Mona K. Beyer

A magnetic resonance imaging study of patients with Parkinson’s disease with mild cognitive impairment and dementia using voxel-based morphometry

Background: Dementia is common in Parkinson’s disease, but the underlying brain pathology is not yet fully understood. Aim: To examine the changes in the brain of patients with Parkinson’s disease with mild cognitive impairment (MCI) and dementia, using structural magnetic resonance imaging. Methods: Using voxel-based morphometry, the grey matter atrophy on brain images of patients with Parkinson’s disease and dementia (PDD; n = 16) and Parkinson’s disease without dementia (PDND; n = 20), and healthy elderly subjects (n = 20) was studied. In the PDND group, 12 subjects had normal cognitive status and 8 had MCI. Standardised rating scales for motor, cognitive and psychiatric symptoms were used. Results: Widespread areas of cortical atrophy were found in patients with PDD compared with normal controls (in both temporal and frontal lobes and in the left parietal lobe). Grey matter reductions were found in frontal, parietal, limbic and temporal lobes in patients with PDD compared with those with PDND. In patients with PDND with MCI, areas of reduced grey matter in the left frontal and both temporal lobes were found. Conclusion: These findings show that dementia in Parkinson’s disease is associated with structural neocortical changes in the brain, and that cognitive impairment in patients with PDND may be associated with structural changes in the brain. Further studies with larger groups of patients are needed to confirm these findings.

GRAY MATTER ATROPHY IN PARKINSON DISEASE WITH DEMENTIA AND DEMENTIA WITH LEWY BODIES

Background: The nosologic relationship between dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) is continuously being debated. We conducted a study using voxel-based morphometry (VBM) to explore the pattern of cortical atrophy in DLB and PDD. Methods: Seventy-four patients and healthy elderly were imaged (healthy elderly n = 20, PDD n = 15, DLB n = 18, and Alzheimer dementia [AD] n = 21).Three dimensional T1-weighted MRI were acquired, and images analyzed using VBM. The following diagnostic criteria were used: criteria proposed by the third report of the DLB Consortium for DLB, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Diseases Association criteria for AD, and Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for dementia in PDD. Results: Overall dementia severity was similar in the dementia groups. We found more pronounced cortical atrophy in DLB than in PDD in the temporal, parietal, and occipital lobes. Patients with AD had reduced gray matter concentrations in the temporal lobes bilaterally, including the amygdala, compared to PDD. Compared to DLB, the AD group had temporal and frontal lobe atrophy. Conclusion: We found that despite a similar severity of dementia, patients with dementia with Lewy bodies (DLB) had more cortical atrophy than patients with Parkinson disease with dementia (PDD), indicating different brain substrates underlying dementia in the two syndromes. Together with previous studies reporting subtle clinical and neurobiologic differences between DLB and PDD, our findings support the hypothesis that PDD and DLB are not identical entities, but rather represent two subtypes of a spectrum of Lewy body disease.

Hippocampal, Caudate, and Ventricular Changes in Parkinson’s Disease with and Without Dementia

Parkinsons disease (PD) has been associated with mild cognitive impairment (PDMCI) and with dementia (PDD). Using radial distance mapping, we studied the 3D structural and volumetric differences between the hippocampi, caudates, and lateral ventricles in 20 cognitively normal elderly (NC), 12 cognitively normal PD (PDND), 8 PDMCI, and 15 PDD subjects and examined the associations between these structures and Unified Parkinsons Disease Rating Scale (UPDRS) Part III:motor subscale and Mini‐Mental State Examination (MMSE) performance. There were no hippocampal differences between the groups. 3D caudate statistical maps demonstrated significant left medial and lateral and right medial atrophy in the PDD vs. NC, and right medial and lateral caudate atrophy in PDD vs. PDND. PDMCI showed trend‐level significant left lateral caudate atrophy vs. NC. Both left and right ventricles were significantly larger in PDD relative to the NC and PDND with posterior (body/occipital horn) predominance. The magnitude of regionally significant between‐group differences in radial distance ranged between 20–30% for caudate and 5–20% for ventricles. UPDRS Part III:motor subscale score correlated with ventricular enlargement. MMSE showed significant correlation with expansion of the posterior lateral ventricles and trend‐level significant correlation with caudate head atrophy. Cognitive decline in PD is associated with anterior caudate atrophy and ventricular enlargement.

