Prevalence and clinical correlates of apathy in Parkinson's disease: a community-based study

The objective of this study was to examine the prevalence and clinical correlates of apathy in a population-based sample of patients with Parkinson's disease (PD) and to assess whether apathy may present as a primary behavioural disturbance independent from depression and cognitive impairment. A total of 232 patients derived from an epidemiological study of PD in Rogaland county, Western Norway, completed a comprehensive evaluation of motor, cognitive, and depressive symptoms. Apathy was assessed with the motivation/initiative item of the Unified Parkinson's Disease Rating Scale. The majority of the population had mild to moderate PD with mean disease duration of 9.1+/-5.7 years. Apathy was diagnosed in 38% of the 232 patients. In 11% of the total sample apathy coexisted with depression and dementia, whereas 10% had apathy and depression without dementia, 6.5% apathy and dementia without depression, and 9% were apathetic without dementia or depression (data missing in 1.5% patients). Apathy was significantly associated with higher depression scores, lower cognitive functioning, and more severe motor symptoms. When excluding patients with depression, dementia, cognitive impairment with no dementia (population-based age- and education-corrected norms for the Mini-Mental State Examination), and those using psychotropic medication, 5% of the 232 patients had apathy. In conclusion, our study shows that apathy is common in the general PD population, may present as an independent behavioural disorder, and suggests that apathy in PD may be related to dysfunction of the nigro-striatal pathway or that brain pathology underlying apathy and progression of motor symptoms develops in parallel.     

Clinical evaluation of Parkinson's disease dementia: association with aging and visual hallucination

OBJECTIVES: In order to explore factors associated with the development of dementia in Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), we systematically investigated the clinical evaluation of PD and DLB patients hospitalized in the Department of Neurology at Tottori University Hospital, Japan. RESULTS: There were 208 patients diagnosed as having PD and 39 patients diagnosed with DLB in this study. Of the patients with PD, 67 (32%) developed dementia and only five PD+ patients were considered to have cognitive impairment attributable to Alzheimer's disease (AD) or vascular dementia (VaD). Fifty-four (81%) PDD patients had visual hallucinations (VH) with or without cognitive fluctuation. The onset age of parkinsonian motor symptoms of patients with PD dementia (PDD) did not differ from that of PD patients without dementia. There was a significant inverse correlation between the onset age of motor symptoms in PD and the onset of their dementia in PDD. Seventy-five (36%) patients with PD had experienced VH and most of the PDD patients had experienced VH within 1 year before or after diagnosis of PDD. CONCLUSIONS: These results indicate that aging and VH are important factors associated with dementia in PD.     

An examination of executive dysfunction associated with frontostriatal circuitry in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson's disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function.     

Neuropsychological profile of patients with Parkinson's disease without dementia

Cognitive deficits are often associated with Parkinson's disease (PD), although their prevalence in PD patients without dementia is still unknown. In order to describe the neuropsychological profile of PD patients without dementia, a sample of 103 PD patients was compared with a control group consisting of 38 healthy elderly subjects. Psychometric assessment consisted of the Mini Mental State Examination, the Dementia Rating Scale and a battery of neuropsychological tests. The Beck Depression Inventory was used to assess depression in PD patients. Dementia was diagnosed in 27 patients. Among non-demented subjects, 34 (45%) had no cognitive impairment and 42 (55%) had a mild cognitive impairment. Subjects with mild cognitive impairment were older, had a later onset of the disease, and more severe motor symptoms than cognitively intact subjects. Identification of mild cognitive impairment is important, since these symptoms are important for patient management and may also facilitate to determine prognosis.     

Action fluency in Parkinson's disease: a follow-up study.

The impairment in action fluency task present in Parkinson's disease (PD) patients has been previously interpreted as an indicator of conversion from PD to PD with dementia or as a grammatical deficit for verbs and ascribed to a frontostriatal loop pathophysiology. In the present study, 20 patients with PD without dementia were longitudinally tested with overall cognitive decline scales and semantic, letter, and action fluency tasks in a 24-month follow-up study. In comparison with healthy age-matched controls, PD patients showed a stable and consistent impairment on action fluency without any sign of cognitive decline. Our findings suggest that action fluency task may be an early sign of impairment of frontostriatal circuits in PD and it cannot be considered an indicator of conversion from PD to PD with dementia.     

