Visual recognition memory differentiates dementia with Lewy bodies and Parkinson's disease dementia

Objective

To compare cognitive impairments in dementia with Lewy bodies (DLB) and Parkinson''s disease dementia (PDD), to discriminate between the two entities.

Methods

10 DLB and 12 PDD consecutive patients performed a neuropsychological battery designed to assess several cognitive domains: verbal and visual memory (Delayed Matching to Sample (DMS)‐48), language, gnosia, praxia and executive functions.

Results

DLB patients had poorer performances in orientation (p<0.05), Trail Making Test A (p<0.05) and reading of names of colours in the Stroop Test (p<0.05). Their scores were also lower in the visual object recognition memory test (DMS‐48), in both immediate (p<0.05) and delayed recognition (p<0.05). No differences were observed in the other tests.

Conclusion

Despite global similarities in cognitive performances between DLB and PDD patients, we observed important differences: in particular, DMS‐48, a test of visual object recognition memory and visual storage capacity, was poorer in DLB patients.Parkinson''s disease dementia (PDD) and dementia with Lewy bodies (DLB) share some common clinical features, such as extrapyramidal symptoms and neuropsychological impairment.^1,2,3 In practice, consensus guidelines recommend an arbitrary distinction between the two disorders based on a temporal sequence of 1 year between the presentation of extrapyramidal motor symptoms and the manifestation of dementia: PDD is diagnosed if dementia occurs belatedly in the context of well established Parkinson''s disease; DLB is diagnosed when motor and cognitive signs appear during the first year of evolution.⁴ A key question is whether this is a meaningful distinction between the two different clinical entities.Subtle clinical distinction in terms of cognitive pattern could prove useful for clinicians.In this study, we compared cognitive performances in a group of patients with a clinical diagnosis of “probable” DLB with those of PDD patients. As the clinical symptoms overlap, our aim was to determine possible differences in the cognitive abilities between DLB and PDD.     

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.     

Ventricular dilatation and brain atrophy in patients with Parkinson's disease with incipient dementia

Age‐related ventricular enlargement is accelerated in Alzheimer's disease, but its relationship to cognitive decline in Parkinson's disease is less clear, even though dementia is common in Parkinson's disease. Our goals were to determine if greater enlargement of the ventricles and gray or white matter atrophy occurred in Parkinson's disease patients developing cognitive decline. Older nondemented patients with Parkinson's disease (33) and age‐ and sex‐matched controls (39) were recruited and prospectively assessed for the development of significant cognitive decline over 36 months. Magnetic resonance imaging was obtained every 18 months, and ventricular volume and total brain gray and white matter volumes were measured using reliable segmentation of T1‐weighted volumetric scans. Subjects with incidental intracranial abnormalities, an atypical course, and stroke as well as dropouts were excluded from a cohort of 52 patients and 50 controls. Among 33 patients and 39 controls, 10 patients and 3 controls developed significant cognitive impairment or dementia. Ventricular change and Parkinson's disease status were significantly associated with dementia. Ventricular change was significantly correlated with change in Mini‐Mental Status Examination in the Parkinson's disease with dementia group (r = 0.87, P = .001). Gray matter atrophy was greater in Parkinson's disease with dementia, with similar change over time in both Parkinson's disease and Parkinson's disease with dementia. White matter volumes were not significantly different between Parkinson's disease and Parkinson's disease with dementia; however, the decrease over time might be greater in Parkinson's disease with dementia. Ventricular dilatation occurs early in the course of significant cognitive decline in patients with Parkinson's disease, possibly reflecting both cortical gray and white matter loss. © 2011 Movement Disorder Society     

Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes

OBJECTIVE: To determine whether MRI volumetric measurement of the entorhinal cortex could detect structural damage and lateralize the seizure focus in patients with temporal lobe epilepsy in whom no measurable hippocampal abnormalities were found. BACKGROUND: A reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy and hippocampal atrophy was recently shown. METHODS: MRI volumetric analysis of the entorhinal cortex was performed using a T1-weighted three-dimensional gradient echo sequence in 24 control subjects and 22 patients with temporal lobe epilepsy and normal hippocampal volumes. Thirteen patients underwent surgery, with a mean postoperative follow-up of 36 months. RESULTS: Group analysis (multivariate analysis of variance) showed a reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with left (p < 0.0001) and right temporal lobe epilepsy (p < 0.0001). Lateralization of the seizure focus could be done in 14 of 22 patients (64%) based on entorhinal cortex volumetry. CONCLUSION: Entorhinal cortex atrophy ipsilateral to the seizure focus supports the presence of structural damage in the mesial temporal lobe in patients with temporal lobe epilepsy and normal hippocampal volumes and emphasizes the participation of the entorhinal cortex in the pathogenesis of this disorder.     

Brain atrophy rates in Parkinson's disease with and without dementia using serial magnetic resonance imaging.

