Internalize at your peril: internalizing disorders as risk factors for dementia-cohort study.

Few studies examined comorbid anxiety and depression's independent association with dementia. We assessed internalizing disorders as risk factors for dementia to avoid pitfalls inherent in separating anxiety and depression. Retrospectively designed prospective comparative cohort study using New Zealand's (NZ) National Minimum Dataset of hospital discharges. Hazards ratios (HRs), estimated from parametric survival models, compared the time to incident dementia after a minimal latency interval of 10 years between those with and without prior diagnosis of an internalizing disorder. A total of 47,932 patients aged 50-54 years were discharged from a publicly funded hospital events in NZ between 1988 and 1992. Of these, 37,631 (79%) met eligibility criteria, and incident dementia was diagnosed in 1594. Rates of incident dementia were higher among patients with an earlier diagnosis of internalizing disorders (572 vs 303 per 100,000 person years at risk (PYAR)). After adjustment for age, sex, ethnicity, and region, those with internalizing disorders were estimated to have a higher risk of developing dementia than those without (adjusted HR = 1.57, 95% CI 1.17-2.10). Females with an earlier diagnosis of internalizing disorders were estimated to have almost twice the risk of developing dementia (adjusted HR 1.80, 95% CI 1.25-2.59). Internalizing disorders affect one in five adults globally. Our findings suggest a significant increase in risk of dementia more than 10 years after the diagnosis of internalizing disorder.

Two Ethnic Clusters with Huntington Disease in Israel: The Case of Mountain Jews and Karaites.

BACKGROUND: Worldwide prevalence estimates of Huntington disease (HD) vary widely, with no reliable information regarding the Jewish population in Israel. METHODS: This specialized tertiary single-center cross-sectional study assessed clinical, cognitive, and demographic characteristics of 84 HD patients who were treated at the Movement Disorder Unit of the Tel Aviv Medical Center, Israel. RESULTS: Our cohort was composed of one-third Ashkenazi Jews, 27% Mountain Jews (Caucasus Jews), 18% Sephardi Jews, and 21% Karaites, with both Mountain Jews and Karaites over-represented compared to their relevant proportion in the population of the state of Israel, which is less than 1%. No between-group differences were detected regarding the number of CAG (cytosine-adenine-guanine) repeats, age at onset, disease duration, years from symptom onset to diagnosis, gender, years of education, Unified Huntington Disease Rating Scale scores, or the Montreal Cognitive Assessment scores. CONCLUSION: We detected clustering of HD among the population treated at our Medical Center, which has the only specialized HD clinic in the country, with a high percentage of HD among 2 relatively small subpopulations of Jews: Mountain Jews and Karaites.

Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: An-Open Label, Add-On, Pilot Study.

BACKGROUND: Tetrahydrocannabinol (THC) is a potential treatment for Alzheimer's disease (AD). OBJECTIVE: To measure efficacy and safety of medical cannabis oil (MCO) containing THC as an add-on to pharmacotherapy, in relieving behavioral and psychological symptoms of dementia (BPSD). METHODS: Eleven AD patients were recruited to an open label, 4 weeks, prospective trial. RESULTS: Ten patients completed the trial. Significant reduction in CGI severity score (6.5 to 5.7; p <  0.01) and NPI score were recorded (44.4 to 12.8; p <  0.01). NPI domains of significant decrease were: Delusions, agitation/aggression, irritability, apathy, sleep and caregiver distress. CONCLUSION: Adding MCO to AD patients' pharmacotherapy is safe and a promising treatment option.

Escitalopram versus risperidone for the treatment of behavioral and psychotic symptoms associated with Alzheimer's disease: a randomized double-blind pilot study.

