Jeannie Marie S Leoutsakos

The Neuropsychiatric Inventory-Clinician rating scale (NPI-C): reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia

BACKGROUND Neuropsychiatric symptoms (NPS) affect almost all patients with dementia and are a major focus of study and treatment. Accurate assessment of NPS through valid, sensitive and reliable measures is crucial. Although current NPS measures have many strengths, they also have some limitations (e.g. acquisition of data is limited to informants or caregivers as respondents, limited depth of items specific to moderate dementia). Therefore, we developed a revised version of the NPI, known as the NPI-C. The NPI-C includes expanded domains and items, and a clinician-rating methodology. This study evaluated the reliability and convergent validity of the NPI-C at ten international sites (seven languages). METHODS Face validity for 78 new items was obtained through a Delphi panel. A total of 128 dyads (caregivers/patients) from three severity categories of dementia (mild = 58, moderate = 49, severe = 21) were interviewed separately by two trained raters using two rating methods: the original NPI interview and a clinician-rated method. Rater 1 also administered four additional, established measures: the Apathy Evaluation Scale, the Brief Psychiatric Rating Scale, the Cohen-Mansfield Agitation Index, and the Cornell Scale for Depression in Dementia. Intraclass correlations were used to determine inter-rater reliability. Pearson correlations between the four relevant NPI-C domains and their corresponding outside measures were used for convergent validity. RESULTS Inter-rater reliability was strong for most items. Convergent validity was moderate (apathy and agitation) to strong (hallucinations and delusions; agitation and aberrant vocalization; and depression) for clinician ratings in NPI-C domains. CONCLUSION Overall, the NPI-C shows promise as a versatile tool which can accurately measure NPS and which uses a uniform scale system to facilitate data comparisons across studies.

Predisposing factors for postoperative delirium after hip fracture repair in individuals with and without dementia.

Based on a multifactorial model of delirium, to compare the types and magnitude of pre‐ and intraoperative predisposing factors for incident delirium in a stratified sample of individuals with and without preoperative dementia undergoing acute hip fracture repair.

Effects of non-steroidal anti-inflammatory drug treatments on cognitive decline vary by phase of pre-clinical Alzheimer disease: findings from the randomized controlled Alzheimer's Disease Anti-inflammatory Prevention Trial.

We examined the effects of non‐steroidal anti‐inflammatory drugs on cognitive decline as a function of phase of pre‐clinical Alzheimer disease.

Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction

Mild cognitive impairment (MCI) is a syndrome thought to be a prodrome of dementia for some patients. One subtype, amnestic MCI (aMCI), may be specifically predispose patients to develop Alzheimers dementia (AD). Since dementia has been associated with a range of neuropsychiatric symptoms (NPS), we sought to examine the prevalence of NPS in MCI and its subtypes.

Outcomes of Early Delirium Diagnosis After General Anesthesia in the Elderly

BACKGROUND: Postoperative delirium in the elderly, measured days after surgery, is associated with significant negative clinical outcomes. In this study, we evaluated the prevalence and in-hospital outcomes of delirium diagnosed immediately after general anesthesia and surgery in elderly patients. METHODS: Consecutive English-speaking surgical candidates, aged 70 years or older, were prospectively enrolled during July to August 2010. After surgery, each participant was evaluated for a Diagnostic and Statistical Manual of Mental Disorders IV diagnosis of delirium in the postanesthesia care unit (PACU) and repeatedly thereafter while hospitalized. Delirium in the PACU was evaluated for an independent association with change in cognitive function from preoperative baseline testing and discharge disposition. RESULTS: Ninety-one (58% female) patients, 78% of whom were living independently before surgery, were found to have a prevalence of delirium in the PACU of 45% (41/91); 74% (14/19) of all delirium episodes detected during subsequent hospitalization started in the PACU. Early delirium was independently associated with impaired cognition (i.e., decreased category word fluency) relative to presurgery baseline testing (adjusted difference [95% confidence interval] for change in T-score: −6.02 [−10.58 to −1.45]; P = 0.01). Patients whose delirium had resolved by postoperative day 1 showed negative outcomes that were intermediate in severity between those who were never delirious during hospitalization and those whose delirium in the PACU persisted after transfer to hospital wards (adjusted probability [95% confidence interval] of discharge to institution: 3% [0%–10%], 26% [1%–51%], 39% [0%–81%] for the 3 groups, respectively). CONCLUSIONS: Delirium in the PACU is common, but not universal. It is associated with subsequent delirium on the ward, and potentially with a decline in cognitive function and increased institutionalization at hospital discharge.

A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease

Background: Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown. Objective: To assess DBS of memory circuits as a treatment for patients with mild Alzheimer’s disease (AD). Methods: We evaluated active “on” versus sham “off” bilateral DBS directed at the fornix-a major fiber bundle in the brain’s memory circuit-in a randomized, double-blind trial (ClinicalTrials.gov NCT01608061) in 42 patients with mild AD. We measured cognitive function and cerebral glucose metabolism up to 12 months post-implantation. Results: Surgery and electrical stimulation were safe and well tolerated. There were no significant differences in the primary cognitive outcomes (ADAS-Cog 13, CDR-SB) in the “on” versus “off” stimulation group at 12 months for the whole cohort. Patients receiving stimulation showed increased metabolism at 6 months but this was not significant at 12 months. On post-hoc analysis, there was a significant interaction between age and treatment outcome: in contrast to patients <65 years old (n = 12) whose results trended toward being worse with DBS ON versus OFF, in patients≥65 (n = 30) DBS-f ON treatment was associated with a trend toward both benefit on clinical outcomes and a greater increase in cerebral glucose metabolism. Conclusion: DBS for AD was safe and associated with increased cerebral glucose metabolism. There were no differences in cognitive outcomes for participants as a whole, but participants aged≥65 years may have derived benefit while there was possible worsening in patients below age 65 years with stimulation.