Increased rates of brain atrophy are seen in Alzheimer's disease, but whether rates are similarly increased in other dementias such as Parkinson's disease dementia (PDD) has not been well examined. We determined the rates of brain atrophy using serial magnetic resonance imaging (MRI) in PDD and compared this finding to rates seen in cognitively intact Parkinson's disease (PD) patients and age-matched control subjects. Thirty-one patients (PD = 18, PDD = 13) and 24 age-matched controls underwent serial volumetric 1.5 T MRI scans, approximately 1 year apart. Baseline and repeat scans were registered and quantification of the brain boundary shift integral was used to determine whole-brain atrophy rates. Rates of brain atrophy were significantly increased in PDD (1.12 +/- 0.98%/year) compared to PD (0.31 +/- 0.69%/year; P = 0.018) and control subjects (0.34 +/- 0.76%/year; P = 0.015). There were no differences in atrophy rates between controls and PD (P = 0.79). No correlations between increased atrophy rates and age or dementia severity (Mini-Mental State Examination score) were observed. Serial MRI may be a useful tool for monitoring disease progression in PDD and further studies should investigate its utility for early diagnosis.     

Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia

OBJECTIVE: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. METHODS: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AD among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. RESULTS: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. CONCLUSIONS: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.     

Cerebrospinal fluid analysis differentiates multiple system atrophy from Parkinson's disease.

We investigated whether cerebrospinal fluid (CSF) analysis discriminates between idiopathic Parkinson's disease (PD; n = 35) and multiple system atrophy (MSA; n = 30). The median CSF concentration of the neurotransmitter metabolites 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) was reduced significantly (49-70%) in MSA compared to PD. In contrast, several brain-specific proteins (tau, neuron-specific enolase, myelin basic protein) were elevated (130-230%) in MSA compared with those in PD. A combination of CSF tau and MHPG discriminated PD from MSA (adjusted odds ratios: tau, 27.2; MHPG, 0.14). Our data suggest that the more progressive and widespread neurodegenerative nature of MSA, as compared with PD, is reflected in the composition of CSF. We propose that CSF analysis may become part of the diagnostic work-up of patients with parkinsonian syndromes.     

Release signs in Parkinson's disease with and without dementia

Summary Release signs have been described in both age-associated diseases and in the healthy elderly. We investigated the palmomental, snout, grasp, corneomandibular and glabellar reflexes in demented and non-demented Parkinson-patients compared to Alzheimer's disease and age-matched controls. The palmomental reflex and a persisting glabellar reflex were linked to parkinsonism irrespective of dementia and were found also in Alzheimer's disease. A corneomandibular reflex was observed more frequently in demented than non-demented Parkinson-patients and in Alzheimer's disease. The snout-reflex was present in nearly all individuals irrespective of diagnosis. Thus, various release signs react quite differentially to degenerative brain disease and dementia.     

T2*-weighted MRI differentiates multiple system atrophy from Parkinson's disease

To compare the ability of T2*-weighted gradient echo (GE) and T2-weighted fast spin echo images to distinguish between patients with idiopathic PD and multiple system atrophy (MSA), the authors studied 15 patients with probable MSA, 40 patients with PD, and 17 healthy control subjects. Hypointense putaminal signal changes were more often observed in MSA than in PD using T2* but not T2-weighted images, indicating that T2*-weighted GE sequences are of diagnostic value for patients with parkinsonism.     

Apolipoprotein E genotypes in Parkinson's disease with and without dementia

The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset of Alzheimer's disease. Because Parkinson's disease shares many characteristics of Alzheimer's disease, we studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease patients with dementia and 61 patients without dementia. Dementia was determined per National Institute of Neurological and Communicative Disorders and Stroke criteria and Mattis Dementia Rating Scale (DRS) < 126. Normal cognition was defined as DRS > 132. Apo E genotype and allele frequencies did not differ between demented and nondemented parkinsonian patients. Neither group's genotype and allele frequencies differed from that of a nondemented population of 78 controls. We conclude that the Apo E ε4 allele influences neither the development of Parkinson's disease nor the dementia associated with Parkinson's disease nor the dementia associated with Parkinson's disease.     

Quantified electroencephalographic changes in Parkinson's disease with and without dementia

We examined the presence of quantified electroencephalographic (qEEG) differences between Parkinson's disease (PD) patients with and without dementia, and a group of age-comparable normal controls. While there were no significant differences in relative power in any of the qEEG bands between PD patients without dementia and normal controls, PD patients showed a significantly greater reactivity in the alpha band. On the other hand, PD patients with dementia showed significantly less alpha and more theta relative power than both the normal control and the PD without dementia groups. When PD patients with dementia were compared with a group of patients with Alzheimer's disease (AD) and a similar severity of dementia, no significant between-group differences were found in any of the qEEG bands. In conclusion, while our study demonstrated no significant qEEG differences between non-demented PD patients and normal controls, PD patients with dementia showed qEEG changes similar to those observed in patients with AD.     

