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Background: Prescribed drugs in patients with Alzheimer's disease may affect the symptomatic progression of their disease, both positively and negatively., Aim: To examine the effects of drugs on the progression of disease in a representative group of patients with Alzheimer's disease., Methods: Patients with the diagnosis of probable Alzheimer's disease were recruited from the community. The prescribed drugs taken by 224 patients (mean age 82.3 years) were recorded at initial assessment and then correlated in logistic regression analysis with progression of the disease, defined as an increase of one point or more in the Global Deterioration Scale over the next 12-month period., Results: Patients who were taking antipsychotic drugs and sedatives had a significantly higher risk of deterioration than those who were taking none (odds ratios (ORs) 2.74 (95% confidence interval (CI) 1.17 to 6.41) and 2.77 (95% CI 1.14 to 6.73), respectively). Higher risk of deterioration was observed in those who were taking both antipsychotic and sedative drugs together (OR 3.86 (95% CI 1.28 to 11.7). Patients taking drugs licensed for dementia, drugs affecting the renin-angiotensin system and statins had a significantly lower risk of deterioration than those who were not taking any of these drugs (ORs 0.49 (95% CI 0.25 to 0.97), 0.31 (95% CI 0.11 to 0.85) and 0.12 (95% CI 0.03 to 0.52), respectively)., Conclusion: Our findings have implications for both clinicians and trialists. Most importantly, clinicians should carefully weigh any potential benefits of antipsychotics and benzodiazepines, especially in combination, against the risk of increased decline. Researchers need to be aware of the potential of not only licensed drugs for dementia but also drugs affecting the renin-angiotensin system and statins in reducing progression in clinical trials.

Objective: Most individuals with Parkinson's disease live in their own homes cared for by a family member. Providing such long term care can be a source of significant stress, with many carers experiencing sleep difficulty, depression, anxiety, loneliness, and other symptoms of psychological strain. Cognitive behavioural therapy (CBT) is one of the most widely used psychological treatments in clinical use today, with applications across the full range of clinical conditions. It has been previously used in the management of other carer groups. The present study sought to evaluate the efficacy of CBT in treating psychological distress in a group of Parkinson's disease carers., Method: A total of 30 carers scoring at caseness level on the 28 item General Health Questionnaire (GHQ-28) were randomised to receive either a course of 12-14 sessions of CBT or to a no-treatment control group., Results: Although some change was observed in both groups, significantly greater improvement on the GHQ-28 was observed after three months in the CBT treated group. Similar findings were observed in measures of caregiver strain and subjective burden, with the benefits being maintained over a subsequent three month follow up period., Conclusions: These results offer preliminary support to the value of a CBT approach in the management of psychological morbidity in Parkinson's disease carers. Further larger scale research is needed in the future to examine the generalisability of the findings to a broader range of carers, assess the longer term impact on outcome in carers and those with Parkinson's disease, and explore how CBT can be best delivered in the most cost effective manner.

Objectives: The authors report the results of detailed investigations into the motor function of a patient who, after a heavy drinking binge and subsequent unconsciousness, respiratory acidosis, and initial recovery, developed parkinsonism characterised by hypophonic speech and palilalia, "fast micrographia", impaired postural reflexes, and brady/akinesia in proximal (but not distal) alternating upper limb movements., Methods: In addition to brain magnetic resonance imaging (MRI), different aspects of motor function were investigated using reaction time (RT) tasks, pegboard and finger tapping tasks, flex and squeeze tasks, movement related cortical potentials (MRCPs), and contingent negative variation (CNV). Cognitive function was also assessed. The results were compared to those previously reported in patients with Parkinson's disease (PD)., Results: Brain MRI showed isolated and bilateral globus pallidus (GP) lesions covering mainly the external parts (GPe). These lesions were most probably secondary to respiratory acidosis, as other investigations failed to reveal an alternative cause. The results of the RT tasks showed that the patient had difficulties in preparing and maintaining preparation for a forthcoming movement. MRCP and CNV studies were in line with this, as the early component of the MRCP and CNV were absent prior to movement. The patient's performance on pegboard and finger tapping, and flex and squeeze tasks was normal when performed with one hand, but clearly deteriorated when using both hands simultaneously or sequentially., Conclusions: In general, the present results were similar to those reported previously in patients with PD. This provides further indirect evidence that the output of globus pallidus is of major importance in abnormal motor function in PD. The possible similarities of the functional status of GP in PD and our case are discussed.

