 1076) had underuse because they did not receive an acetylcholinesterase inhibitor (AChEI), and 27.2% had evidence of inappropriate use because of a drug-disease or drug-drug-disease interaction. Of the 227 with severe dementia, 36.1% had overuse by receiving an AChEI or lipid-lowering or other agents, and 25.1% had evidence of inappropriate use as a result of a drug-disease or drug-drug interaction. Multinomial logistic regression analyses among those with mild to moderate dementia identified that living in the South versus other regions was the single factor associated with all 3 types of suboptimal prescribing. In those with severe dementia, antipsychotic use was associated with all 3 suboptimal prescribing types. CONCLUSIONS: Potentially suboptimal prescribing was common in older veteran nursing home patients with dementia. Clinicians should develop a heightened awareness of these problems. Future studies should examine associations between potentially suboptimal prescribing and health outcomes in patients with dementia.

Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial.

IMPORTANCE: Although vitamin E and memantine have been shown to have beneficial effects in moderately severe Alzheimer disease (AD), evidence is limited in mild to moderate AD. OBJECTIVE: To determine if vitamin E (alpha tocopherol), memantine, or both slow progression of mild to moderate AD in patients taking an acetylcholinesterase inhibitor. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, parallel-group, randomized clinical trial involving 613 patients with mild to moderate AD initiated in August 2007 and concluded in September 2012 at 14 Veterans Affairs medical centers. INTERVENTIONS: Participants received either 2000 IU/d of alpha tocopherol (n = 152), 20 mg/d of memantine (n = 155), the combination (n = 154), or placebo (n = 152). MAIN OUTCOMES AND MEASURES: Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL) Inventory score (range, 0-78). Secondary outcomes included cognitive, neuropsychiatric, functional, and caregiver measures. RESULTS: Data from 561 participants were analyzed (alpha tocopherol = 140, memantine = 142, combination = 139, placebo = 140), with 52 excluded because of a lack of any follow-up data. Over the mean (SD) follow-up of 2.27 (1.22) years, ADCS-ADL Inventory scores declined by 3.15 units (95% CI, 0.92 to 5.39; adjusted P = .03) less in the alpha tocopherol group compared with the placebo group. In the memantine group, these scores declined 1.98 units less (95% CI, -0.24 to 4.20; adjusted P = .40) than the placebo group's decline. This change in the alpha tocopherol group translates into a delay in clinical progression of 19% per year compared with placebo or a delay of approximately 6.2 months over the follow-up period. Caregiver time increased least in the alpha tocopherol group. All-cause mortality and safety analyses showed a difference only on the serious adverse event of "infections or infestations," with greater frequencies in the memantine (31 events in 23 participants) and combination groups (44 events in 31 participants) compared with placebo (13 events in 11 participants). CONCLUSIONS AND RELEVANCE: Among patients with mild to moderate AD, 2000 IU/d of alpha tocopherol compared with placebo resulted in slower functional decline. There were no significant differences in the groups receiving memantine alone or memantine plus alpha tocopherol. These findings suggest benefit of alpha tocopherol in mild to moderate AD by slowing functional decline and decreasing caregiver burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00235716.

Vitamin E and memantine in Alzheimer's disease: clinical trial methods and baseline data.

