Development Of Dementia In Patients Research Articles

THE EFFECTS OF HOME-BASED COGNITIVE INTERVENTION WITH ROBOTS ON COGNITIVE PERFORMANCE IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT

Previous studies showed that cognitive intervention helped mitigating the development of dementia in patients with mild cognitive impairment (MCI). However, the cognitive intervention programs of the previous studies were mostly provided as a group-session in a local hospital, which often made patients with MCI having difficulty in regularly attending sessions or reluctant to participate in group-based classes. In addition, traditional cognitive intervention usually needs experienced instructors, but those qualified instructors may be unavailable in some chronic care facilities or community centers. For this reason, we have developed a total of 20 programs for home-based cognitive intervention with robots for the patients with MCI. The purpose of this study was to demonstrate the effects of our newly developed home-based cognitive training with robots on the cognitive performance in patients with MCI. A single-blind randomized controlled trial was conducted in 48 volunteers aged 60 years or older with mild cognitive impairment. Participants were randomized into two groups: 24 with robot intervention, and 24 without cognitive training. The interventions consisted of 60-min-session per day for 4 weeks. The primary outcome was the changes in cognitive function measured by Cambridge Neuropsychological Test Automated Battery. There were no demographic differences between the robot intervention and the control groups. The robot intervention group showed a greater improvement in the attention function than the control group after 4-week training. Our home-based cognitive training with robots helped improve attention in patients with MCI. The further study with larger samples for a longer duration would be warranted to demonstrate the effects of those programs in other cognitive domains in MCI patients.

Association of glucocerebrosidase polymorphisms and mutations with dementia in incident Parkinson's disease

IntroductionBoth polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease. MethodsFour hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis. ResultsA total of 12.0% of patients with Parkinson's disease carried a GBA variant, and nearly half (22/53) of them progressed to dementia during follow-up. Carriers of deleterious GBA mutations (adjusted hazard ratio 3.81, 95% confidence interval 1.35 to 10.72; P = .011) or polymorphisms (adjusted hazard ratio 1.79; 95% confidence interval 1.07 to 3.00; P = .028) progressed to dementia more rapidly than noncarriers. DiscussionGBA variants are of great clinical relevance for the development of dementia in Parkinson's disease, especially due to the relatively higher frequency of these alleles compared with other risk alleles.

Thiamine for preventing dementia development among patients with alcohol use disorder: A nationwide population-based cohort study

Alcohol use disorder is one of the most important factors contributing to dementia. This study examined the protective effect of thiamine administration on the incidence of dementia among patients with alcohol use disorder in Taiwan by evaluating a nationwide database. We retrieved data for this retrospective cohort study from the Longitudinal Health Insurance Database 1995-2000. Patients receiving thiamine therapy after the diagnosis of alcohol use disorder were recruited as the thiamine therapy (TT) group, and the comparison group without TT (NTT group) included randomly assigned and age-, sex-, and index year-matched individuals with alcohol use disorder. Demographic data, comorbid medical disorders, and psychotropic medication use were evaluated and controlled. The cumulative defined daily dose (DDD) was analyzed to demonstrate the dose effect. Each group had 5059 patients. The TT group had a lower crude hazard ratio (0.76; 95% confidence interval: 0.60-0.96) of dementia than the NTT group. After adjusting for demographic data, comorbidity, and psychotropic medication use, the adjusted hazard ratio was 0.54 (95% confidence interval: 0.43-0.69). The significance existed among TT subjects with cumulative DDD higher than 23. The Kaplan-Meier analysis demonstrated a lower cumulative incidence of dementia in the TT group than in the NTT group. The results indicated that thiamine therapy could be a protective factor for dementia development in patients with alcohol use disorder. Thiamine therapy should be a crucial part of the treatment plan and health policies to prevent dementia development or progression among patients with alcohol use disorder.

Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections-a Nationwide, Population-Based Cohort Study in Taiwan.

This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using Taiwan's National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2000. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing dementia in the HSV cohort. This analysis revealed an adjusted hazard ratio of 2.564 (95% CI: 2.351-2.795, P < 0.001) for the development of dementia in the HSV-infected cohort relative to the non-HSV cohort. Thus, patients with HSV infections may have a 2.56-fold increased risk of developing dementia. A risk reduction of dementia development in patients affected by HSV infections was found upon treatment with anti-herpetic medications (adjusted HR = 0.092 [95% CI 0.079-0.108], P < 0.001). The usage of anti-herpetic medications in the treatment of HSV infections was associated with a decreased risk of dementia. These findings could be a signal to clinicians caring for patients with HSV infections. Further research is, therefore, necessary to explore the underlying mechanism(s) of these associations.