Visual rating of white matter hyperintensities in Parkinson's disease

Dementia is a common complication of Parkinsons disease (PD), but the cause is incompletely understood. In previous studies, dementia has been associated with an increase in hyperintense lesions in the cerebral white matter. The aim of this study was to explore whether white matter hyperintensities (WMH) on cerebral magnetic resonance imaging (MRI) are associated with dementia in PD. For this study, 35 patients with PD, 16 with dementia (PDD) and 19 without (PDND), and 20 control subjects were recruited. MRI scans of patients and controls were rated for WMH, blind to diagnosis, using the Scheltens visual rating scale. Both bivariate and multivariate statistical analyses were carried out. Cerebrovascular risk factors, education, gender, or age were similar across groups. Compared with the PDND group, the PDD group had significantly higher level of WMH in the deep white matter and in the periventricular areas. WMH in the deep white matter was the only variable that was associated significantly with Mini‐Mental State Examination score and explained 38% of the variance in the multivariate linear regression analysis. Our findings suggest that WMH in the deep white matter may contribute to dementia in PD.

Neuropsychiatric syndromes in patients with systemic lupus erythematosus and primary Sjögren syndrome: a comparative population-based study

Objectives: To compare the prevalence and pattern of neuropsychiatric (NP) syndromes observed in systemic lupus erythematosus (SLE) to patients with Primary Sjögren syndrome (PSS) using the American College of Rheumatology (ACR) criteria for the 19 NP syndromes seen in SLE. Methods: A population-based study was conducted including 68 patients with SLE (mean (SD) age 43.8 (13.6) years) and 72 with PSS (age 57.8 (13.0) years). Specialists in internal medicine, neurology and neuropsychology performed standardised examinations. Cerebral MRI scans and neurophysiological studies were performed in all patients. Results: Similar prevalences in SLE and PSS were observed for headaches (87% vs 78%, p = 0.165), cognitive dysfunction (46% vs 50%, p = 0.273), mood disorders (26% vs 33%, p = 0.376), anxiety disorders (12% vs 4%, p = 0.095), cranial neuropathy (1% vs 4%, p = 0.339) and seizure disorders (7% vs 3%, p = 0.208). Cerebrovascular disease was more common in SLE than PSS (12% vs 3%, p = 0.049); but mononeuropathy (0% vs 8%, p = 0.015) and polyneuropathy (18% vs 56%, p<0.001) were less common in SLE than PSS. Other syndromes were rare or absent in both patient groups. Conclusions: Headache, cognitive dysfunction and mood disorders are common in both diseases, but otherwise there are distinct differences in NP involvement, with cerebrovascular diseases more prevalent in SLE and neuropathies more common in PSS. This indicates that some NP disease mechanisms are shared while others differ between the two diseases.

Dementia in Parkinson's disease

Purpose of reviewCognitive impairment and dementia are among the most common nonmotor changes in Parkinsons disease. The purpose of this review is to present recent findings of clinical and neurobiological aspects of dementia in Parkinsons disease. Recent findingsNew consensus criteria for a clinical diagnosis of dementia in Parkinsons disease have been proposed. A very high cumulative prevalence of dementia in Parkinsons disease has been shown in two independent long-term cohorts. Mild cognitive impairment occurs even in early Parkinsons disease and is associated with a shorter time to dementia. Emerging evidence from pathology, as well as in-vivo studies using novel techniques within genetics, imaging, and cerebrospinal fluid research, indicates that α-synuclein aggregation and disturbances of other candidate proteins are associated with dementia in Parkinsons disease. Clinical, pathological, and electrophysiological studies support the hypothesis of different subtypes of dementia in Parkinsons disease, potentially related to different underlying brain changes. SummaryIncreased understanding of underlying mechanisms of cognitive decline and dementia in Parkinsons disease has been achieved. This will hopefully lead to novel treatment with the potential of preventing or delaying the onset of dementia by influencing these mechanisms.

Gray matter correlations of cognition in incident Parkinson's disease

We aimed to investigate whether mild cognitive impairment (MCI) in Parkinsons disease (PD) is characterized by region‐specific gray matter (GM) atrophy and to explore correlations between GM and cognition in PD. Magnetic resonance images of 42 newly diagnosed PD patients (of which 11 had MCI) and 37 normal controls were analyzed using voxel‐based morphometry. Analyses comparing groups showed no regional atrophy, and in patients there were no significant correlations between cognitive domain test performance and GM loss. In conclusion, GM atrophy does not seem to be a major feature of cognitive dysfunction in incident PD.

