Subjective memory complaints in elders: depression, anxiety, or cognitive decline?

OBJECTIVES: To study the association of subjective memory complaints (SMC) with affective state and cognitive performance in elders. MATERIALS AND METHODS: We studied community dwelling elderly persons with normal physical examination. Participants completed questionnaires regarding memory difficulties and lifestyle habits, the Geriatric Depression Scale (GDS) and the Spielberger State-Trait Anxiety Inventory (STAI). Depending on their answers to the question about their memory condition, participants were divided into complainers and non-complainers and to five groups according to their MMSE scores. These data have been compared to objective cognitive performance according to Mindstreams - a computerized neuropsychological battery. A logistic regression was performed to evaluate odds ratios (OR) and 95% confidence intervals (CI) for those factors, which were associated with SMС (dependent variable). RESULTS: Of 636 consecutive subjects (61% females), 507 participants (79.7%) had SMС. Presence of SMC was inversely correlated with MMSE scores, (r = -0.108; P for trend = 0.007). GDS and STAI scores were higher among subjects with SMC (OR = 1.23: CI 95%: 1.1-1.36 and OR = 1.03: CI 95%: 1.01-1.07, respectively). SMC did not correlate with objective cognitive performance measured by Mindstreams. CONCLUSIONS: Subjective memory complaints are associated with sub-syndromal depression and anxiety in healthy cognitively normal elders.

Subjective memory decline in healthy community-dwelling elders. What does this complain mean?

OBJECTIVES: Subjective feelings of memory decline are fairly common among the elderly. The causes of this are heterogeneous, and may be related to both affective and cognitive disorders. We attempted to explore the associations between subjective and cognitive measures. MATERIALS AND METHODS: Healthy subjects were studied. They completed questionnaires regarding memory difficulties and lifestyle habits, the Geriatric Depression scale (GDS), and the Spielberger State-Trait Anxiety Inventory. Cognitive functions were tested using the Mini-Mental State Exam and supplemented with NeuroTrax, a computerized neurophysiological battery. Univariate logistic regression model was applied to estimate odd ratios (OR) and 95% confidence intervals of associations. RESULTS: Of 341 consecutive non-depressed subjects, 257 participants (75.4%) reported subjective memory decline (SMD). Subjects with and without SMD did not differ in age, gender, education, marital status, employment and life-style. Subjects with SMD had elevated GDS scores (OR = 1.14, 95% CI: 1.003-1.29), white anxiety level showed a tendency to be increased (OR = 1.03, 95% CI: 0.99-1.06). Comparison of cognitive performance has not revealed differences in cognitive domains between subjects with and without SMD. CONCLUSIONS: SMD in healthy elderly people is associated with sub-clinical depression even among those without objectively measured cognitive decline.

Antiparkinsonian medication is not a risk factor for the development of hallucinations in Parkinson's disease.

BACKGROUND: It was commonly assumed that psychotic phenomena in Parkinson's disease (PD) are mainly drug related. Accumulating evidence suggests the existence of other risk factors for psychosis in PD. Aims. To evaluate the contribution of the drug profile of patients with PD to emergence of hallucinations. METHODS: We compared patients with and without hallucinations, using Cox proportional hazards model, concerning drug profile at the time of hallucinations emergence. RESULTS: Of 422 consecutive patients, 113 had dementia, while 90 patients experienced hallucinations (46 had both dementia and hallucinations). The mean levodopa dose for the group of patients with hallucinations was 650 +/- 279 mg/day at the time of hallucinations onset, which was not significantly different from the levodopa dose at last visit for the group without hallucinations (621 +/- 326 mg/day). Supplementary treatment with amantadine, selegiline, dopamine agonists, entacapone and anticholinergics did not increase the risk for the development of hallucinations. CONCLUSIONS: We did not confirm drug treatment as a risk factor for hallucinations in PD. Our study suggests the existence of "endogenic" factors as substantial contributors in the genesis of PD hallucinations. The clinical implications may be earlier administration of antipsychotic treatment and not as traditionally accepted, dose reduction of antiparkinsonian drugs.