Development of dementia in patients with femoral neck fracture who experience postoperative delirium-A three-year follow-up study.

It remains unclear to what extent postoperative delirium (POD) affects the incidence of dementia in hip fracture patients, and the methods used to detect delirium and dementia require validation. The aim of this study was to investigate the development of dementia within 3years of femoral neck fracture repair surgery, with a focus on POD as a potential predictive factor. Patients were assessed for cognition, delirium, depression, psychological well-being, and nutritional status during their hospitalization as well as 4, 12, and 36months after the operation. Logistic regression models were used to analyse factors associated with POD and factors associated with the development of dementia. The study sample consisted of 135 patients without a history of dementia, of whom 20 (14.8%) were delirious preoperatively and 75 (55.5%) postoperatively. Three years after their operations, 43/135 patients (31.8%) were diagnosed with dementia. A greater portion of patients diagnosed with dementia (39/43, 90.6%) than patients with no dementia (36/92, 39.1%) were included among the 75 patients who had experienced POD (P<0.001). In a logistic regression model, after adjustment for covariates (age, sex, diabetes, delirium pre-and postoperatively, hyperactive delirium, days with delirium, urinary tract infection, and Mini Nutritional Assessment score), POD emerged an independent predictor for the development of new dementia (odds ratio, 15.6; 95% confidence interval, 2.6-91.6) within 3years after the operation. Geriatric hip fracture patients who exhibit POD should be monitored closely for the development of dementia.

Subcortical shape analysis of progressive mild cognitive impairment in Parkinson's disease.

Cortical neural correlates of ongoing cognitive decline in Parkinson's disease (PD) have been suggested; however, the role of subcortical structures in longitudinal change of cognitive dysfunction in PD has not been fully investigated. Here, we used automatic analysis to explore subcortical brain structures in patients with PD with mild cognitive impairment that converts into PD with dementia. One hundred eighty-two patients with PD with mild cognitive impairment were classified as PD with mild cognitive impairment converters (n = 74) or nonconverters (n = 108), depending on whether they were subsequently diagnosed with dementia in PD. We used surface-based analysis to compare atrophic changes of subcortical brain structures between PD with mild cognitive impairment converters and nonconverters. PD with mild cognitive impairment converters had lower cognitive composite scores in the attention and frontal executive domains than did nonconverters. Subcortical shape analysis revealed that PD with mild cognitive impairment converters had smaller local shape volumes than did nonconverters in the bilateral thalamus, right caudate, and right hippocampus. Logistic regression analysis showed that local shape volumes in the bilateral thalamus and right caudate were significant independent predictors of PD with mild cognitive impairment converters. In the PD with mild cognitive impairment converter group, thalamic local shape volume was associated with semantic fluency and attentional composite score. The present data suggest that the local shape volumes of deep subcortical structures, especially in the caudate and thalamus, may serve as important predictors of the development of dementia in patients with PD. © 2017 International Parkinson and Movement Disorder Society.

Dementia-Free Survival and Risk Factors for Dementia in a Hospital-Based Korean Parkinson's Disease Cohort.

Background and PurposeFew studies of dementia in Parkinson's disease (PD) have had long-term follow-ups. Moreover, information on the duration from the onset to the development of dementia in patients with PD is lacking. The aim of this study was to determine the median dementia-free survival time from the onset of PD to the development of dementia.MethodsIn total, 1,193 Korean patients with PD were recruited and assessed at regular intervals of 3–6 months. We interviewed the patients and other informants to identify impairments in the activities of daily living. The Hoehn and Yahr stage and scores on the Unified Parkinson's Disease Rating Scale and Mini Mental State Examination were evaluated annually. We used Kaplan-Meier survival analysis to estimate the cumulative proportion of dementia-free patients over time. Risk factors predicting dementia were also evaluated using Cox proportional-hazards regression models.ResultsThe median dementia-free survival time in the Korean PD population was 19.9 years. Among the 119 patients who subsequently developed dementia, the mean duration from the onset of PD to the development of dementia was 10.6 years. A multivariate analysis identified age at onset and education period as the significant predictors of dementia.ConclusionsThis is the first report on dementia-free survival in patients with PD based on longitudinal data analysis from the disease onset. The median dementia-free survival time in Korean PD patients was found to be longer than expected.