BACKGROUND: Alzheimer's disease (AD) has been associated with both oxidative stress and excessive glutamate activity. A clinical trial was designed to compare the effectiveness of (i) alpha-tocopherol, a vitamin E antioxidant; (ii) memantine (Namenda), an N-methyl-D-aspartate antagonist; (iii) their combination; and (iv) placebo in delaying clinical progression in AD. METHODS: The Veterans Affairs Cooperative Studies Program initiated a multicenter, randomized, double-blind, placebo-controlled trial in August 2007, with enrollment through March 2012 and follow-up continuing through September 2012. Participants with mild-to-moderate AD who were taking an acetylcholinesterase inhibitor were assigned randomly to 2000 IU/day of alpha-tocopherol, 20 mg/day memantine, 2000 IU/day alpha-tocopherol plus 20 mg/day memantine, or placebo. The primary outcome for the study is the Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory. Secondary outcome measures include the Mini-Mental State Examination; the Alzheimer's Disease Assessment Scale, cognitive portion; the Dependence Scale; the Neuropsychiatric Inventory; and the Caregiver Activity Survey. Patient follow-up ranged from 6 months to 4 years. RESULTS: A total of 613 participants were randomized. The majority of the patients were male (97%) and white (86%), with a mean age of 79 years. The mean Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory score at entry was 57 and the mean Mini-Mental State Examination score at entry was 21. CONCLUSION: This large multicenter trial will address the unanswered question of the long-term safety and effectiveness of alpha-tocopherol, memantine, and their combination in patients with mild-to-moderate AD taking an acetylcholinesterase inhibitor. The results are expected in early 2013.

Calcium and vitamin D supplementation and cognitive impairment in the women's health initiative.

OBJECTIVES: To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. DESIGN: Post hoc analysis of a randomized double-blind placebo-controlled trial. SETTING: Forty Women's Health Initiative (WHI) clinical centers across the United States. PARTICIPANTS: Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study. INTERVENTION: Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D(3) (treatment) and 2,109 to placebo. MEASUREMENTS: Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. RESULTS: Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71-1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72-1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups. CONCLUSION: There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.

Finding dementia in primary care: the results of a clinical demonstration project.

OBJECTIVES: To assess the effect of screening on diagnosing cognitive impairment. DESIGN: Quality improvement initiative. SETTING: Seven Veterans Affairs Medical Centers. PARTICIPANTS: Veterans aged 70 or older without a prior diagnosis of cognitive impairment. MEASUREMENTS: Veterans failing a brief cognitive screen (Mini-Cog score <4/5) at a routine primary care visit were offered a further, comprehensive evaluation with an advance practice registered nurse trained in dementia care and integrated into the primary care clinic. Veterans completing the evaluation were reviewed in a consensus conference and assigned a diagnosis of dementia; cognitive impairment, no dementia; or no cognitive impairment. Total numbers of screens, associated scores (0-5), and the consensus diagnoses were tallied. New cognitive impairment diagnoses were also tracked for veterans who passed the screen but requested further evaluation, failed but declined further evaluation, or were not screened. Primary care provider satisfaction with the program also was assessed. RESULTS: Of 8,342 veterans offered screening, 8,063 (97%) accepted, 2,081 (26%) failed the screen, 580 (28%) agreed to further evaluation, and 540 (93%) were diagnosed with cognitive impairment, including 432 (75%) with dementia. For screen passes requesting further evaluation, 87% (103/118) had cognitive impairment, including 70% (82/118) with dementia. Screen failures declining further evaluation had 17% (259/1,501) incident cognitive impairment diagnosed through standard care, bringing the total newly documented cognitive impairment in all screens to 11% (902/8,063), versus 4% (1,242/28,349) in similar clinics without this program. Eighty-two percent of primary care providers in clinics with this program agreed that it provided a useful service. CONCLUSION: Screening combined with offering further evaluation increased new diagnoses of cognitive impairment in older veterans two to three times. Veterans accepted screening well, and providers found the program useful.

Potential underuse, overuse, and inappropriate use of antidepressants in older veteran nursing home residents.