Cognitive and behavioural impairment in Parkinson's disease

Although Parkinson's disease (PD) has been considered to primarily affect motor abilities, increasing emphasis is being placed on cognitive and behavioural impairment in this disorder. Depression, dementia, psychosis and impulse control disorders have a major impact on quality of life for both patients and families. This article reviews cognitive and behavioural disturbances in PD and their relation to affective and motor symptoms, treatment of dementia associated with PD, and treatment approaches to psychosis in PD. We also discuss similarities between the dementia of PD and dementia with Lewy bodies.     

Autonomic and Cognitive dysfunction in Parkinson’s disease

Objective To investigate whether there is an association between autonomic failure and cognitive impairment in patients with idiopathic Parkinson’s disease (PD) Methods 40 PD patients and 30 age matched controls were assessed for cognitive and behavioral manifestations using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), the Blessed scale and Cornell scale for depression. The subjects were also assessed for orthostatic hypotension (OH), postprandial hypotension (PPH), heart rate responses to deep breathing (HR_DB) and autonomic symptoms using the Scale for Outcomes in PD for autonomic symptoms (SCOPA AUT). Results There was a correlation between the severity of motor symptoms and cognitive impairment in our PD patients. Eleven of the 40 PD patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria of dementia. The presence of OH or PPH did not correlate with the severity of cognitive impairment in our PD cases. However, PD patients with dementia reported more cardiovascular symptoms than PD patients without dementia. There was no correlation between gastrointestinal or urologic symptoms and cognitive impairment in our PD cases. Conclusion The results of this limited study indicate that despite the higher incidence of cardiovascular symptoms in PD patients with dementia than in those without dementia, there is no consistent association between OH or PPH and cognitive deficits in PD. The lack of correlation between OH, gastrointestinal and urinary symptoms with cognitive impairment suggests that cognitive and autonomic involvement progresses independently from each other and variably among PD patients.     

Differences in motor and cognitive function in patients with Parkinson's disease with and without orthostatic hypotension

Patients with Parkinson's disease (PD) often present with orthostatic hypotension (OH) as a result of the dysautonomia associated with the disease or as a side effect of the dopaminergic medications used to treat the disease. The purpose of this study was to investigate differences in motor and cognitive function in patients with PD with and without OH. Forty-four patients with a diagnosis of PD were evaluated and stratified by the presence of OH based on orthostatic blood pressure recordings. Both groups underwent assessments of motor and cognitive function. OH was present in 17 of 44 patients (39%) with PD. These patients with OH had significantly lower scores in gross motor, balance, and cognitive function (p < .05). No significant difference between groups was found in the finger tapping scores. These results suggest that patients with PD should be routinely screened for OH as it commonly occurs and may negatively impact gross motor, balance, and cognitive function.     

Neuropsychological follow up in patients with Parkinson's disease, striatonigral degeneration-type multisystem atrophy, and progressive supranuclear palsy

OBJECTIVES: Impairment of executive function is frequent in Parkinson's disease (PD), striatonigral degeneration-type multisystem atrophy (SND), and progressive supranuclear palsy (PSP); sometimes frank dementia is also present. However, the progression of cognitive decline has not been adequately studied. The objectives were to delineate the progression of cognitive impairment in these parkinsonisms and to elucidate interdisease differences. METHODS: Twenty three patients with SND and 21 with PSP, referred consecutively, and 18 patients with PD matched for severity of parkinsonism were compared on a comprehensive battery of cognitive tests and motor invalidity scales. A mean of 21 months later (range 18-24 months) the patients were called for retesting. RESULTS: Only 12 patients with PD (66.6%), 14 with SND (60.8%), and 11 with PSP (52.4%) were retested; those who dropped out refused, had died, or were too disabled. The patients with PSP performed worse than patients with PD or SND in the short tale, verbal fluency, visual search, and Benton tests at first evaluation. Overall cognitive performance was similar in the PD and SND groups except that the SND group did significantly worse on the verbal fluency test. Between group comparison of changes in scores from first to second evaluation showed that patients with PSP deteriorated significantly in the Nelson test compared with patients with PD or SND, and that patients with PSP or SND declined significantly on the visual search test compared with patients with PD. There was no difference between the groups for motor decline. Two patients with PSP were demented (DSM IV criteria) at first evaluation and six at second evaluation; no patients with PD or SND were demented at either evaluation. CONCLUSIONS: The greater decline of patients with PSP in attention, set shifting, and categorisation abilities is probably related to the conspicuous frontal deafferentation associated with direct premotor and prefrontal involvement, and to dysfunction of the midbrain ascending activating system, known to occur in PSP.     