Hippocampal Lewy pathology and cholinergic dysfunction are associated with dementia in Parkinson's disease.

The neuropathological substrate of dementia in patients with Parkinson's disease is still under debate, particularly in patients with insufficient alternate neuropathology for other degenerative dementias. In patients with pure Lewy body Parkinson's disease, previous post-mortem studies have shown that dopaminergic and cholinergic regulatory projection systems degenerate, but the exact pathways that may explain the development of dementia in patients with Parkinson's disease remain unclear. Studies in rodents suggest that both the mesocorticolimbic dopaminergic and septohippocampal cholinergic pathways may functionally interact to regulate certain aspects of cognition, however, whether such an interaction occurs in humans is still poorly understood. In this study, we performed stereological analyses of the A9 and A10 dopaminergic neurons and Ch1, Ch2 and Ch4 cholinergic neurons located in the basal forebrain, along with an assessment of α-synuclein pathology in these regions and in the hippocampus of six demented and five non-demented patients with Parkinson's disease and five age-matched control individuals with no signs of neurological disease. Moreover, we measured choline acetyltransferase activity in the hippocampus and frontal cortex of eight demented and eight non-demented patients with Parkinson's disease, as well as in the same areas of eight age-matched controls. All patients with Parkinson's disease exhibited a similar 80-85% loss of pigmented A9 dopaminergic neurons, whereas patients with Parkinson's disease dementia presented an additional loss in the lateral part of A10 dopaminergic neurons as well as Ch4 nucleus basalis neurons. In contrast, medial A10 dopaminergic neurons and Ch1 and Ch2 cholinergic septal neurons were largely spared. Despite variable Ch4 cell loss, cortical but not hippocampal cholinergic activity was consistently reduced in all patients with Parkinson's disease, suggesting significant dysfunction in cortical cholinergic pathways before frank neuronal degeneration. Patients with Parkinson's disease dementia were differentiated by a significant reduction in hippocampal cholinergic activity, by a significant loss of non-pigmented lateral A10 dopaminergic neurons and Ch4 cholinergic neurons (30 and 55% cell loss, respectively, compared with neuronal preservation in control subjects), and by an increase in the severity of α-synuclein pathology in the basal forebrain and hippocampus. Overall, these results point to increasing α-synuclein deposition and hippocampal dysfunction in a setting of more widespread degeneration of cortical dopaminergic and cholinergic pathways as contributing to the dementia occurring in patients with pure Parkinson's disease. Furthermore, our findings support the concept that α-synuclein deposition is associated with significant neuronal dysfunction in the absence of frank neuronal loss in Parkinson's disease.

Predictors of dementia in Parkinson's disease; findings from a 5-year prospective study using the SCOPA-COG.

Aim of this study was to identify risk factors for the development of dementia in patients with Parkinson's disease (PD). A broad range of motor and non-motor features was assessed at baseline and the following five years in 406 PD patients. Cross-sectional analyses of baseline data and longitudinal analyses of follow-up data were performed to identify risk factors for dementia. Thirty-two percent of patients (n = 129) had dementia at baseline, while 26% of patients (n = 68) without dementia at baseline developed dementia during follow-up. Univariate survival analysis showed that higher age, fewer years of education, longer disease duration, higher age-at-onset, higher levodopa dose, higher Hoehn & Yahr stage, presence of dyskinesias, excessive daytime sleepiness (EDS), presence of hallucinations, and more severe autonomic and depressive symptoms were associated with an increased risk of dementia. Higher baseline Postural-Instability-and-Gait-Difficulty scores were also associated with an increased risk of dementia, whereas no effect of tremor severity was found. These findings largely corresponded with the variables that were associated with the presence of dementia at baseline. In a stepwise regression model, higher age at baseline, fewer years of education, higher daily levodopa dose and excessive daytime sleepiness (EDS) emerged as independent risk factors of future dementia. In this large prospective cohort study, we identified a combination of potentially interacting risk factors for dementia in PD that are associated with higher age and more advanced disease.