Cognitive impairment in Parkinson's disease without dementia

Some degree of cognitive impairment appears frequently in Parkinson's disease (PD) patients, even at the onset of the disease. However, due to the heterogeneity of the patients and the lack of standardized assessment batteries, it remains unclear which capacities are primarily affected by this disease. Fifty PD patients were assessed with 15 tests including executive functions, attention, temporal and spatial orientation, memory, and language tasks. Their results were compared with those of 42 age‐ and education‐matched healthy seniors. Semantic fluency, along with visual search appeared to be the most discriminant tasks, followed by temporal orientation and face naming, as well as action naming and immediate recall. PD patients studied showed an impairment of frontal‐ to posterior‐dependent capacities. Executive functions, attention, and recall tasks appeared to be significantly impaired in the patients. Nevertheless, significantly poor scores in tasks like action and face naming, as well as semantic fluency, also reveal a mainly semantic deficit. © 2010 Movement Disorder Society     

Cerebral glucose metabolism in Parkinson's disease with and without dementia.

Although cognitive impairment is commonly associated with Parkinson's disease, the relative importance of cortical and subcortical pathologic changes to the development of dementia is controversial. Characteristic abnormalities in cortical glucose metabolism have been reported previously in Alzheimer's disease, a disease in which cortical changes predominate. We measured cerebral glucose metabolism with positron emission tomography in 20 control subjects and in 14 patients with PD with mental status ranging from normal to severely demented to determine whether changes in cortical glucose metabolism occur in early PD and whether the degree and pattern of metabolic change relate to the severity of dementia. The patients were divided into demented and nondemented groups according to the results of neuropsychological assessment. Age-adjusted covariance analyses were performed, since the age distribution varied between groups. The nondemented patients with PD showed widespread cortical glucose hypometabolism without any selective temporoparietal defects. The pattern of glucose hypometabolism seen in the demented patients with PD resembled that described in patients with Alzheimer's disease; ie, there was a global decrease in glucose metabolism, with more severe abnormalities observed in the temporoparietal regions.     

Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are alpha-synucleinopathies

Parkinson's disease is neuropathologically defined by the presence of intracytoplasmic Lewy bodies and Lewy neurites. Similar filamentous inclusions are also present in dementia with Lewy bodies, a common late-life dementia, which is clinically similar to Alzheimer's disease. Lewy bodies and Lewy neurites are made of abnormal filamentous material containing alpha-synuclein. Glial cytoplasmic inclusions in multiple system atrophy also contain alpha-synuclein. Using recombinant alpha-synuclein, we have produced synthetic filaments indistinguishable from those present in the intracellular inclusions of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Taken together, these findings indicate that Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are alpha-synucleinopathies.     

Topographical distribution of cerebral cortical thinning in patients with mild Parkinson's disease without dementia

The pathology of Parkinson's disease (PD) is not confined to the brainstem regions, but spreads to involve the neocortical areas. Using surface‐based cortical thickness analysis, we studied the topographical distribution of cortical thinning in nondemented patients with mild PD. The high‐resolution magnetic resonance imaging (MRI) studies were performed in 48 patients with PD without dementia and 56 age‐matched healthy controls. Using the Freesurfer software, surface‐based analysis was done to find changes in cerebral cortical thickness in patients with PD. Compared to the controls, patients with PD showed significant cortical thinning in the temporal, inferior parietal, rostral frontal, and orbitofrontal cortical areas. Thinning of the cerebral cortex occurs even in nondemented patients with mild PD, and its topographical distribution was similar to that of the neocortical Lewy bodies. Further studies are needed to find pathological and clinical correlates of thinned cerebral cortex found in nondemented patients with mild PD. © 2010 Movement Disorder Society     

Effects of rivastigmine in patients with and without visual hallucinations in dementia associated with Parkinson's disease

We aimed to determine prospectively whether rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, provided benefits in patients with and without visual hallucinations in a population with dementia associated with Parkinson's disease (PDD). This was a 24‐week double‐blind placebo‐controlled study. Primary efficacy measures were the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS‐cog) and Alzheimer's Disease Cooperative Study–Clinician's Global Impression of Change (ADCS‐CGIC). Secondary efficacy measures included activities of daily living, behavioral symptoms, and executive and attentional functions. Patients were stratified according to the presence of visual hallucinations at baseline. The study included 188 visual hallucinators (118 on rivastigmine, 70 on placebo) and 348 nonvisual hallucinators (239 on rivastigmine, 109 on placebo). Rivastigmine provided benefits in both visual hallucinators and nonvisual hallucinators. Absolute responses to rivastigmine on the ADAS‐cog were comparable over 6 months, although rivastigmine–placebo differences tended to be larger in visual hallucinators (4.27; P = 0.002) than in nonhallucinators (2.09; P = 0.015). On the ADCS‐CGIC, differences between rivastigmine and placebo were 0.5 in visual hallucinators (P = 0.030) and 0.3 in nonhallucinators (P = 0.111). Rivastigmine provided benefits on all secondary efficacy measures, and placebo declines and treatment differences were more marked in visual hallucinators. Adverse events were reported more frequently by rivastigmine‐treated patients, although this difference was less marked in visual hallucinators. Visual hallucinations appear to predict more rapid decline and possibly greater therapeutic benefit from rivastigmine treatment in PDD. © 2006 Movement Disorder Society