OBJECTIVES: To examine prevalence and resident- and site-level factors associated with potential underuse, overuse, and inappropriate use of antidepressants in older Veterans Affairs (VA) Community Living Center (CLC) residents. DESIGN: Longitudinal study. SETTING: One hundred thirty-three VA CLCs. PARTICIPANTS: Three thousand six hundred ninety-two veterans aged 65 and older admitted between January 1, 2004, and June 3, 2005, with long stays (≥ 90 days). MEASUREMENTS: Prevalence of potential underuse, inappropriate use, and overuse of antidepressants in residents with and without depression (as documented according to International Classification of Diseases, Ninth Revision, Clinical Modification, codes or Depression Rating Scale). RESULTS: Selective serotonin reuptake inhibitors were the most commonly prescribed antidepressant. Of the 877 residents with depression, 25.4% did not receive an antidepressant, suggesting potential underuse. Of residents with depression who received antidepressants, 57.5% had potential inappropriate use due primarily to problems seen with drug-drug and drug-disease interactions. Of the 2,815 residents who did not have depression, 1,190 (42.3%) were prescribed one or more antidepressants; only 48 (4.0%) of these had a Food and Drug Administration-approved labeled indication, suggesting potential overuse. Overall, only 17.6% of antidepressant use was appropriate (324/1,844). The only consistent resident factor associated with potential underuse and overuse use was taking an antipsychotic without evidence of schizophrenia (underuse: adjusted relative risk ratio (ARRR)=0.56, 95% confidence interval (CI)=0.33-0.94; overuse: adjusted odds ratio=1.52, 95% CI=1.21-1.91). Having moderate to severe pain (ARRR=1.54, 95% CI=1.08-2.20) and the prescribing of an anxiolytic or hypnotic (ARRR=1.33, 95% CI=1.02-1.74) increased the risk of potential inappropriate antidepressant use. CONCLUSION: Potential problems with the use of antidepressants were frequently observed in older U.S. veteran CLC residents. Future studies are needed to examine the true risks and benefits of antidepressant use in CLC and non-VA nursing homes.

Are all commonly prescribed antipsychotics associated with greater mortality in elderly male veterans with dementia?

OBJECTIVES: To estimate mortality risk associated with individual commonly prescribed antipsychotics. DESIGN: Five-year retrospective study. SETTING: Veterans national healthcare data. PARTICIPANTS: Predominantly male, aged 65 and older, with a diagnosis of dementia and no other indication for an antipsychotic. Subjects who received an antipsychotic were compared with randomly selected controls who did not. Exposed and control cohorts were matched according to their date of dementia diagnosis and time elapsed from diagnosis to the start of antipsychotic therapy. MEASUREMENTS: Mortality during incident antipsychotic use. RESULTS: Cohorts who were exposed to haloperidol (n=2,217), olanzapine (n=3,384), quetiapine (n=4,277), or risperidone (n=8,249) had more comorbidities than their control cohorts. During the first 30 days, there was a significant increase in mortality in subgroups prescribed a daily dose of haloperidol greater than 1 mg (hazard ratio (HR)=3.2, 95% confidence interval (CI)=2.2-4.5, P<.001), olanzapine greater than 2.5 mg (HR=1.5, 95% CI=1.1-2.0, P=.01), or risperidone greater than 1 mg (HR=1.6, 95% CI=1.1-2.2, P=.01) adjusted for demographic characteristics, comorbidities, and medication history using Cox regression analyses. Greater mortality was not seen when a daily dose of quetiapine greater than 50 mg (HR=1.2, 95% CI=0.7-1.8, P=.50) was prescribed, and there was no greater mortality associated with a dose less than 50 mg (HR=0.7, 95% CI=0.5-1.0, P=.03). No antipsychotic was associated with greater mortality after the first 30 days. CONCLUSION: Commonly prescribed doses of haloperidol, olanzapine, and risperidone, but not quetiapine, were associated with a short-term increase in mortality. Further investigations are warranted to identify patient characteristics and antipsychotic dosage regimens that are not associated with a greater risk of mortality in elderly patients with dementia.

Fluorodeoxyglucose positron emission tomography of mild cognitive impairment with clinical follow-up at 3 years.