Dementia and cognitive impairment in patients with Parkinson's disease from India: a 7-year prospective study.

Depression and cognitive impairment are frequent manifestations in Parkinson's disease (PD). Although a few longitudinal studies have reported on depression and dementia in PD, there is a yet a lack of such studies in India. This 7-year longitudinal study is a hospital-based prospective case (n = 250)-control (n = 280) study. In all, 36.8% had PD with no cognitive impairment (PD-Normal), 27.2% of the patients with PD were affected by dementia (PDD), and 36% of the remaining patients with PD had mild cognitive impairment (PD-MCI) at baseline. After 7 years of evaluation, 32 new patients, 12 patients from the PD-MCI group and 9 patients from the PD-Normal group, were diagnosed with dementia. The 7-year prevalence rate for dementia was estimated to be 49.28%. In the Indian population, an early onset of dementia is noted among patients with PD, with the age of onset being less than 55 years. Patients with early-onset PDD showed depression symptoms that differed significantly from the controls of the same age-group. There was a major difference in verbal fluency, word list recall, constructional praxis and recall, word list recognition, abridged Boston Naming Test, word list memory with repetition, and Mini-Mental State Examination between PD-MCI and PDD groups. Hallucinations before baseline (odds ratio [OR] = 4.427, 95% confidence interval [CI] = 2.122-9.373), akinetic/tremor dominancy (OR = 0.380, 95%CI = 0.149-0.953), and asymmetrical disease onset (OR = 0.3285, 95%CI = 0.1576-0.685) can be considered as risk factors for patients with dementia. Patients with early-onset PD might be more prone to complex depression and dementia. As the disease progresses, akinetic-dominant PD, early hallucinations, and asymmetrical disease onset are the potential risk factors for the development of dementia in patients with PD.

Prostaglandin D2 synthase: Apoptotic factor in alzheimer plasma, inducer of reactive oxygen species, inflammatory cytokines and dialysis dementia.

Apoptosis, reactive oxygen species (ROS) and inflammatory cytokines have all been implicated in the development of Alzheimer's disease (AD). The present study identifies the apoptotic factor that was responsible for the fourfold increase in apoptotic rates that we previously noted when pig proximal tubule, LLC-PK1, cells were exposed to AD plasma as compared to plasma from normal controls and multi-infarct dementia. The apoptotic factor was isolated from AD urine and identified as lipocalin-type prostaglandin D2 synthase (L-PGDS). L-PGDS was found to be the major apoptotic factor in AD plasma as determined by inhibition of apoptosis approximating control levels by the cyclo-oxygenase (COX) 2 inhibitor, NS398, and the antibody to L-PGDS. Blood levels of L-PGDS, however, were not elevated in AD. We now demonstrate a receptor-mediated uptake of L-PGDS in PC12 neuronal cells that was time, dose and temperature-dependent and was saturable by competition with cold L-PGDS and albumin. Further proof of this endocytosis was provided by an electron microscopic study of gold labeled L-PGDS and immunofluorescence with Alexa-labeled L-PGDS. The recombinant L-PGDS and wild type (WT) L-PGDS increased ROS but only the WTL-PGDS increased IL6 and TNFα, suggesting that differences in glycosylation of L-PGDS in AD was responsible for this discrepancy. These data collectively suggest that L-PGDS might play an important role in the development of dementia in patients on dialysis and of AD.

Is Neuroinflammation Involved in the Development of Dementia in Patients with Parkinson's Disease?

High-sensitivity C-reactive protein (hs-CRP) is an extremely sensitive systemic marker of inflammation and tissue damage, and increased levels of hs-CRP are strongly associated with inflammatory reactions. Microglia-mediated neuroinflammation has been hypothesized to play an important role in the pathogenesis of idiopathic Parkinson's disease (PD). However, the clinical value of the hs-CRP level in patients with PD is poorly defined. Therefore, we conducted this study to analyze the differences in the hs-CRP levels in PD patients with and without dementia. We examined 72 PD patients without dementia (PDwoD) and 45 PD patients with dementia (PDD), as well as 84 control subjects. We investigated the differences in the hs-CRP and fibrinogen levels between these three groups. The mean hs-CRP and fibrinogen values were not significantly different between the PDwoD and PDD groups; however, these two groups had significantly higher mean hs-CRP and fibrinogen values than the control group. It is known that inflammation plays a role in the pathogenesis of PD and dementia. However, based on the results of this study, we cautiously speculate that although neuroinflammation plays a role in the development of neurodegenerative diseases, including PD and dementia, it may be unrelated to the pathogenesis of dementia in patients with PD.

