Ben Schmand

Diagnostic Criteria for Mild Cognitive Impairment in Parkinson’s Disease: Movement Disorder Society Task Force Guidelines

Mild cognitive impairment is common in nondemented Parkinsons disease (PD) patients and may be a harbinger of dementia. In view of its importance, the Movement Disorder Society commissioned a task force to delineate diagnostic criteria for mild cognitive impairment in PD. The proposed diagnostic criteria are based on a literature review and expert consensus. This article provides guidelines to characterize the clinical syndrome and methods for its diagnosis. The criteria will require validation, and possibly refinement, as additional research improves our understanding of the epidemiology, presentation, neurobiology, assessment, and long‐term course of this clinical syndrome. These diagnostic criteria will support future research efforts to identify at the earliest stage those PD patients at increased risk of progressive cognitive decline and dementia who may benefit from clinical interventions at a predementia stage.

Cognitive profile of patients with newly diagnosed Parkinson disease.

Objective: To determine the frequency and pattern of cognitive dysfunction in patients with newly diagnosed Parkinson disease (PD) and to identify its demographic and clinical correlates. Methods: A cohort of 115 consecutive patients with newly diagnosed PD and 70 healthy controls underwent a comprehensive neuropsychological assessment including tests of psychomotor speed, attention, language, memory, executive and visuospatial functions, as well as measures of affective status. Patients also received quantitative ratings of motor symptom severity and functional status. Neuropsychological performance of PD patients was compared with that of healthy controls and with available normative data. Independent demographic and clinical predictors of cognitive impairment were identified with multiple logistic regression analysis. Results: Relative to controls, PD patients performed significantly worse on most cognitive measures. However, further analysis revealed that group differences in cognitive performance could mainly be explained by measures of immediate memory and executive function. Comparison with normative data showed that impairments were most frequent on measures of executive function, memory and psychomotor speed. In all, 24% of PD patients (4% of controls) displayed defective performance on at least three neuropsychological tests and were classified as cognitively impaired. Late onset of disease was an independent predictor of cognitive dysfunction in PD. Conclusion: Cognitive impairments are common even in newly diagnosed Parkinson disease patients, with deficits being most prominent in the domains of memory and executive functions. Older age at disease onset is likely to be an important determinant of cognitive dysfunction in Parkinson disease.

Are memory complaints predictive for dementia A review of clinical and population-based studies.

Objectives. To review studies that have reported on the prevalence of memory complaints and the relationship between memory complaints and impairment or decline (dementia) in elderly individuals

Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson's disease (NSTAPS study): a randomised controlled trial

BACKGROUND Patients with advanced Parkinsons disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. METHODS We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinsons disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. FINDINGS Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinsons disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. INTERPRETATION Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinsons disease. FUNDING Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

Medial temporal lobe atrophy and memory dysfunction as predictors for dementia in subjects with mild cognitive impairment

Abstract To determine whether the medial temporal lobe is atrophic in subjects with mild cognitive impairment, and whether atrophy of this structure is a better predictor of dementia than memory dysfunction. Forty-five noninstitutionalized subjects aged 65–85 years were randomly selected from a population based study to obtain a sample with Alzheimer’s disease (AD; n = 7), and a clinically nondemented sample (n = 38). Twenty of the latter subjects displayed some cognitive impairment and fulfilled CAMDEX criteria for “minimal dementia.” Coronal T1-weighted magnetic resonance imaging was used to visualize the medial temporal lobe. The volume of the parahippocampal gyrus and hippocampus was measured, and medial temporal lobe atrophy was assessed qualitatively. The memory subscore from the CAMCOG was used as a measure of memory functioning. The follow-up period was 3 years. Nine subjects who were diagnosed as being minimally demented at baseline met the criteria for AD during follow-up. At baseline the volume of the parahippocampal gyrus of these subjects was smaller than that of the other subjects with minimal dementia. The memory score was the best predictor of clinical outcome. All medial temporal lobe measures increased the accuracy of prediction compared with only the memory score, by reducing the number of false-negative classifications of dementia. Severe medial temporal lobe atrophy is present even in some subjects with mild cognitive impairment and is an indicator of subsequent AD. The absence of medial temporal lobe atrophy, however, does not exclude the development of dementia. In the majority of subjects memory impairment was a better predictor of dementia than atrophy of the medial temporal lobe. The combination of the two increased predictive accuracy. Nondemented subjects with severe atrophy of the medial temporal lobe could be enrolled in drug trials aimed at slowing the progression of AD.