BACKGROUND: Alzheimer's disease (AD) is the most common dementing illness. Development of effective treatments directed at AD requires an early diagnosis. Mild cognitive impairment (MCI) often heralds AD. Thus, characterizing MCI is fundamental to the early diagnosis of AD. METHODS: 19 MCI patients referred from a memory loss clinic and 27 healthy subjects, all followed up for 3 years. Metabolism scans (MCI minus controls) were compared voxel-wise after anatomic normalization and were examined both visually and with a computerized classifier. RESULTS: Agreement between raters as to whether the individual scans were normal or abnormal was high. Agreement between raters of the eventual clinical diagnosis and baseline metabolic pattern was poor. A computerized classifier was unsuccessful at classifying MCI from normal; however, its performance improved when using only prototypic AD-like MCI scans, indicating the classifier worked well when shared patterns existed in the data. Outcomes on follow-up were nine of 19 AD, five of 19 remained MCI, and five of 19 developed dementias other than AD. Both MCI cases of early Lewy body dementia (LBD) showed an AD-like metabolic pattern. CONCLUSIONS: Visual inspection proved reliable in determining normal from abnormal scans, but it proved unreliable at predicting diagnosis on follow-up. Computerized classification of MCI by using an AD-like metabolic template (such as derived from the averaged MCI images) showed potential to identify patients who will develop AD. However, the metabolic pattern in early LBD did not differ from that in AD.

Changes in vitamin E prescribing for Alzheimer patients.

OBJECTIVE: At the end of 2006, a survey was sent to members of the American Association of Geriatric Psychiatry (AAGP) to assess possible changes in prescribing Vitamin E to patients with Alzheimer disease that followed two published reports in early 2005 suggesting increased mortality and an increased incidence of heart failure with Vitamin E supplements. METHOD: A three-item questionnaire was mailed to all AAGP members who had prescription privileges to assess changes in prescribing Vitamin E after January, 2005. RESULTS: A total of 572 completed surveys were returned for a response rate of 35%. Nearly 60% of respondents reported a change over the 2 years that followed the 2005 reports. The greatest change was in the group not prescribing Vitamin E, which increased from 6.6% before 2005 to 60.6% afterward. CONCLUSIONS: AAGP members significantly reduced prescribing Vitamin E to patients with Alzheimer disease after 2005. The two reports are discussed with an emphasis on their methodological limitations and the potential for additional information on Vitamin E side effects from ongoing research.

Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging.

Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown.

Dementia and Alzheimer's disease in community-dwelling elders taking vitamin C and/or vitamin E.

BACKGROUND: Since increased oxidative stress may impair cognition and be a risk factor for dementia, there has been interest in determining whether use of antioxidants could protect against such events. OBJECTIVE: To determine whether supplement use of vitamins C and/or E in a community-based sample of older African American and white individuals delayed incident dementia or Alzheimer's disease (AD). METHODS: We selected a subgroup from the Duke Established Populations for Epidemiologic Studies of the Elderly, a longitudinal study of community-representative persons aged 65-105 years living in 5 adjacent counties in North Carolina, and followed them for dementia (1986-1987 through June 2000). Information gathered during in-home interviews included sociodemographic characteristics, health status, health service use, and vitamin use. Diagnosis of dementia and AD was based on evaluations using the clinical and neuropsychological batteries of the Consortium to Establish a Registry for Alzheimer's Disease, with final determination by consensus agreement of specialists using Diagnostic and Statistical Manual of Mental Disorders, third revision, and National Institute for Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders criteria. RESULTS: Of 616 persons initially dementia-free (mean age 73 y; 62% female; 62% African American), 141 developed dementia, of whom 93 developed AD. Increased age and mobility problems were risk factors for dementia (only age for AD), while an increased number of outpatient visits reduced the likelihood of developing dementia. Neither use of any vitamins C and/or E (used by 8% of subjects at baseline) nor high-dose use reduced the time to dementia or AD. CONCLUSIONS: In this community in the southeastern US where vitamin supplement use is low, use of vitamins C and/or E did not delay the incidence of dementia or AD.

Comparison of olanzapine and risperidone in the treatment of psychosis and associated behavioral disturbances in patients with dementia.