Antihypertensive treatment can prevent stroke and cognitive decline

Hypertension is a highly prevalent risk factor for stroke and dementia, and is the greatest risk factor for small-vessel disease-a frequent cause of lacunar infarction and intracerebral haemorrhage. Lacunar and cortical strokes contribute to the development of dementia in patients with, and in those without, Alzheimer disease pathology; this relationship between stroke and dementia is probably mediated by ischaemia-induced neuroinflammation. Antihypertensive treatment can reduce the risk of stroke and dementia, but requires optimal blood pressure targets to be established for individual patients. Although the rate of treatment and control of hypertension has improved markedly over the past two decades, many physicians remain reluctant to prescribe antihypertensive medication to elderly patients owing to potential adverse events such as cardiovascular morbidity and postural hypotension. In this article we argue that, in patients of all ages, not treating hypertension is a missed opportunity to prevent some of the most prevalent brain diseases.

Clinical significance of REM sleep behavior disorder in Parkinson’s disease

Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for dementia development in patients with Parkinson's disease (PD); however, the role of subclinical RBD remains unknown. Patients with PD and clinical RBD, subclinical RBD, or with normal REM sleep were examined in a cross sectional study and a longitudinal follow-up. Interviews regarding RBD symptoms and polysomnographies were performed on 82 PD patients divided into RBD subcategories based on the presence/absence of REM sleep without atonia (RWA) and/or RBD symptoms. Descriptive variables were compared and patients were followed-up longitudinally for 21.4±10.8months. The existence of RBD, but not subclinical RBD, was associated with orthostatic hypotension and levodopa dose equivalents (LDEs) in patients with PD. Kaplan-Myer curves indicated that the occurrence of dementia in the PD group with clinical RBD was significantly faster than in the PD group with normal REM sleep (p=0.013). A Cox hazard regression analysis revealed that development to PD with dementia was only significantly associated with the presence of clinical RBD (hazard ratio: 14.1, p=0.017). Clinical RBD symptoms, but not subclinical RBD, were associated with the development of dementia in PD.

Neurodegeneration, β‐amyloid and mood disorders: state of the art and future perspectives

Depression may increase the risk of developing Alzheimer's disease (AD). Recent studies have shown modifications in blood beta-amyloid (Aβ) levels in depressed patients. This literature review examines the potential relationship between Aβ-mediated neurotoxicity and pathophysiology of mood disorders. We conducted a review of the literature focusing on recent studies reporting alterations of plasma and serum Aβ peptides levels in patients suffering from mood disorders. Different data suggest that patients with mood disorders are at great risk of developing cognitive impairment and dementia. In particular, low plasma levels of Aβ42 peptide and a high Aβ40/Aβ42 ratio have been found in depressed patients. In addition, changes in Aβ protein levels in patients with mood disorders have been associated with the severity of cognitive impairment and correlated positively with the number of episodes and severity of illness course. Given the intriguing association between change in plasma level of Aβ, depression and cognitive impairment, future work should focus on the relationship between Aβ peripheral level(s), biomarkers of neurodegeneration and development of dementia in patients affected by mood disorders.

Cognitive Impairment and Seizures in Patients with Lacunar Strokes

Lacunar strokes are mainly related to cerebral microangiopathy and to the presence of leukoaraiosis. Cognitive impairment is frequently linked to the presence of lacunes and white matter changes. The cognitive impairment consists mainly of disturbances of executive functions sometimes leading to dementia. It is mainly due to interruption of the frontal-subcortical neuronal circuits. Seizures are also observed in patients with lacunes and white matter changes. Although lacunes cannot be considered as the cause of the seizures, there is a relationship between the occurrence of cognitive impairment and seizures. Repeated seizures promote further cognitive decline. However, the development of dementia in patients with late-onset epilepsy is most probably not directly due to the lacunes but rather due to Alzheimer's disease or to cortical cerebrovascular lesions. The development of lacunes should only be the aggravating factor for the cognitive decline as demonstrated in the Nun study.