Subjective memory complaints may announce dementia

Article abstract-Whether subjective memory complaints in the absence of objective memory decline can predict future dementia has been investigated only in highly selected clinical and volunteer cohorts. Our study examines this question in a subsample of AMSTEL (Amsterdam Study of the Elderly), a longitudinal population study on cognitive decline and dementia. Subjects (aged 65 to 84 years; n = 357) without dementia or other psychiatric disorders at baseline were followed for 3 years. After this interval, 16 of 203 re-examined patients developed a dementia. Logistic regression analyses indicated that memory complaints at baseline contributed a small but significant amount of diagnostic information. However, the most powerful predictor of future dementia was deficient memory performance. We conclude that subjective memory complaints may predict dementia within 3 years, particularly when there are objective signs of memory deterioration. NEUROLOGY 1996;46: 121-125

Visual association test to detect early dementia of the Alzheimer type

Background: The visual association test (VAT) is a brief learning task based on imagery mnemonics. The test materials consist of six line drawings of pairs of interacting objects or animals—for example, an ape holding an umbrella. The person is asked to name each object and, later, is presented with one object from the pair and asked to name the other. Objective: To verify that the task induces robust incidental or effortless learning (study 1), and to study the efficiency of the test as a discriminator between early dementia of the Alzheimer type (DAT) and non-demented people (study 2) and non-DAT types of dementia (study 3). Methods: Study 1: two groups of elderly volunteers were administered the VAT. The stimuli were presented in the interactive fashion to group A—for example, a monkey carrying an umbrella (n=83)—and side by side to group B—for example, separate pictures of a monkey alone and an umbrella alone (n=79). Group B received learning instructions, but group A did not. Study 2: three groups of subjects were selected from a population based follow up study: incident DAT cases (n=24), cognitively declining subjects not diagnosed with dementia (n=21), and stable non-demented subjects (n=204). Test performance of the non-demented group at baseline was compared with that of patients with DAT at the time of their diagnosis, of patients with DAT a year before their diagnosis, and of non-demented declining subjects at baseline. Study 3: subjects were patients referred for neuropsychological assessment because of suspected dementia. They were diagnosed by consensus criteria of various dementia syndromes. Results: Study 1: recall was more than twice as high in group A as in group B. Thus interactive presentation, even in the absence of learning instructions, enhances learning. Study 2: at a level of 97.5% specificity, the VAT had a sensitivity of 87.5% for DAT cases at the time of diagnosis and 66.7% one year before diagnosis. The cognitively declining group scored significantly lower on the VAT at baseline than the non-demented group. The VAT discriminated more effectively than both the MMSE and the six item picture learning task from the CAMCOG. Study 3: VAT scores were significantly lower in patients with DAT (n=48) than in patients with vascular dementia (n=37), frontotemporal dementia (n=9), or subcortical dementia (n=15), but not lower than in patients with Lewy body dementia (n=7). Mean mini mental state examination scores of these groups were not significantly different. The VAT discriminated patients with DAT from patients with other types of dementia more effectively than a prose recall test. Sensitivity was 79% and specificity 69%. Conclusions: The VAT detects with high specificity a sizeable proportion of patients with DAT a year before the diagnosis, and a low VAT score is relatively uncommon in patients with non-DAT dementia.

