Jellemer Jolles

Bio: Jellemer Jolles is an academic researcher from Maastricht University. The author has contributed to research in topics: Dementia & Cognitive decline. The author has an hindex of 50, co-authored 108 publications receiving 14058 citations. Previous affiliations of Jellemer Jolles include Utrecht University.

Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study

Abstract: OBJECTIVE—White matter lesions are often seen on MR scans of elderly non-demented and demented people. They are attributed to degenerative changes of small vessels and are implicated in the pathogenesis of cognitive decline and dementia. There is evidence that especially periventricular white matter lesions are related to cognitive decline, whereas subcortical white matter lesions may be related to late onset depression. The frequency distribution of subcortical and periventricular white matter lesions according to age and sex reported. METHODS—A total of 1077 subjects aged between 60-90 years were randomly sampled from the general population. All subjects underwent 1.5T MR scanning; white matter lesions were rated separately for the subcortical region and the periventricular region. RESULTS—Of all subjects 8% were completely free of subcortical white matter lesions, 20% had no periventricular white matter lesions, and 5% had no white matter lesions in either of these locations. The proportion with white matter lesions increased with age, similarly for men and women. Women tended to have more subcortical white matter lesions than men (total volume 1.45 ml v 1.29 ml; p=0.33), mainly caused by marked differences in the frontal white matter lesion volume (0.89 ml v 0.70 ml; p=0.08). Periventricular white matter lesions were also more frequent among women than men (mean grade 2.5 v 2.3; p=0.07). Also severe degrees of subcortical white matter lesions were more common in women than in men (OR 1.1; 95% confidence interval (95% CI) 0.8-1.5) and periventricular white matter lesions (OR 1.2; 95% CI 0.9-1.7), albeit that none of these findings were statistically significant. CONCLUSIONS—The prevalence and the degree of cerebral white matter lesions increased with age. Women tended to have a higher degree of white matter lesions than men. This may underlie the finding of a higher incidence of dementia in women than in men, particularly at later age.

Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study.

Abstract: Cerebral white matter lesions (WMLs) have been associated with cognitive dysfunction. Whether periventricular or subcortical WMLs relate differently to cognitive function is still uncertain. In addition, it is unclear whether WMLs are related to specific cognitive domains such as memory or psychomotor speed. We examined the relationship between periventricular and subcortical WMLs and cognitive functioning in 1,077 elderly subjects randomly sampled from the general population. Quantification of WMLs was assessed by means of an extensive rating scale on 1.5-T magnetic resonance imaging scans. Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed, memory performance, and global cognitive function. When analyzed separately, both periventricular and subcortical WMLs were related to all neuropsychological measures. When periventricular WMLs were analyzed conditional on subcortical WMLs and vice versa, the relationship between periventricular WMLs and global cognitive function remained unaltered whereas the relationship with subcortical WMLs disappeared. Subjects with most severe periventricular WMLs performed nearly 1 SD below average on tasks involving psychomotor speed, and more than 0.5 SD below average for global cognitive function. Tasks that involve speed of cognitive processes appear to be more affected by WMLs than memory tasks.

Cerebral small-vessel disease and decline in information processing speed, executive function and memory

Abstract: Cerebral small-vessel disease is common in older people and may contribute to the development of dementia The objective of the present study was to evaluate the relationship between measures of cerebral small-vessel disease on MRI and the rate of decline in specific cognitive domains in participants from the prospective, population-based Rotterdam Scan Study Participants were 60-90 years of age and free from dementia at baseline in 1995-1996 White matter lesions (WML), cerebral infarcts and generalized brain atrophy were assessed on the baseline MRI We performed neuropsychological testing at baseline and repeatedly in 1999-2000 and in 2001-2003 We used random-effects models for repeated measures to examine the association between quantitative MRI measures and rate of decline in measures of global cognitive function, information processing speed, executive function and memory There were a total of 2266 assessments for the 832 participants in the study, with an average time from the initial to last assessment of 52 years Increasing severity of periventricular WML and generalized brain atrophy and the presence of brain infarcts on MRI were associated with a steeper decline in cognitive function These structural brain changes were specifically associated with decline in information processing speed and executive function The associations between MRI measures of cerebral small-vessel disease and cognitive decline did not change after additional adjustment for vascular risk factors or depressed mood After exclusion of participants with an incident stroke, some of the associations of periventricular WML, brain infarcts and generalized brain atrophy with measures of information processing speed and executive function were no longer significant This may indicate that stroke plays an intermediate role in the relationship between cerebral small-vessel disease and cognitive decline Our results suggest that in older people cerebral small-vessel disease may contribute to cognitive decline by affecting information processing speed and executive function

Studies and perspectives of protein kinase C

Abstract: Protein kinase C, an enzyme that is activated by the receptor-mediated hydrolysis of inositol phospholipids, relays information in the form of a variety of extracellular signals across the membrane to regulate many Ca2+-dependent processes. At an early phase of cellular responses, the enzyme appears to have a dual effect, providing positive forward as well as negative feedback controls over various steps of its own and other signaling pathways, such as the receptors that are coupled to inositol phospholipid hydrolysis and those of some growth factors. In biological systems, a positive signal is frequently followed by immediate negative feedback regulation. Such a novel role of this protein kinase system seems to give a logical basis for clarifying the biochemical mechanism of signal transduction, and to add a new dimension essential to our understanding of cell-to-cell communication.

Regression Diagnostics: Identifying Influential Data and Sources of Collinearity

Abstract: 1. Introduction and Overview. 2. Detecting Influential Observations and Outliers. 3. Detecting and Assessing Collinearity. 4. Applications and Remedies. 5. Research Issues and Directions for Extensions. Bibliography. Author Index. Subject Index.

Parkinson’s disease: clinical features and diagnosis

Abstract: Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria

Abstract: The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid beta as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.