Cortical thickness and surface area relate to specific symptoms in early relapsing–remitting multiple sclerosis:

Background: Cortical atrophy is common in early relapsing–remitting multiple sclerosis (RRMS). Whether this atrophy is caused by changes in cortical thickness or cortical surface area is not known, nor is their separate contributions to clinical symptoms. Objectives: To investigate the difference in cortical surface area, thickness and volume between early RRMS patients and healthy controls; and the relationship between these measures and neurological disability, cognitive decline, fatigue and depression. Methods: RRMS patients (n = 61) underwent magnetic resonance imaging (MRI), neurological and neuropsychological examinations. We estimated cortical surface area, thickness and volume and compared them with matched healthy controls (n = 61). We estimated the correlations between clinical symptoms and cortical measures within the patient group. Results: We found no differences in cortical surface area, but widespread differences in cortical thickness and volume between the groups. Neurological disability was related to regionally smaller cortical thickness and volume. Better verbal memory was related to regionally larger surface area; and better visuo-spatial memory, to regionally larger cortical volume. Higher depression scores and fatigue were associated with regionally smaller cortical surface area and volume. Conclusions: We found that cortical thickness, but not cortical surface area, is affected in early RRMS. We identified specific structural correlates to the main clinical symptoms in early RRMS.

White matter hyperintensities do not impact cognitive function in patients with newly diagnosed Parkinson's disease.

The objective of this study was to investigate total volume and spatial distribution of white matter hyperintensities (WMH) in a large sample of newly diagnosed Parkinsons disease (PD) patients with and without mild cognitive impairment (MCI) compared to normal controls (NC). Furthermore, we aimed to examine the impact of the WMH on attention-executive performance in PD. MCI is regarded as a pre-dementia stage. Studies on MCI have found WMH associated with reduced cognitive function, especially in the attention and executive domains. The present study included 163 incident, drug-naïve PD patients (66.2+/-9.1 years and disease duration 27.1+/-19.8 months) and 102 age-matched NC (65.7+/-9.4 years). Thirty (30) subjects in the PD sample presented MCI, whereas 133 did not. MCI was classified based on tests for memory, attention-executive and visuospatial function compared to the NC group, taking age, sex and education into consideration. WMH were outlined on FLAIR scans using a semi-automated technique. Total WMH volumes were compared between the 3 study groups, and spatial distribution of normalized WMH masks in each group were compared using voxel-wise probability maps. Regression analysis examined the possible impact of WMH on attention-executive scores in the PD group. Analysis showed that there were no significant differences between the 3 groups in total volume or spatial distribution of WMH. In addition there was no significant relationship between total volume or spatial distribution of WMH and attention-executive functions in PD. We conclude that in this PD cohort, cognitive impairment seems to be independent of WMH damage.

Verbal memory is associated with structural hippocampal changes in newly diagnosed Parkinson's disease

Background and objective Cognitive impairment, including impairment of episodic memory, is frequently found in newly diagnosed Parkinsons disease (PD). In this longitudinal observational study we investigated whether performance in memory encoding, retention, recognition and free recall is associated with reduced hippocampal radial distance. Methods We analysed baseline T1-weighted brain MRI data from 114 PD subjects without cognitive impairment, 29 PD subjects with mild cognitive impairment and 99 normal controls from the ParkWest study. Age- and education-predicted scores for the California Verbal Learning Test 2 (CVLT-2) and tests of executive function were regressed against hippocampal radial distance while adjusting for imaging centre. Results There was no association between encoding or performance on executive tests and hippocampal atrophy in the PD group. In the full PD sample we found bilaterally significant associations between lower delayed free recall scores and hippocampal atrophy in the CA1, CA3 and subiculum area (left, p=0.0013; right, p=0.0082). CVLT-2 short delay free recall scores were associated with bilateral hippocampal CA1 and subicular atrophy in the full PD sample (left, p=0.013; right, p=0.047). CVLT-2 recognition scores showed a significant association with right-sided subicular and CA1 atrophy in the full PD sample (p=0.043). Conclusions At the time of PD diagnosis, subjects’ verbal memory performance in recall and recognition are associated with atrophy of the hippocampus, while encoding is not associated with hippocampal radial distance. We postulate that impaired recall and recognition might reflect deficient memory consolidation at least partly due to structural hippocampal changes.