Richard G. Brown

Clinical diagnostic criteria for dementia associated with Parkinson's disease

Dementia has been increasingly more recognized to be a common feature in patients with Parkinsons disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD‐D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD‐D. The Task Force members were assigned to sub‐committees and performed a systematic review of the literature, based on pre‐defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD‐D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point‐prevelance is close to 30%, older age and akinetic‐rigid form are associated with higher risk. PD‐D is characterized by impairment in attention, memory, executive and visuo‐spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body‐type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD‐D are proposed.

THE ANATOMY OF MELANCHOLIA - FOCAL ABNORMALITIES OF CEREBRAL BLOOD-FLOW IN MAJOR DEPRESSION

Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.

Diagnostic Procedures for Parkinson's Disease Dementia : Recommendations from the Movement Disorder Society Task Force

A preceding article described the clinical features of Parkinsons disease dementia (PD‐D) and proposed clinical diagnostic criteria for “probable” and “possible” PD‐D. The main focus of this article is to operationalize the diagnosis of PD‐D and to propose pratical guidelines based on a two level process depending upon the clinical scenario and the expertise of the evaluator involved in the assessment. Level I is aimed primarily at the clinician with no particular expertise in neuropsychological methods, but who requires a simple, pragmatic set of tests that are not excessively time‐consuming. Level I can be used alone or in concert with Level II, which is more suitable when there is the need to specify the pattern and the severity on the dementia of PD‐D for clinical monitoring, research studies or pharmacological trials. Level II tests can also be proposed when the diagnosis of PD‐D remains uncertain or equivocal at the end of a Level I evaluation. Given the lack of evidence‐based standards for some tests when applied in this clinical context, we have tried to make practical and unambiguous recommendations, based upon the available literature and the collective experience of the Task Force. We accept, however, that further validation of certain tests and modifications in the recommended cut off values will be required through future studies.

International Multicenter Pilot Study of the First Comprehensive Self-Completed Nonmotor Symptoms Questionnaire for Parkinson's Disease: The NMSQuest Study

Nonmotor symptoms (NMS) of Parkinsons disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann–Whitney, Kruskal–Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.

Depression rating scales in Parkinson's disease: critique and recommendations.

Depression is a common comorbid condition in Parkinsons disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham‐D), Hospital Anxiety and Depression Scale (HADS), Zung Self‐Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery‐Asberg Depression Rating Scale (MADRS), Unified Parkinsons Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES‐D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer‐rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM‐D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES‐D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham‐D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time‐consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study

Non‐motor symptoms (NMS) in Parkinsons disease (PD) are common, significantly reduce quality of life and at present there is no validated clinical tool to assess the progress or potential response to treatment of NMS. A new 30‐item scale for the assessment of NMS in PD (NMSS) was developed. NMSS contains nine dimensions: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems, attention/memory, gastrointestinal, urinary, sexual function, and miscellany. The metric attributes of this instrument were analyzed. Data from 242 patients mean age 67.2 ± 11 years, duration of disease 6.4 ± 6 years, and 57.3% male across all stages of PD were collected from the centers in Europe, USA, and Japan. The mean NMSS score was 56.5 ± 40.7, (range: 0–243) and only one declared no NMS. The scale provided 99.2% complete data for the analysis with the total score being free of floor and ceiling effect. Satisfactory scaling assumptions (multitrait scaling success rate >95% for all domains except miscellany) and internal consistency were reported for most of the domains (mean α, 0.61). Factor analysis supported the a prori nine domain structure (63% of the variance) while a small test–retest study showed satisfactory reproducibility (ICC > 0.80) for all domains except cardiovascular (ICC = 0.45). In terms of validity, the scale showed modest association with indicators of motor symptom severity and disease progression but a high correlation with other measures of NMS (NMSQuest) and health‐related quality of life measure (PDQ‐8) (both, rS = 0.70). In conclusion, NMSS can be used to assess the frequency and severity of NMS in PD patients across all stages in conjunction with the recently validated non‐motor questionnaire.

Apathy in Parkinson’s disease

Objective: To assess apathy in patients with Parkinson’s disease and its relation to disability, mood, personality, and cognition. Methods: Levels of apathy in 45 patients with Parkinson’s disease were compared with a group of 17 similarly disabled patients with osteoarthritis. Additional neuropsychiatric data were collected concerning levels of depression, anxiety, and hedonic tone. Personality was assessed with the tridimensional personality questionnaire. Cognitive testing included the mini-mental state examination, the Cambridge examination of cognition in the elderly, and specific tests of executive functioning. Results: Patients with Parkinson’s disease had significantly higher levels of apathy than equally disabled osteoarthritic patients. Furthermore, within the Parkinson sample, levels of apathy appear to be unrelated to disease progression. The patients with Parkinson’s disease with the highest levels of apathy where not more likely to be depressed or anxious than those with the lowest levels of apathy, though they did show reduced hedonic tone. No differences in personality traits were detected in comparisons between patients with Parkinson’s disease and osteoarthritis, or between patients in the Parkinson group with high or low levels of apathy. As a group, the patients with Parkinson’s disease tended not to differ significantly from the osteoarthritic group in terms of cognitive skills. However, within the Parkinson’s disease sample, the high apathy patients performed significantly below the level of the low apathy patients. This was particularly evident on tests of executive functioning. Conclusions: Apathy in Parkinson’s disease is more likely to be a direct consequence of disease related physiological changes than a psychological reaction or adaptation to disability. Apathy in Parkinson’s disease can be distinguished from other psychiatric symptoms and personality features that are associated with the disease, and it is closely associated with cognitive impairment. These findings point to a possible role of cognitive mechanisms in the expression of apathy.

Depression in Parkinson's disease: a quantitative and qualitative analysis.

Depression is a common feature of Parkinsons disease, a fact of both clinical and theoretical significance. Assessment of depression in Parkinsons disease is complicated by overlapping symptomatology in the two conditions, making global assessments based on observer or self-ratings of doubtful validity. The present study aimed to provide both a quantitative and qualitative description of the nature of the depressive changes found in Parkinsons disease as compared with normal elderly subjects and arthritis patients. As with previous studies, the patients with Parkinsons disease scored significantly higher than normal controls on various self-ratings of depression and anxiety but, in this study, did not differ from those with arthritis. Qualitatively, both the Parkinsons disease and the arthritis groups had depression characterised by pessimism and hopelessness, decreased motivation and drive, and increased concern with health. In contrast, the negative affective feelings of guilt, self-blame and worthlessness were absent in both patient groups. This pattern of depression was significantly associated with severity of illness and functional disability. However, these factors account for only a modest proportion of the variability in test scores. Probable unexplored factors are individual differences in coping style and availability of support.

Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease

BACKGROUND Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimers disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. METHODS We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimers disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS. RESULTS Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone. CONCLUSIONS In patients with moderate or severe Alzheimers disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimers Society; Current Controlled Trials number, ISRCTN49545035.).

Prevalence of nonmotor symptoms in Parkinson's disease in an international setting: study using nonmotor symptoms questionnaire in 545 patients

2006, there was, no single instrument (questionnaire or scale) for attempting a comprehensive assessment of the wide range of nonmotor symptoms (NMS) of Parkinsons disease (PD). The PD nonmotor group, a multidisciplinary group of experts including patient group representatives developed and validated the NMS screening questionnaire (NMSQuest) comprising 30 items. The NMSQuest is a self completed screening tool designed to draw attention to the presence of NMS. In this paper, we present the results gathered from 545 patients using the definitive version of the NMSQuest highlighting the prevalence of the wide range of NMS flagged in the NMSQuest from consecutive PD patients in an international setting.