Diana Paleacu

Risk factors for dementia, depression and psychosis in long-standing Parkinson's disease

Summary.Objectives. To study the relationships between clinical features of Parkinsons disease (PD) and the development of dementia, depression or psychosis in patients with long-standing disease. Background. The natural history of dementia and depression in PD, and its relation to psychosis in long standing PD, are unclear. Method. 172 consecutive patients (99 men and 73 women, mean age at symptoms onset 58.3 ± 13.2 years) with 5 years or more of PD (mean symptom duration of 11.8 ± 5.6 years) were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patient charts and outside documents. Dementia and depression were diagnosed according to DSM-IV criteria, while psychosis was diagnosed if hallucinations or delusions were present. Chi-square and t tests were used to compare the patient characteristics among those with vs. those without mental complications of the disease at different disease stages. Logistic regression was used for the comparison of associations between the presence of dementia or depression (dependent variable) and age at onset of PD, duration of PD and disease staging (explanatory variables). Results. The study population consisted of 45 patients at Hoehn & Yahr (H&Y) stage ≤2.5 (26%), 104 patients at stage 3 (60.5%) and 23 patients at H&Y stage 4–5 (13.5%). Sixty one patients (36%) had dementia, 55 patients had depression (33%) and 50 patients (27%) had psychosis. Dementia and depression were significantly associated with disease severity as reflected in the H&Y scale (P = 0.0003, Z = 3.59; P = 0.006, Z = 3.22, respectively). These associations were significant also for the older age of PD onset (≥59 years n = 89) subgroup (p = 0.001, Z = 3.2 for dementia and p = 0.02, Z = 2.9 for depression), but not for younger onset cases (<59 years n = 83). Dementia was significantly associated with older age of PD onset (β = 0.04, p = 0.009) while depression was inversely associated with age of PD onset (β = −0.04, p = 0.02). The presence of dementia was also significantly associated with depression (β = 1.49, p = 0.0006). Dementia and depression were found to be independent explanatory variables for the development of psychosis (logistic regression, odds ratio (OR) = 26.0, p < 0.0001; OR = 10.2, p < 0.0001, respectively). In patients with younger age of PD onset, depression more than dementia was strongly correlated with the appearance of psychosis. Conclusion. Dementia in PD was related to older age of symptoms onset and old age. Depression was associated with dementia or early age of PD onset. Depression seemed to contribute to the appearance of psychosis even more than dementia, especially in patients with younger age of symptoms onset.

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 Alzheimers 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 studys 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.

Re: The apolipoprotein E epsilon4 allele increases the risk of drug-induced hallucinations in Parkinson's disease.

: To determine whether the apolipoprotein E (APOE) epsilon 4 allele is a risk factor of drug-induced hallucinations in nondemented patients with Parkinsons disease (PD), the proportions of patients with hallucinations in groups with and without the APOE epsilon 4 allele were compared with a chi 2 test. The contribution of the APOE epsilon 4 allele to the occurrence of hallucinations was further evaluated by means of logistic regression models, adjusting for potential prognostic variables. Thirteen (76%) of the 17 patients who had the epsilon 4 allele had visual hallucinations, compared with 20 (23%) of the 88 patients without the epsilon 4 allele (p < 0.0001; odds ratio = 11.05; 95% CI 3.24-37.67). In addition, treatment with dopamine agonists also contributed to an increased risk of hallucinations (p = 0.0011). After adjustment for age, severity of parkinsonism, duration of treatment, dose of levodopa, and treatment with dopamine agonists, the association between the presence of the epsilon 4 allele and the occurrence of visual hallucinations remained significant (p = 0.0003). Nondemented PD patients with the APOE epsilon 4 allele have a high risk of developing drug-induced visual hallucinations. Further studies are needed to evaluate which proportion of these patients will end up developing dementia.

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 Alzheimers 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.

Donepezil for negative signs in elderly patients with schizophrenia: an add-on, double-blind, crossover, placebo-controlled study

OBJECTIVE Cognitive impairment and negative signs are common in patients with schizophrenia. Up to 35% of elderly patients with schizophrenia fulfill the diagnostic criteria of dementia. Donepezil inhibits cholinesterase, thus enhancing cholinergic neurotransmission. We tested the efficacy of donepezil in elderly patients with chronic schizophrenia and severe cognitive impairment. METHOD Following baseline assessment, patients were randomly assigned to receive either donepezil or placebo. The dose was 5 mg daily for the first week and 10 mg for an additional 11 weeks. The procedure was repeated using the crossover compound. The Positive and Negative Symptom Scale (PANSS), Clinical Global Impression Scale (CGI) and Alzheimer Disease Assessment Scale - Cognitive subscale (ADAS-Cog) were used to assess the severity of symptoms, cognitive status and intervention effects. RESULTS Twenty subjects were enrolled (15 females, five males), mean age 70.2 years (SD 6.5) and mean duration of disease 38.5 years (SD 9.3). A modest treatment effect was found for both placebo and donepezil treatment periods. No crossover effect was found. No statistical differences were demonstrated between the two treatment groups (CGI p = 0.37, PANSS p = 0.71, ADAS-Cog p = 0.86). Two patients died during the study period due to unrelated causes and one patient discontinued participation due to increased agitation. CONCLUSION Donepezil does not seem to improve negative signs and cognitive impairment in elderly patients with chronic schizophrenia.

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.

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.

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.

Apolipoprotein E ε4 Allele Does Not Influence the Development of Dementia in Parkinsonian Patients

James Parkinson in 1817 in his famous Essay on the Shaking Palsy described the “involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forwards, and to pass from a walking to a running pace: the senses and intellects being uninjured” (Parkinson, 1817). Indeed the possibility that PD is associated with dementia has been negated by neurologists for several decades. It should be mentioned that antedating levodopa therapy patients could not be formally cognitively tested because of their motor disability, bradyphrenia and speech impairment. There was also a tendency to attribute dementia in old age (and the great majority of PD patients are aged) to concurrent “senility” or “cerebral aterosclerosis” Once levodopa and dopa-agonist therapy was instituted this situation, surprisingly, did not change and the impression emerged that dementia is common in PD, more so in patients with advanced PD (Korczyn et al., 1986). Since then, overwhelming proof has accumulated that PD is accompanied by dementia in at least 20% of the cases. The debate over the issue of coincidental AD in demented PD patients is still not entirely resolved since some of the clinical and pathological features of the two dementias are similar.

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.