Neuropsychological effects of bilateral STN stimulation in parkinson disease : A controlled study

Objective: To evaluate the cognitive and behavioral effects of bilateral subthalamic nucleus (STN) stimulation in patients with Parkinson disease (PD). Methods: The authors included 103 patients; 99 patients were evaluated 6 months after surgery. A control group of 39 patients with PD was formed and 36 patients were evaluated 6 months later. At baseline and at follow-up we administered neuropsychological tests of language, memory, visuospatial function, mental speed, and executive functions. A depression rating scale, a quality of life scale, self and proxy ratings of memory and dysexecutive symptoms, and a neuropsychiatric interview were also administered. Results: Six months after surgery, the STN group showed a larger decline than the control group on measures of verbal fluency, color naming, selective attention, and verbal memory. Moreover, the STN group showed a decrease in positive affect, and an increase in emotional lability and cognitive complaints. On the other hand, the STN group showed an increase in quality of life and a slight decrease in depressive symptoms. Nine percent of the STN patients had psychiatric complications (vs 3% of controls). Conclusions: Bilateral subthalamic nucleus stimulation has an adverse effect on executive functions with implications for daily life of the patients and their relatives.

Determinants of disability and quality of life in mild to moderate Parkinson disease

Objective: To identify factors that independently contribute to disability and quality of life (QoL) in patients with mild to moderate Parkinson disease (PD). Methods: A group of 190 patients with PD recruited from outpatient clinics and the Dutch Parkinson’s Disease Association participated in this cross-sectional study. Data on demographic and clinical factors, motor symptoms, cognitive functions, affective symptoms, comorbidity, and social support were collected during neurologic and neuropsychological examinations. Disability was rated using the Schwab and England Activities of Daily Living Scale (SE-ADL), the AMC Linear Disability Score (ALDS), and the Functional Independence Measure (FIM). QoL was assessed with the Parkinson’s Disease Quality of Life questionnaire (PDQL) and the Medical Outcome Study Short Form (SF-36). Multiple linear regression analyses were conducted to identify determinants of disability and poor QoL. Results: Axial impairment (postural instability and gait difficulty) explained the largest proportion of variance in disability. Bradykinesia and comorbidity contributed to disability, but to a lesser extent. Self-reported mood symptoms and axial impairment were the two factors most closely associated with poorer QoL, but comorbidity and bradykinesia additionally contributed to the explanatory power. Semantic fluency and psychomotor skills were the only cognitive variables related to some aspects of functional outcome. Conclusion: Axial impairment is strongly associated with disability in patients with mild to moderate Parkinson disease (PD). Self-report indices of mood status and axial impairment are identified as the main determinants of poor quality of life (QoL). The results of this study may help to identify patients with PD at risk for functional dependence and reduced QoL.

Memory disturbances in Ecstasy users are correlated with an altered brain serotonin neurotransmission

Abstract Rationale: Methylenedioxymethamphetamine (MDMA) is known to damage brain pre-synaptic serotonin (5-HT) neurons. Since loss of 5-HT neurons has been implicated in memory loss, it is important to establish whether MDMA use may produce changes in postsynaptic 5-HT receptors and memory function in humans. Objectives: To investigate whether MDMA use leads to compensative alterations in post-synaptic 5-HT2A receptors and whether there is a relation with memory disturbances. Methods: Brain cortical 5-HT2A receptor densities were studied with [123I]-5-I-R91150 SPECT in five abstinent MDMA users and nine healthy controls. Memory performance was assessed using RAVLT. Results: [123I]-5-I-R91150 binding ratios were significantly higher in the occipital cortex of MDMA users than in controls, indicating up-regulation. Mean cortical 5-HT2A receptor binding correlated positively with RAVLT-recall in MDMA users. Conclusion: Our preliminary results may indicate altered 5-HT neuronal function with correlated memory impairment in abstinent MDMA users.