Severity and specificity of cognitive impairment in Alzheimer's, Huntington's, and Parkinson's diseases and progressive supranuclear palsy

To investigate differences in severity and specificity of cognitive impairment among various neurodegenerative diseases, we tested groups of patients presenting with senile dementia of the Alzheimer type (SDAT; 44), progressive supranuclear palsy (PSP; 45), Huntington's disease (HD; 35) and Parkinson's disease (PD; 164), with an extensive neuropsychological battery. We found dementia, as defined by a global intellectual performance 2 standard deviations lower than mean control values, in 93% of SDAT, 66% of HD, 58% of PSP, and 18% of PD patients. Specific features of cognitive impairment distinguished the four groups of patients once they were matched for level of intellectual deterioration: remote memory and linguistic disorders in SDAT, frontal lobe-like abnormalities in PSP, concentration and acquisition disorders in HD. There was no specific alteration in demented PD patients. This study demonstrates the frequency of dementia in predominantly subcortical degenerative diseases and indicates that "subcortical dementia," rather than being a homogeneous entity, should be divided into specific subtypes of cognitive impairment related to different underlying specific lesions of each disease.     

Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease with dementia, and dementia with Lewy bodies

BACKGROUND: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson's disease patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with Parkinson's disease (PD). AIMS: (1) To examine rates of cognitive and motor decline over two years in PD (n=40), PDD (n=42) and DLB (n=41) subjects, compared with age matched controls (n=41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. RESULTS: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE -4.5 and -3.9, respectively), compared with PD (-0.2) and controls (-0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (chi2=6.7, Fisher's exact test p<0.05). CONCLUSION: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.     

The effect of depression on motor function and disease severity of Parkinson's disease

OBJECTIVES: Approximately 40% of patients with Parkinson's disease (PD) experience symptoms of depression. Our aim was to evaluate the effect of depression on disease severity, motor function and other phenotypic characteristics of PD. PATIENTS AND METHODS: We studied 32 PD patients with major depression (PD-D) according to the DSM-IV criteria and 32 PD patients with no depression (PD-C) matched for gender, age of onset and duration. RESULTS: Major depression in PD patients was associated with increased disease severity, poorer motor function and worse performance in the activities of daily living as measured by UPDRS scores. Furthermore, there was an association of depression with the severity of bradykinesia and axial rigidity. CONCLUSIONS: Depression in PD can have a profound negative impact on a patient's sense of wellbeing and motor functioning. Therefore, PD patients should be routinely and carefully screened for the presence of depression and appropriate management should be considered. Larger studies on the subject are warranted.     

Cognitive impairment patterns in Parkinson's disease with visual hallucinations.

OBJECTIVES: We investigated the role of stage of disease, motor status and dopaminergic treatment in cognitive impairment of Parkinson's disease (PD) patients with visual hallucination (VH) and the presence of specific cognitive impairment patterns. METHOD: We compared 33 PD patients with VH (group 1) with 30 PD patients without VH (group 2) with regard to demographic characteristics and neuropsychological test scores. RESULTS: The group with VH demonstrated significantly worse Short Test of Mental Status scores; the cognitive impairment pattern presented in the form of frontal dysfunction and memory deterioration. There were significant differences in Stroop duration/error, verbal fluency, Wechsler Memory Scale and Sozel Bellek Surecleri Test (a Turkish verbal learning test) scores. CONCLUSION: In PD patients with VH the main pattern of cognitive impairment is frontal dysfunction and memory deterioration. Because visual perceptive functions were not different between the two groups, such deterioration may not be a primary factor in the development of VH.     