Rivastigmine (Exelon) for dementia in patients with Parkinson's disease.

OBJECTIVES: To study the efficacy of cholinesterase inhibitors in the treatment of dementia in patients with Parkinson's disease (PD). METHODS: We treated twenty-eight demented patients with PD openly for 26 weeks with rivastigmine (mean daily dose 7.2 +/- 3.3 mg/day). Baseline scores were compared with those at weeks 12, 26 and after 8 weeks of washout. RESULTS: Twenty patients completed 26 weeks of treatment and eight dropped out because of side effects. The Unified Parkinson's Disease Rating Scale mental subscore improved significantly at week 26 (P < 0.01) while the motor score (part III) did not change. The mean ADAScog total score improved by 7.3 points at week 26 (P < 0.002). The subscores for recognition, word finding, remembering instructions and concentration items of the ADAScog improved significantly as well (P < 0.02, P < 0.05, P < 0.005 and P < 0.003, respectively). CONCLUSIONS: Rivastigmine may improve the cognitive functions in PD patients with dementia with no worsening of motor function.

Effects of rivastigmine on the quantitative EEG in demented Parkinsonian patients.

OBJECTIVES: Quantitative electroencephalogram (qEEG) can be used to measure the effects of drugs on the brain. We studied the effects of rivastigmine on the qEEG in Parkinson's disease (PD) patients with dementia. SUBJECTS AND METHODS: Demented PD patients (n=19) were treated with rivastigmine in an open label study. Recordings were obtained prior to and following 12 weeks of treatment. Results were analyzed using two-way ANOVA with repeated measures. RESULTS: A significant increase in the relative alpha (P < 0.05) activity was observed after treatment with rivastigmine. This was general rather than localized to specific brain surface areas. An increase in beta activity and decrease in the slower frequencies (delta and theta) were also observed; however, these were not statistically significant. CONCLUSION: qEEG may serve as an objective tool to monitor the effects of antidementia drug therapy. The changes characterized by increased faster frequencies and decreased slower frequencies that were observed may indicate increased arousal or improvement in the cognitive state of the patients as a consequence of the treatment with rivastigmine.

Quality of sexual life in Parkinson's disease.

Ninety-one consecutive patients with Parkinson's disease (PD) were asked to grade their general satisfaction from life (GSL) and completed the PDQ-39 and the quality of sexual life questionnaire (QoSL-Q). The reliability of the QoSL-Q was 0.74. Satisfaction from sexual life as reflected by the QoSL-Q significantly decreased with aging (P<0.01) and advanced disease (P<0.05). No correlation was found between the PDQ-39 and the QoSL index. The correlation between the PDQ-39 and GSL (r=-0.334) improved by adding the QoSL-Q, as a 9th dimension to the PDQ-39 (r=-0.405). The QoSL-Q is a reliable tool assessed a unique and important dimension not evaluated by the PDQ-39.

Cross-sectional study of the prevalence of Parkinson's disease in the Kibbutz movement in Israel.

BACKGROUND: The prevalence of PD in Israel has never been studied. OBJECTIVE: To study the prevalence of Parkinson's disease (PD) in a well-defined population of the Kibbutz Movement in Israel. The population which lives in kibbutzim is unique because all these people are under close medical care and the demographic data regarding this population are well defined. METHODS: Questionnaires were sent to the medical clinics of 270 kibbutzim in Israel to provide demographic details as well as medical information about all PD patients who have been diagnosed by neurologists. Two subgroups were determined: aged over 40 years and over 60 years. RESULTS: Of the total of 73,767 people studied, PD was diagnosed in 180 patients yielding a cross-sectional prevalence rate of 0.24% for the entire population. Age-adjusted prevalence was 0.94% in the population over 60 years and 0.33% in the population over 40 years. The mean age of disease onset was 66.7 +/- 11 years. Topographic location was not found to be a risk factor for the development of PD in Israel. CONCLUSIONS: The prevalence of PD in the Israeli kibbutz population is similar to that reported in most other population-based studies. We observed an older age at symptom onset in the Kibbutz Movement than most other epidemiological studies.