BACKGROUND: Antipsychotics are frequently used to treat psychosis, aggression and agitation in patients with Alzheimer's disease (AD), but safety warnings abound. Escitalopram was investigated since citalopram has demonstrated some effectiveness in AD. We compared escitalopram and risperidone for psychotic symptoms and agitation associated with AD. METHODS: Inpatients with AD, who had been hospitalized because of behavioral symptoms, were recruited to a six-week randomized, double-blind, controlled trial. Participants (n = 40) were randomized to once daily risperidone 1 mg or escitalopram 10 mg. RESULTS: The NPI total score improved in both groups. Onset was earlier in the risperidone-treated group, but improvement did not significantly differ between groups by study end. Completion rates differed for escitalopram (75%) and risperidone (55%), mainly due to adverse events. There were no adverse events in the escitalopram group, while in the risperidone group two patients suffered severe extrapyramidal symptoms and four patients suffered acute physical illness necessitating transfer to general hospital. CONCLUSION: Escitalopram and risperidone did not differ in efficacy in reducing psychotic symptoms and agitation in patients with AD. Completion rates were higher for escitalopram-treated patients. Replication in larger trials with ambulatory patients is needed.

Quetiapine augmentation of antidepressant treatment in elderly patients suffering from depressive symptoms: a retrospective chart review.

Depression in elderly patients is often characterized by poor responses to standard antidepressants. Several reports have suggested that quetiapine also may have antidepressant properties. The present study aimed to evaluate the efficacy of quetiapine augmentation in depressed elderly patients previously unresponsive to a full course of treatment. Medical charts of elderly depressed inpatients treated at a tertiary care psychiatric center during a 3-year period were reviewed. Clinical and demographic data were extracted from computerized records and analyzed. The primary outcome measure was the change on the clinical global impressions scale for improvement (CGI-I). Twenty depressed elderly inpatients received quetiapine augmentation during the study period. Prior to augmentation all had been treated with antidepressants. Baseline mean severity of depression was 6.40; severity after augmentation was significantly reduced to 3.25; the change in CGI-I was 2.10 (p<0.03). Mean quetiapine dose was 70 mg; mean duration of augmentation was 3.9 weeks. Five patients complained of somnolence. One patient discontinued psycho-tropics and switched to electroconvulsive therapy (ECT) due to life-threatening suicidal tendencies. We tentatively conclude that quetiapine augmentation for elderly depressed patients unresponsive to standard antidepressant treatment may be a safe and efficacious option. Further prospective studies need be carried out to support our observation.

Narcolepsy and psychotic states--a case report.

Narcolepsy is characterized by symptoms that include excessive sleepiness during the daytime, cataplexy, hypnagogic hallucinations and sleep paralysis. We present a single unusual case report of a patient who was admitted to a psychiatric facility. A 20-year-old single woman was hospitalized in a general hospital due to involuntary movements in her limbs. Following complaints of continual daily sleepiness and instances of a loss of muscle tone she was referred for sleep assessment. The patient was diagnosed with narcolepsy and cataplexy. Later, due to auditory hallucinations she was referred to a psychiatric hospital. Her reality judgement was poor, with partial insight regarding her illness. The patient was treated with methylphenidate 20 mg/day and antipsychotic medication; risperidone of up to 4 mg/day, and paroxetine 20 mg/day to prevent cataplexy. Following further exacerbation, pharmacotherapy was changed to risperidone 6 mg/day and modafinil 200 mg/day. This treatment led to a significant improvement in her condition. The report presented here suggests that combined treatment with a psycho-stimulant drug, an SSRI in combination with antipsychotic treatment, may be indicated in narcolepsy with cataplexy and vivid psychotic production. Multidisciplinary cooperation of neurologists and psychiatrists enabled this therapy to be administered for the patient's benefit.

Quetiapine for elderly non-responsive schizophrenia patients.

Ten elderly chronic schizophrenia patients who were not responding to an atypical antipsychotic were switched to quetiapine. The Brief Psychiatric Rating Scale (BPRS) demonstrated statistically significant improvement after 6 months of quetiapine treatment. Four patients discontinued treatment due to clinical exacerbation or sedation. There was no increase in abnormal movements or body weight.

Effects of pharmacological therapy on gait and cognitive function in depressed patients.