Subthreshold depression in patients with Parkinson's disease and dementia--clinical and demographic correlates

BACKGROUND: About 40% of the patients with Parkinson's disease (PD) have depressive symptoms, either major depression (MD) or subthreshold depression. Depression was found to be associated with age and age at onset of PD, female gender, more severe parkinsonism, in particular with left-sided and akinetic-rigid symptoms, more functional impairment and cognitive impairment.However, the findings are inconsistent and partly contradictory and most of the studies focused on major depression in PD without dementia.The aim of this study was to examine the relationship between subthreshold depression and other clinical features in 538 PD patients with dementia but without MD drawn from a randomized, placebo-controlled multicentre trial of rivastigmine in PD. RESULTS: One hundred and sixteen patients (21%) had subthreshold depression. Depression was associated with a younger age and age at onset and female gender, but not with severity of parkinsonism, cognition or activities of daily living or laterality of motor symptoms. However, in male patients, an association between depression and left-sided parkinsonism was found. CONCLUSION: In contrast to previous findings in PD patients with major depression but without dementia, we found no relationship between subthreshold depression and other clinical symptoms in patients with PDD.     

Increases of pentraxin 3 plasma levels in patients with Parkinson's disease

Pentraxin 3 is a prototypic long pentraxin. Pentraxin 3 is a soluble recognition receptor that is involved in innate immunity and the inflammatory response. Its expression is induced by proinflammatory signals. The aim of this study was to compare the plasma levels of pentraxin 3 in healthy subjects and patients with neurodegenerative disorders such as mild cognitive impairment, Alzheimer's disease, and Parkinson's disease (PD). Thirty-nine patients with mild cognitive impairment, 75 patients with Alzheimer's disease, 66 patients with PD, and 41 healthy elderly controls were recruited for this study. We performed an extensive battery of neuropsychological tests, including a Mini-Mental Status Examination, clinical dementia rating, and the Unified Parkinson's Disease Rating Scale. A variety of clinical information was collected from the administered semistructured questionnaire. Plasma pentraxin 3 levels were measured using a specific enzyme-linked immunosorbent assay. Plasma pentraxin 3 levels were significantly higher in the PD patients than in the patients with mild cognitive impairment and Alzheimer's disease and in the control subjects. Plasma pentraxin 3 levels in the PD patients were correlated with activities of daily living (r = 0.368; P = .003) and motor function (r = 0.358; P = .004). Plasma pentraxin 3 levels could be a new biochemical marker for PD, and they may be associated with the severity of motor dysfunction and other clinical symptoms in PD patients.     

Neurocognitive Speed and Inconsistency in Parkinson's Disease with and without Incipient Dementia: An 18-Month Prospective Cohort Study

We examined two-wave longitudinal changes in two indicators of neurocognitive speed (i.e., mean rate, intraindividual variability) using one simple and three complex reaction time tasks. Participants included idiopathic Parkinson's disease (PD) patients, with and without incipient dementia, and normal controls. At baseline, there were 45 patients (26 men, 19 women) with idiopathic PD who ranged from 65 to 84 years (M = 71.3; SD = 4.5) and 47 matched controls (27 men, 20 women) who ranged from 65 to 84 years (M = 71.4; SD = 4.9). The 18-month longitudinal sample comprised of 74 returning participants (43 controls; 31 PD patients) who had no cognitive impairment or dementia at both waves. Ten of the 31 PD patients returning for Time 3 had dementia or cognitive impairment. These constituted the PD with incipient dementia (PDID) group. Repeated measures analyses of variance showed that the PD and PDID groups were slower over time on the reaction time tasks, whereas the controls improved their performance over time on all tasks. Inconsistency distinguished the two clinical groups (i.e., the PDID group but not the PD group became more inconsistent over time). Changes in neurocognitive speed and inconsistency may be valid clinical markers of PDID. (JINS, 2012, 18, 1-9).     