The effect of botulinum toxin injections to the calf muscles on freezing of gait in parkinsonism: a pilot study.

BACKGROUND: Freezing of gait (FOG) is a common and very disabling parkinsonian symptom, which is poorly understood and responds unsatisfactorily to medical treatment. We recently reported a unique patient with Parkinson's disease (PD) who had significant alleviation of FOG shortly after she was injected with botulinum toxin type A (BTX-A) for foot dystonia (Giladi et al. 1997). OBJECTIVE: To assess the effect of BTX-A injections into the calf muscles of parkinsonian patients on FOG. METHOD: BTX-A was injected in an open fashion into the calf muscles of 10 parkinsonian patients (age 55-75 years) with FOG as a predominant symptom. Response of FOG was assessed subjectively by the patient from worsening (-1) to marked improvement (+3). One patient was injected in a single blind fashion with saline or BTX-A after he had an initial good response. RESULTS: Seven patients reported different rates of improvement of FOG severity in 15 out of 17 therapeutic sessions. Four patients (40%) reported marked improvement (+3) of FOG in 5 sessions. Two patients reported no effect in two sessions. The mean duration of improvement was 6 weeks (range 1-12 weeks) with definite deterioration afterwards. The patient who was injected in a single blind fashion did not respond to saline injections but improved significantly with BTX-A treatment. CONCLUSIONS: We observed a clear temporal relationship between BTX-A injections into the calf muscles of parkinsonian patients and improvement of FOG. A double blind placebo controlled prospective study is needed before any conclusions can be drawn about the role of BTX-A injection in FOG.

Freezing of gait in patients with advanced Parkinson's disease.

BACKGROUND: Freezing of Gait (FOG) is one of the most disturbing and least understood symptom in advanced stage of Parkinson's disease (PD). The contribution of the underlying pathological process and the antiparkinsonian treatment to the development of FOG are controversial. OBJECTIVE: To study the relationships between clinical features of PD and therapeutic modalities in patients with advanced PD and FOG. METHODS: Consecutive patients with 5 years or more of PD symptoms (n = 172) (99 men) with mean age at symptoms onset of 58.3 +/- 13.2 years and mean symptoms 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 patients' charts, and other documents. A patient was considered as "freezer" if he/she reported recent experience that the legs got stuck to the ground while trying to walk. The presence of dyskinesia, early morning dystonia or significant postural reflex abnormalities were assessed through history and neurological examination. Duration of treatment with antiparkinsonian drugs was calculated from history charts. Chi square and t test were used to compare the patients with and without FOG. Logistic regression was used for the comparison of association between the presence of FOG (dependent variable) disease duration and disease stage (explanatory variables) and duration of treatment with anti-parkinsonian drugs. RESULTS: The study population consisted of 45 patients at Hoehn and Yahr (H&Y) stage 2.5 (26%), 104 patients at stage 3 (60.5%), and 23 patients at H&Y stages 4-5 (13.5%). Ninety one patients (53%) reported FOG at the time of the study. Severity of the disease expressed by H&Y stage at "off" was a significant contributing factor for FOG with a significant trend (z = 4.38, p < 0.0001), as was longer duration of levodopa treatment, and confirmed by FOG using the multivariate logistic regression (p = 0.01 and p = 0.004, respectively). Using a univariate model, longer duration of treatment with dopamine agonists contribute to the appearance of FOG (p = 0.07) while longer duration of amantadine treatment decreased the appearance of FOG (p = 0.09). There was a significant association between FOG and the presence of dyskinesia (p < 0.002), early morning foot dystonia (p < 0.003) and significant postural instability (p < 0.0005). CONCLUSION: FOG is a common symptom in advanced PD. It is mainly related to disease progression and levodopa treatment.

Gait festination in Parkinson's disease.