OBJECTIVE: To investigate the relationship among affective status, cognitive function, and gait in depressed patients and to evaluate the effects of treatment of depression on gait and cognitive function. METHODS: Nineteen patients recently diagnosed with clinical depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) were recruited from a psychiatric outpatient clinic. Evaluation included the Hamilton Depression Rating Scale (HAM-D), the Mini-Mental State Examination, a computerized neuropsychological battery (Mindstreams, NeuroTrax Corp, New York, NY), and Barthel's Index of Instrumental Activities of Daily Living. Temporal parameters of gait were quantified using a stopwatch and force-sensitive insoles. All assessments were performed at baseline and after approximately 10 weeks of treatment with antidepressants. RESULTS: The patients' mean age was 68.6 +/- 9.1 years (15 women). Therapy significantly (P < 0.001) improved the affective state (HAM-D scores). There were small but significant improvements in gait speed (P = 0.033), stride time variability (P = 0.036), and gait asymmetry (P = 0.038). With the exception of the hand-eye coordination index, all tested cognitive domains also improved significantly. Baseline depression scores correlated with changes in depression: patients with higher HAM-D scores at baseline had more significant improvement in their affect (P < 0.001). Changes in HAM-D were not significantly correlated with changes in gait or changes on computerized tests of cognitive function (P > 0.10). CONCLUSIONS: Depressive symptoms are associated with gait and cognitive impairment. Moreover, the present results suggest that these domains improve in response to antidepressant medication.

Cardiac and cerebrovascular morbidity and mortality associated with antipsychotic medications in elderly psychiatric inpatients.

OBJECTIVE: To evaluate the rate of adverse medical outcomes for elderly exposed to antipsychotic treatment. METHODS: This was a retrospective evaluation of psychiatric inpatients records. Age, gender, diagnosis, treatment with antipsychotics, and duration of treatment were analyzed. An acute cardiac or cerebrovascular event necessitating transfer to a general hospital or resulting in death was the outcome measure. RESULTS: During 15 years (1990 to 2005), 3,111 elderly were hospitalized. Their mean age was 73.5 +/- 6.1 years, 1,220 were male (39%), and 1,891 were female (61%). Most patients (2,583 [83%]) were exposed to antipsychotics, of which 1,402 (54%) were exposed to second-generation antipsychotics (SGAs). Antipsychotic-treated patients did not have a higher rate of adverse medical outcomes compared with patients who had not received antipsychotics. No significant differences were noted between patients exposed to typical antipsychotics or SGAs. CONCLUSION: Treatment of elderly psychiatric inpatients with antipsychotics did not increase their risk of adverse medical outcomes. Thus, regulating the use of conventional antipsychotics or SGAs for all elderly patients in all indications may be premature.

Tetrabenazine in the treatment of Huntington's disease.

Tetrabenazine (TBZ), a catecholamine-depleting agent initially developed for the treatment of schizophrenia, when tested for other indications, has proven to be more useful for the treatment of a variety of hyperkinetic movement disorders. These disorders include neurological diseases characterized by abnormal involuntary movements such as chorea associated with Huntington's disease, tics in Tourette's syndrome, dyskinesias and dystonias in tardive dyskinesia, also primary dystonias and myoclonus. This review will include and discuss studies published during the period of 1960-2006 regarding the clinical efficacy and tolerability of TBZ in Huntington's disease (HD). It will also review the chemistry, pharmacokinetics and dynamics of the drug and its mechanism of action compared to that of reserpine, the only similar compound. This review emphasizes the advantage of TBZ over dopamine-depleting compounds used in the treatment of chorea and reveals its clinical efficacy and side effects.

Effect of dopamine agonists on fatigue and somnolence in Parkinson's disease.