Cognitive impairment in nondemented Parkinson's disease

A substantial percentage of patients with newly diagnosed Parkinson's disease without dementia are reported to be affected by cognitive impairment (CI). In practice, however, CI is underrecognized, as the signs may not be apparent in early-stage disease and many routine assessment tools lack the sensitivity to detect subtle cognitive dysfunction. Patients with PD and mild CI (MCI) may have a higher risk of developing dementia than cognitively intact PD patients; however, it is not currently known which patients with CI are at increased risk of developing dementia. This review summarizes current knowledge about CI in nondemented PD; it discusses the structural and functional changes associated with CI and addresses areas of unmet needs. We focus on questions that should be addressed in future studies to achieve consensus on its characteristics and definition, pathophysiology, epidemiology, diagnosis and assessment, and treatment and management.     

Selective deficits in Alzheimer and parkinsonian dementia: visuospatial function

Deficits in visuospatial cognition are frequently cited as an important component of the cognitive changes accompanying Parkinson's disease. To characterize possible differences between Parkinson's (PD) and Alzheimer's (AD) dementia, patients from both groups, matched for overall dementia severity, age and education, were contrasted neuropsychologically. Visuospatial tasks dissociated from memory, were significantly compromised in both patient groups. Differential impairment was evident on visuospatial abstraction and reasoning (Object Assembly), which was most deficient in PD. Visuospatial cognition associated with memory, classified both patient groups as impaired compared to controls, but AD patients demonstrated substantially lower performance levels than those with PD. Parkinsonian dementia thus appears to have some distinct features compared to Alzheimer's disease, which may indicate differences in underlying pathogenic mechanisms.     

Controlled study of decision-making and cognitive impairment in Parkinson's disease.

Impulse control disorders (ICD) related to reward-processing dysfunction have been reported in Parkinson's disease (PD). The relationship between clinical markers of limbic dysfunction with demographic variables and cognitive status of PD is incompletely known. Our objective was to further characterize the relationship between limbic and cognitive dysfunction in a representative sample of nondemented PD patients without antecedents of ICD, as assessed by a risk-taking test of decision-making and a comprehensive neuropsychological battery. Prospective, controlled study of 35 nondemented PD patients and 31 matched controls who received the Iowa gambling task (IGT), the Mattis Dementia Rating Scale (MDRS) and verbal fluencies for global cognitive function, the Stroop and digit span tests for executive function, and the Rey Auditory Verbal Learning Test for memory. Compared to controls, PD patients performed significantly worse on the IGT. No clear relationship with demographic variables including dopaminergic treatment and motor response to levodopa (stable or fluctuating) emerged. Performance on the IGT was not related to executive function. In contrast, an inverse relationship was found between the IGT and memory and global cognitive performance, with patients with the better MDRS and memory scores performing significantly worse on the IGT. Our results confirm subclinical dysfunction of the limbic system in nondemented PD patients. Although impaired decision-making appears unrelated to executive dysfunction, patients with the better cognitive status appears more prone to assume risky behaviors.     

Dementia in Parkinson's Disease: Its Incidence and a Possible Relationship with Dopa-refractory Symptoms

Background : The diagnostic criteria for dementia in idiopathic Parkinson's disease (PD) remain controversial. In PD, general intelligence is relatively spared, although executive function is commonly impaired.
Methods : Following the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV), in this study we defined dementia in PD as a combined impairment of memory and executive function, and evaluated its incidence and its relationship with other clinical features.
Results : The prevalence of dementia among patients with PD was estimated to be 20–30% in an outpatient clinic and was found to be associated with the severity of motor impairments, especially Dopa-refractory symptoms. On the other hand, no relationships were observed between the prevalence of dementia and patient age or age of onset.
Conclusion : These data suggest that cognitive deficits, comprising dementia syndrome in PD, are mainly due to common neurodegenerative processes of non-dopaminergic systems, but not to other concomitant diseases, such as Alzheimer's disease.