Background: Festinating gait (FSG) was first associated with parkinsonism by Sir James Parkinson, in his original essay on "The Shaking Palsy". Its frequency and relation to other parkinsonian features have never been assessed.Objective: To study the relationships between gait festination and other parkinsonian clinical features among patients with Parkinson's disease (PD).Method: During an open lecture to patients with PD who are followed at the Movement Disorders Unit (MDU) of Tel-Aviv Sourasky Medical Center one of us explained verbally and imitated festinating gait on stage. All attending patients with the help of their care-givers or family members, were asked to answer two written questions regarding their own experience with FSG as well as the degree of disability it causes. Clinical information about each patient was taken from his/her chart at the MDU and missing data was completed during the next office visit or from the family physician. Statistical analysis was performed using t-tests for comparison between groups, Chochran-Armitage test for trends and logistic regression to assess the contribution of age of onset, disease duration and disease severity to the development of FSG.Results: Eighty-one PD patients (58 males, mean age 67.5+/-10.7years) answered the FSG questionnaire. Our study population's mean disease duration was 8.5+/-6.4years, mean Hoehn and Yahr (H&Y) clinical stage of 2.6+/-0.8 and mean levodopa dose of 608+/-375mg/day (15 patients were not on levodopa). Twenty-six patients (32.1%) experienced FSG during the previous month and 56% of them reported that FSG was a significant and disabling symptom. FSG was strongly associated with higher stage of H&Y (p<0.001) with a significant trend as the disease progresses (p=0.001) but not with total score in the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). Longer disease duration was the only clinical factor, which was found to be associated with FSG in the multivariate model. Thirty seven percent (37%) of the patients with FSG reported frequent falls with association between occasional or frequent falls, as reported on the activity of daily living (ADL) part of the UPDRS, and the presence of FSG (p<0.08). There was no association between significant postural reflex abnormalities as rated on the objective part of the UPDRS and the presence of FSG. There was a significant association between the presence of freezing of gait (FOG) as reported in the ADL part of the UPDRS and the presence of FSG (p<0.001) as well as a significant trend towards more frequent FSG in patients with more severe FOG (p<0.001).Conclusion: FSG was clearly associated with longer duration of PD symptoms but not with disease severity as reflected in the motor part of the UPDRS. The relationships between FSG and postural reflexes abnormalities is unclear but it is frequently associated with falls and freezing of gait.

Clinical characteristics of neuroleptic-induced parkinsonism.

In order to characterize the clinical spectrum of neuroleptic-induced parkinsonism (NIP), we studied a population of consecutive psychiatric in-patients treated with neuroleptics for at least two weeks, who were diagnosed by their psychiatrist as having parkinsonism. Parkinsonism was confirmed by a movement disorders specialist who performed neurological assessment including the motor examination and the activities of daily living (ADL) sections of the Unified Parkinson's Disease Rating Scale (UPDRS), and the Hoehn and Yahr (H&Y) staging. Seventy-five patients (54 males), aged 46 +/- 13 years (range 21 to 73 years) were included in the analysis. The mean duration of neuroleptic therapy was 15 +/- 12 years, while 61% were treated for more than 10 years. Most of the patients (n = 66, 88%) were scored as H&Y stage 2.5 or less. Rest tremor was present in 44% of the patients, and usually persisted in action. Forty-one patients (61%) had symmetrical involvement. Parkinsonian signs were significantly more common and pronounced in the upper in comparison with the lower limbs (p = 0.0001). Gait disturbances were mild and freezing of gait was very rare (n = 2). Neither age nor duration of therapy or their interaction affected the total motor score or any of the motor sub-scores. In conclusion, NIP differs from PD for more bilateral involvement with relative symmetry, and by affecting upper limbs more often than the lower ones. NIP tends to be associated with the triad of bradykinesia, tremor and rigidity while PD tends to involve gait and posture more often. NIP develops unrelated to duration of neuroleptic treatment or age of the patient, suggesting an individual predisposition to blockage of the dopaminergic receptors.

Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson's disease.