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.

Background: Major depression is associated with cognitive deficits, particularly those requiring central executive functioning. Depressed patients also tend to focus on and think about their symptoms and problems ("ruminate") more than non-depressed controls. Although an association has been found between rumination and impaired performance on a central executive processing task, the causal relation between impaired executive functioning and rumination has not been determined. This study sought to directly manipulate rumination and assess the impact on executive functioning in depression as measured by random number generation., Methods: Depressed patients (n=14) and non-depressed controls (n=14) were compared on a random number generation task, performed after both a rumination induction and after a distraction induction, with order of inductions counter balanced within each group., Results: Compared with the distraction induction, the rumination induction produced a significant increase in both ruminations and the tendency towards stereotyped counting responses (thought to reflect a failure of inhibitory executive control) in depressed patients but not in controls. However, after distraction, no difference in random number generation or rumination was found between the two groups., Conclusions: The aspects of executive function involved in random number generation are not fundamentally impaired in depressed patients. In depressed patients, the rumination induction seems to trigger the continued generation of ruminative stimulus independent thoughts, which interferes with concurrent executive processing.

In both clinical and laboratory tests, patients with Parkinson's disease have considerable difficulty in performing different manual tasks simultaneously with the two hands. The present study reports on an unusual enhancement in performance under such conditions in a substantial proportion of patients tested. When performed at the same time as repetitive tapping tasks, the ability to rapidly place pegs in holes improved in almost half of the patients compared with unimanual performance of the peg task. Various possible explanations are considered for this unusual finding. The two most plausible, and testable, relate to either the withdrawal of attention from the task permitting a more automatic mode of execution, or a facilitation provided by sensory feedback from the simultaneous tapping task.

The aim of the study was to compare the quantitative and qualitative similarities and differences in the performance of patients with Parkinson's disease, Huntington's disease and cerebellar disease on a number of reaction time tasks. Simple reaction time (SRT), uncued and fully cued four choice (CRT) tasks were performed by eight patients with Parkinson's disease after withdrawal of dopaminergic medication for an average of 14.4 hours; by seven non-demented patients with Huntington's disease and by eight patients with cerebellar disease. An S1 (warning signal/precue)-S2 (imperative stimulus) paradigm was used in all tasks, with the S1-S2 interval randomly varying between 0, 200, 800, 1600 and 3200 ms across trials. The patients with Huntington's disease had a significantly longer SRT than those with Parkinson's disease. None of the other group differences in uncued and unwarned SRT and CRT was significant. For the patients with Parkinson's disease and those with cerebellar disease, unwarned SRT was faster than uncued and unwarned CRT. For the patients with Huntington's disease, this CRT/SRT difference was not significant. A warning signal before the imperative stimulus resulted in a reduction of reaction time in all three groups. Advance information provided by S1 about the response that would be required by S2 was used by patients in all three groups, evident from reaction times in the fully cued CRT task being faster than those in the uncued CRT condition. Patients with cerebellar disease had slower movement times in the SRT and CRT conditions compared with the patients with Parkinson's disease and Huntington's disease, whose times did not differ. In one SRT condition, when the absence of a warning signal was predictable, patients with cerebellar disease, and to a lesser extent those with Huntington's disease, were able to maintain a general motor readiness before the imperative stimulus. This was not the case for the patients with Parkinson's disease who seemed more dependent on the presence of a warning signal to reduce their reaction time. With a few exceptions, the pattern of results of the three groups were qualitatively similar. It may be concluded that similar reaction time deficits are found in Parkinson's disease, in patients with other disorders of the basal ganglia (Huntington's disease), as well as those with a disease sparing the basal ganglia (cerebellar disease). The non-specific slowness observed at the behavioural level may, however, have diverse central mechanisms.

Patients with Parkinson's disease have difficulty in performing two different tasks simultaneously. The present study tested whether this deficit was specific to the disease or was found in other patient groups. An identical pattern of performance was shown by a group of patients with cerebellar disease and, to a lesser extent, by a group of patients with Huntington's disease. Further research should focus on clarifying the nature of the deficits and the reasons for the similar performances in the various patient groups.