Dopamine agonists are becoming increasingly important in the treatment of early and advanced symptoms of Parkinson disease (PD). Although dopamine agonists are known to increase somnolence, their effect on fatigue and the relationship between fatigue and somnolence have not been investigated thoroughly. The objective of this study is to quantitatively measure fatigue in patients with PD treated with dopamine agonists and to correlate fatigue with somnolence. Fifteen patients with PD (mean age, 60.6 +/- 9.7 years; mean disease duration, 4.1 +/- 1.9 years) underwent a continuous (30-second) motor task using four muscle groups before and after 3 months of treatment with dopamine agonists. A fatigue index, defined as the decay of maximal force during continuous exercise, was calculated. Findings were compared with 15 healthy, age-matched control subjects. Patients also completed the Multidimensional Fatigue Inventory (MFI), the Epworth Sleepiness Scale (ESS), and the Hamilton Depression Scale at the same time points. Mean fatigue index (FI) before treatment was significantly higher in PD patients than controls (31.37% +/- 3.81% vs. 23.39% +/- 3.03%, P < 0.001). There was no significant between-group difference after 3 months of treatment. There was no difference in FI of the more affected side before and after treatment (33.33% +/- 6.18% vs. 34.08% +/- 5.43%, P > 0.1). No significant change in MFI scores were noted after treatment, although scores on the ESS increased significantly (6.6 +/- 2.63 vs. 11.7 +/- 5.16; P < 0.05). Fatigue is prevalent in patients with PD but is not influenced by dopamine agonists. Somnolence cannot be attributed to the increase in fatigability and apparently involves a different mechanism.

Association between family history of dementia and hallucinations in Parkinson disease.

OBJECTIVE: To identify familial risk factors for hallucinations in patients with Parkinson disease (PD). METHODS: Two hundred seventy-six outpatients with PD participated in the study. The presence of hallucinations was determined using a validated questionnaire, including items regarding the occurrence of visual, auditory, or other types of hallucinations. Family history of PD and dementia was determined by a structured interview and examination of medical records and affected family members. Patients with young-onset PD (<50 years) who reported another PD patient among their siblings were tested for parkin mutations. Stepwise logistic regression was applied for the detection of risk factors. The regression model included a set of family history-related variables (family history of PD and of dementia) and a set of disease-related variables (age, age at onset of PD, stage, duration of PD and of l-dopa therapy, l-dopa dose, and number of antiparkinsonian drugs). RESULTS: Hallucinations were present in 32% of the 276 patients. Risk factors for hallucinations included Mini-Mental State Examination score (p < 0.0001) and positive family history of dementia (p = 0.0005). CONCLUSION: Family history of dementia and lower Mini-Mental State Examination scores are risk factors for hallucinations in Parkinson disease.

Donepezil for the treatment of behavioral symptoms in patients with Alzheimer's disease.

Behavioral and psychologic symptoms of dementia (BPSD) are common manifestations in mid- and late-stage Alzheimer's disease (AD). Traditional treatments for BPSD are neuroleptics and sedatives, which are not devoid of serious adverse effects. A number of studies show beneficial effects in the treatment of BPSD with acetylcholinesterase inhibitors (AChEI). The present study aimed to evaluate the effect of donepezil (using the generic drug Memorit) as monotherapy for AD patients suffering from BPSD. Twenty-eight consecutive patients followed at the Memory Outpatient Clinic and Psychogeriatric Department of the Abarbanel Mental Health Center were treated with donepezil for 6 months. Starting dose was 5 mg daily during the first 4 weeks and continuation with 10 mg daily thereafter. Treatment effects were evaluated using the Mini Mental State Examination (MMSE), the Neuro-Psychiatric Inventory (NPI), and the Clinical Global Impression of Change Scale (CGIC) caregiver version. Twenty-four of 28 patients completed the study. Of these, five patients needed additional rescue neuroleptic treatment due to incomplete response. The mean dose of donepezil was 9.10 mg/day (median 10 mg/day). The overall NPI improved significantly from 33.4 to 21.2 (p = 0.008). The mean CGIC at study's end was 3.0 (mild improvement). The cognitive scores did not change significantly. When compared to the patients who completed the study, patients who discontinued had higher mean scores on the irritability and agitation subscales of the NPI, they were older, and they had longer disease duration and lower MMSE mean scores. Three adverse events were recorded: one syncope causing a toe phalanx fracture and gastrointestinal complaints that resolved over time in two additional patients. Acetylcholinesterase inhibitors should be considered for the treatment of BPSD before neuroleptic treatment is instituted in AD patients with low levels of irritability and agitation.