OBJECTIVE: The authors compared efficacy of olanzapine versus placebo and risperidone as measured by the Neuropsychiatric Inventory and Clinical Global Impression-Severity of Psychosis scale in patients with dementia-related psychosis. METHODS: Patients with moderate-to-severe psychotic symptoms associated with dementia were recruited from outpatient or residential settings and randomly assigned to 10-week, double-blind, flexible-dose treatment with olanzapine (N=204; 2.5 mg-10 mg/day; mean: 5.2 mg/day), risperidone (N=196; 0.5 mg-2 mg/day; mean: 1.0 mg/day) or placebo (N=94). RESULTS: Most measures of neuropsychiatric functioning improved in all treatment groups, including the placebo group, and no significant treatment differences occurred. Overall discontinuation was lowest in the placebo group, and the olanzapine group had a significantly higher incidence of discontinuation due to adverse events (16.2%) relative to placebo (3.2%) and risperidone (8.7%) groups. Treatment-emergent extrapyramidal symptoms were more numerous for risperidone- than placebo- or olanzapine-treated patients. Abnormally high prolactin levels occurred in 78.0% of risperidone patients, compared with 16.7% for olanzapine and 5.0% for placebo. The incidence of weight gain greater than 7% from baseline was higher in the olanzapine group relative to risperidone, but neither active-treatment group showed a statistical difference from placebo (1.1%). No other statistically significant and clinically relevant differences were seen for any other vital sign, electrocardiographic measure, or laboratory hematology and chemistry, including glucose, except for cholesterol, which decreased from baseline to endpoint in both active-treatment groups. CONCLUSIONS: Patients' neuropsychiatric functioning improved with olanzapine, risperidone, and placebo treatment. There was a substantial response in the placebo group, and no significant differences emerged among treatments.

The effect of tau genotype on clinical features in FTDP-17.

The clinical phenotype of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) varies. This variability is seen not only between kindreds with different mutations but also in families sharing the same mutation. Inheritance of tau haplotype (H1) and genotype (H1/H1) has been established as a risk factor for some neurodegenerative disorders with parkinsonism. We assessed the effect of tau polymorphism on the clinical features of FTDP-17 in 61 cases from 30 separately ascertained families with four different tau mutations, including P301L, +16, N279K, and P301S. There were no significant differences of age at symptomatic onset and disease duration between H1/H1 and H1/H2 genotypes. The comparison between tau genotype and type of initial clinical sign showed an association between the H1/H1 genotype and parkinsonian phenotype and between the H1/H2 genotype and frontotemporal dementia phenotype (OR=11.7; 95% confidence interval, 1.4-98.7; P=0.008). Our results suggest that tau genotype does not influence the disease course. However, it may predispose to a specific clinical sign in the early stage of FTDP-17.

Recidivism in medication-noncompliant serious juvenile offenders with bipolar disorder.

OBJECTIVE: To determine whether the recidivism rate varies for adolescent serious juvenile offenders with bipolar disorder in response to compliance with antimanic medication. METHOD: Probation records were reviewed for all adolescents (N = 31) released during a 1-year period (April 1, 1993-March 31, 1994) from a county juvenile corrections treatment facility who had DSM-III-R bipolar disorder, were stabilized on medication, and had agreed to continue treatment at an adolescent psychiatry clinic. New offenses and probation violations committed during the 12-month period after release were tallied. These recidivism records were then compared with medical records to ascertain whether these acts were committed while subjects were on (taking) or off (not taking) medication. RESULTS: The number of serious offenses (felonies and misdemeanors) was significantly reduced while subjects were on medication (4 offenses in 2992 days) versus off medication (39 offenses in 6108 days) (p < .0001). The off-medication rate of offending was 4.8 times higher than the on-medication rate. Probation violations were also significantly reduced while subjects were on medication (p < .001). CONCLUSION: Compliance with prescribed antimanic medication can markedly decrease recidivism in serious juvenile delinquents with bipolar disorder.

The Driver With Dementia: A Review of the Literature.

The authors review 10 studies of driving and dementia. They found poor agreement among the researchers with regard to the stage at which a patient with dementia should discontinue driving and the appropriate tools to be used for an assessment of driving skills. They make recommendations for a comprehensive driving assessment and for the clinical management of drivers with dementia. Because the impaired driver is a medical as well as a public safety concern, clinicians and policymakers must work together to address the many problems associated with this issue.