Eight patients with Parkinson's disease performed simple reaction time (SRT), uncued, partially and fully cued four choice (CRT) tasks. They were tested on two occasions; on their normal dose of dopaminergic medication and following withdrawal of such medication for an average of 14.4 hours. Disability as rated on the Webster scale was greater in the drug reduced state. Although RTs were generally slower when tested in the drug reduced state than when on medication, few differences emerged. Withdrawal of dopaminergic medication had no effect on unwarned SRT and unwarned and uncued CRT performance. Both on and off medication, the patients benefited from a warning signal presented before the imperative stimulus. In both medication states, the speeding up of RT was greatest with a warning signal presented 200 ms before S2. When the imperative stimulus was unwarned, the temporal predictability of its occurrence speeded RT more when on medication than when off. Advance movement parameter information was used by patients to pre-programme responses both on and off medication. In both medication states, the fully cued CRT was the same as SRT only with the 3200 ms S1-S2 interval. Medication state had no effect on movement time or the number of errors. It is suggested that slowness in motor readiness and motor programming may not be specific to striatal dopamine deficiency but rather a nonspecific concomitant of brain damage.

Depression with cognitive impairment, so called depressive pseudodementia, is commonly mistaken for a neurodegenerative dementia. Using positron emission tomography (PET) derived measures of regional cerebral blood flow (rCBF) a cohort of 33 patients with major depression was studied. Ten patients displayed significant and reversible cognitive impairment. The patterns of rCBF of these patients were compared with a cohort of equally depressed non-cognitively impaired depressed patients. In the depressed cognitively impaired patients a profile of rCBF abnormalities was identified consisting of decreases in the left anterior medial prefrontal cortex and increases in the cerebellar vermis. These changes were additional to those seen in depression alone and are distinct from those described in neurodegenerative dementia. The cognitive impairment seen in a proportion of depressed patients would seem to be associated with dysfunction of neural systems distinct from those implicated in depression alone or the neurodegenerative dementias.

Parkinson's disease leads to a breakdown in the execution of highly practised, skilled movements such as walking and handwriting. The improved execution of skilled movements with practice can be understood as a process of schema learning, the determining of the relevant parameters of the specific movement. The ability of patients with Parkinson's disease and age matched normal control subjects to improve their performance, with practice, on a skilled motor task, doing up buttons, was assessed. The task was assessed on its own and with simultaneous foot tapping. Both groups showed an initial improvement in the task on its own and deterioration in performance when buttoning with foot tapping. The amount of interference, however, decreased with practice, particularly in the patients with a 2 Hz tapping rate. The results suggest that patients with Parkinson's disease are capable of schema learning but require more practice than control subjects to achieve comparable levels of performance. This may be a reflection of the fundamental motor dysfunction of the disease rather than a specific learning deficit.

Sexual function in patients with Parkinson's disease has received virtually no attention. There are many reasons (physical, psychological and social), why such patients might experience problems within their sexual relationships. A group of patients and their partners completed a series of self-report measures, aimed at assessing sexual function and a range of factors which might be associated with any difficulties. The results revealed a high level of dysfunction, not just in the patients but also in their partners. Most effected were the couples in which the patient was male. A range of problems were reported by both patients and their partners. These were, in turn, associated with a range of variables relating to the disease, psychological and social factors. No simple causal model was suggested, and a multimodal therapeutic approach might be expected to have most benefit.

Sixteen patients with idiopathic Parkinson's disease were selected who were all showing severe fluctuations in motor function ("on-off" phenomenon). Measures of cognitive function and of subjective affect/arousal state were taken on two occasions, once when "on" and once when "off". Twenty-five matched normal controls were also assessed on the same measures. Results revealed, on the average, a drop in cognitive function plus an adverse swing in affect/arousal state, in the patient group in the "off" condition, compared to the levels when "on". Analysis of the data suggested that the main factor associated with cognitive function when "off" was not the severity of disability but the level of affect/arousal. The fluctuations in cognitive function found tended to be mild relative to the severe changes in motor ability, and were present in only a proportion of patients.

Depression is a common feature of Parkinson's disease, a fact of both clinical and theoretical significance. Assessment of depression in Parkinson's 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 Parkinson's disease as compared with normal elderly subjects and arthritis patients. As with previous studies, the patients with Parkinson's 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 Parkinson's 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.