Clinical distinction of multiple system atrophy (MSA) from Parkinson's disease (PD) is often difficult. Several recent reports indicate that objective classification may be accomplished using electromyographic (EMG) testing of the anal or urethral sphincters, but some authors have found that these tests are not reliable for this purpose. We studied 13 patients with PD and 10 with probable MSA, as diagnosed by consensus of four movement disorders specialists, according to accepted clinical criteria. Anal sphincter EMG was performed blind to the clinical diagnosis. We found no significant differences in the mean duration of motor unit potentials (MUPs), mean MUP amplitude, or prevalence of polyphasic potentials, satellite potentials, very long duration MUPs, or spontaneous activity between the two groups. Thus, anal sphincter EMG does not differentiate between PD and MSA.

Construction of freezing of gait questionnaire for patients with Parkinsonism.

Background: Freezing of gait (FOG) is a common, poorly understood, parkinsonian symptom interfering with daily functioning and quality of life. Assessment of FOG is complex because of the episodic nature of this symptom, and the influence of mental and environmental factors on it.Objective: To design a self-reportable reliable questionnaire for FOG.Method: A questionnaire consisting of 16 items regarding gait and falls was administered together with the Unified Parkinson's Disease Rating Scale (UPDRS) to 40 Parkinson's disease (PD) patients (26 males) with a mean age of 72.3+/-9.3 years and mean Hoehn and Yahr (H&Y) stage at "Off" of 2.85+/-0.84. A principal component analysis with Varimax rotation was conducted on the results. Item analyses were performed and reliability computed for an abbreviated FOG questionnaire.Results: Based on these analyses, a short (six item) FOG questionnaire was constructed, which was found to be highly reliable (Cronbach alpha=0.94) for assessment of FOG and with moderate correlation with the activity of daily living (ADL) and motor parts of the UPDRS (0.43 and 0.40, respectively). Moderate correlation was also found with the FOG item at the ADL part of the UPDRS (alpha=0.66 for the "Off" and 0.77 for the "On" state).Conclusion: The FOG questionnaire that was constructed is highly reliable in assessing freezing of gait, unrelated to falls, in patients with PD.

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

OBJECTIVES: To study the relationships between clinical features of Parkinson's 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 < or = 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 (> or = 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 (beta = 0.04, p = 0.009) while depression was inversely associated with age of PD onset (beta = -0.04, p = 0.02). The presence of dementia was also significantly associated with depression (beta = 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.

Germline mutational analysis of presenilin 1 and APP genes in Jewish-Israeli individuals with familial or early-onset Alzheimer disease using denaturing gradient gel electrophoresis (DGGE).

Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2). The relative proportions in which mutations in these genes occur among AD patients in Israel has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with AD: 22 with sporadic, early-onset disease (below 65 years), and 30 with FAD. Mutation screen employed denaturing gradient gel electrophoresis (DGGE) of exon-specific PCRs and restriction enzyme digest. Five patients from three different families displayed mutations within the PS-1 gene: three patients of one family showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated patients showed an identical mis-sense mutation in codon 318 (Glu318Gly). No patient showed an abnormal migration on DGGE (for APP) or mutant restriction digest pattern (for PS-2) genes. These data may indicate the existence of another familial Alzheimer disease (FAD) gene locus in the Israeli Jewish population.

Pruritus in Creutzfeldt-Jakob disease.

We report three patients with Creutzfeldt-Jakob disease, whose first symptom was severe pruritus, similar to that observed in scrapie. The pruritus was resistant to therapy. The underlying mechanisms are unclear, but we speculate that the pruritus may result from brainstem involvement.

Post-traumatic stress disorder in myocardial infarction patients: prevalence study.

This study examined the prevalence of post-traumatic stress disorder (PTSD) in a sample of 100 Israeli myocardial infarction (MI) patients. Chronic PTSD was diagnosed in 16% of these patients and acute (PTSD) in 9%. The appearance of PTSD following MI was found to be related to the following variables: ethnic background; prior traumatic experiences, including prior MI; and anticipation of disability following MI. Objective measures of MI severity were not related to propensity to develop PTSD. The presence of PTSD correlated with self reports of dysfunction in these MI patients and may account for the majority of failures in rehabilitation.