Longitudinal, region-specific course of diffusion tensor imaging measures in mild cognitive impairment and Alzheimer’s disease

Diffusion tensor imaging (DTI) is a promising method for identifying significant cross‐sectional differences of white‐matter tracts in normal controls (NC) and those with mild cognitive impairment (MCI) or Alzheimers disease (AD). There have not been many studies establishing its longitudinal utility.

Effects of general medical health on Alzheimer's progression: The Cache County Dementia Progression Study

BACKGROUND Several observational studies have suggested a link between health status and rate of decline among individuals with Alzheimers disease (AD). We sought to quantify the relationship in a population-based study of incident AD, and to compare global comorbidity ratings to counts of comorbid conditions and medications as predictors of AD progression. METHODS This was a case-only cohort study arising from a population-based longitudinal study of memory and aging, in Cache County, Utah. Participants comprised 335 individuals with incident AD followed for up to 11 years. Patient descriptors included sex, age, education, dementia duration at baseline, and APOE genotype. Measures of health status made at each visit included the General Medical Health Rating (GMHR), number of comorbid medical conditions, and number of non-psychiatric medications. Dementia outcomes included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating - sum of boxes (CDR-sb), and the Neuropsychiatric Inventory (NPI). RESULTS Health status tended to fluctuate over time within individuals. None of the baseline medical variables (GMHR, comorbidities, and non-psychiatric medications) was associated with differences in rates of decline in longitudinal linear mixed effects models. Over time, low GMHR ratings, but not comorbidities or medications, were associated with poorer outcomes (MMSE: β = -1.07 p = 0.01; CDR-sb: β = 1.79 p < 0.001; NPI: β = 4.57 p = 0.01). CONCLUSIONS Given that time-varying GMHR, but not baseline GMHR, was associated with the outcomes, it seems likely that there is a dynamic relationship between medical and cognitive health. GMHR is a more sensitive measure of health than simple counts of comorbidities or medications. Since health status is a potentially modifiable risk factor, further study is warranted.

Employment-based reinforcement of adherence to an FDA approved extended release formulation of naltrexone in opioid-dependent adults: A randomized controlled trial

BACKGROUND Naltrexone provides excellent opioid blockade, but its clinical utility is limited because opioid-dependent patients typically refuse it. An injectable suspension of naltrexone for extended release (XR-NTX) was recently approved by the FDA for treatment of opioid dependence. XR-NTX treatment may require concurrent behavioral intervention to maximize adherence and effectiveness, thus we sought to evaluate employment-based reinforcement as a method of improving adherence to XR-NTX in opiate dependent adults. METHODS Opioid-dependent adults (n=38) were detoxified and inducted onto oral naltrexone, then randomly assigned to contingency or prescription conditions. Participants received up to six doses of XR-NTX at four-week intervals. All participants could earn vouchers for attendance and performance at a therapeutic workplace. Contingency participants were required to accept XR-NTX injections to access the workplace and earn vouchers. Prescription participants could earn vouchers independent of their acceptance of XR-NTX injections. RESULTS Contingency participants accepted significantly more naltrexone injections than prescription participants (87% versus 52%, p=.002), and were more likely to accept all injections (74% versus 26%, p=.004). Participants in the two conditions provided similar percentages of samples negative for opiates (72% versus 65%) and for cocaine (58% versus 54%). Opiate positivity was significantly more likely when samples were also cocaine positive, independent of naltrexone blockade (p=.002). CONCLUSIONS Long-term adherence to XR-NTX in unemployed opiate dependent adults is low under usual care conditions. Employment-based reinforcement can maintain adherence to XR-NTX. Ongoing cocaine use appears to interfere with the clinical effectiveness of XR-NTX on opiate use.

History of manic and hypomanic episodes and risk of incident cardiovascular disease: 11.5 year follow-up from the Baltimore Epidemiologic Catchment Area Study

BACKGROUND While several studies have suggested that bipolar disorder may elevate risk of cardiovascular disease, few studies have examined the relationship between mania or hypomania and cardiovascular disease. The purpose of this study is to examine history of manic and hypomanic episodes as an independent risk factor for cardiovascular disease (CVD) during an 11.5 year follow-up of the Baltimore Epidemiologic Catchment Area Follow-up Study. METHODS All participants were psychiatrically assessed face-to-face based on Diagnostic Interview Schedule in 1981 and 1982 and were categorized as having either history of manic or hypomanic episode (MHE; n=58), major depressive episode only (MDE; n=71) or no mood episode (NME; n=1339). Incident cardiovascular disease (CVD; n=67) was determined by self-report of either myocardial infarction (MI) or congestive heart failure (CHF) in 1993-6. RESULTS Compared with NME subjects, the odds ratio for incident CVD among MHE subjects was 2.97 (95% confidence interval: 1.40, 6.34) after adjusting for putative risk factors. CONCLUSIONS These data suggest that a history of MHE increase the risk of incident CVD among community residents. Recognition of manic symptoms and addressing related CVD risk factors could have long term preventative implications in the development of cardiovascular disease in the community.