Mild Cognitive Impairment: Beyond Memory Dysfunction

Traditionally, mild cognitive impairment (MCI) has tended to be primarily characterised and diagnosed in relation to the integrity of amnestic function and thus studied accordingly. However, a more recent multidisciplinary and collaborative research approach has investigated a much wider range of cognitive, functional, structural, and behavioural integrity and is revealing an extensive and often complex range of characteristics in addition to memory dysfunction that differentiate MCI from healthy ageing. These may be of especial relevance when considering MCI as a potential prodromal stage of dementia. Several papers in this special issue report novel and important findings with respect to the search for predictors of development of dementia in patients with MCI. The paper by E. L. Abner et al. describes a new approach in the assessment of risk factors for dementia, including age, gender, education, apolipoprotein E status, family history of dementing illness, and baseline hypertension. Their results highlight the importance of objective criteria in MCI diagnosis. I. Reinvang et al. report on how studies of genetic high-risk groups, using sensitive cognitive neuroscience paradigms, indicate the potential for differences in executive function to be a cognitive marker useful for tracking development of the pathophysiological changes of Alzheimer’s disease (AD). The paper by D. V. Moretti et al. reveals specific electroencephalographic (EEG) changes associated with atrophy of the hippocampus in people with MCI and AD, namely, that the increase of alpha3/alpha2 power ratio is correlated with atrophy of the hippocampus both in MCI and in AD patients, suggesting a possible diagnostic role of EEG markers. In a comprehensive review, B. Ferencz et al. provide an overview of brain changes in early AD and MCI, together with evidence for recent advances in neuroimaging and genetic biomarkers and the importance of altered mitochondrial dynamics in the preclinical stages of AD. D. P. Devanand et al. discuss the outcome of their detailed and novel study that uses clinical and magnetic resonance imaging (MRI) variables to compare predictor models for the transition to AD in patients with MCI. Research priority has until relatively recently been directed to the amnestic type of mild cognitive impairment (aMCI). However, the paper by A. Poggesi et al. provides an important overview of the concept of vascular MCI and how it may signal the prodromal stages of vascular dementia or the presence of small vessel disease. It is of course important to raise awareness of MCI within the public at large and also to determine the factors likely to encourage individuals to report a change in their memory to their general practitioner. C. Pires et al. highlight the importance of the type of memory complaint in determining whether an individual seeks medical attention and describe how forgetting the name of family members or friends is a particularly strong impetus for such contact. Increasingly, studies are addressing the potential of MCI to adversely affect a wide range of factors that impinge upon an individual’s quality of life. In the paper by G. Arsenault-Lapierre et al., the importance of stress in the lives of those with MCI and dementia is described, together with the finding that patients with MCI or dementia can display anosognosia, which can preclude patients from accurately appraising their own level of stress. Together these papers contribute to our further understanding of the concept of MCI and of its potential progression to dementia. All highlight the need to think beyond merely memory dysfunction in MCI and to continue to expand our knowledge in this important field of scientific and clinical research.

Plasma C-reactive protein is related to cognitive deterioration and dementia in patients with mild cognitive impairment

ObjectiveTo investigate the relationship between plasma C-reactive protein (CRP) and the risk for cognitive deterioration and development of dementia in patients with mild cognitive impairment (MCI). MethodsElderly Chinese patients with suspected cognitive impairment were screened. A total of 168 patients who met the criteria for MCI were enrolled. Plasma CRP levels were measured at baseline. The global cognitive functions were assessed at baseline and during follow-up periodically with Mini-Mental State Examination (MMSE). All enrolled patients were followed and evaluated regularly for 2 years to determine if the patients developed dementia. ResultsOf the 168 patients with MCI diagnosed at baseline, 14 (8.3%) deceased, 13 (7.7%) lost to follow-up, and 58 (34.5%) developed dementia during follow-up. MMSE score of the enrolled patients declined significantly during follow-up (22.1±3.0 vs 18.6±5.5, P<0.001). MMSE score was significantly lower for the patients with high CRP levels than that for those with low plasma CRP levels (−4.9±5.4 vs −3.2±4.2, P<0.05). Patients with high plasma CRP level had an increased risk for dementia and vascular dementia as compared with patients with low level of plasma CRP (Log rank test, P<0.05). ConclusionHigh plasma CRP level was associated with accelerated cognitive decline and increased risk for dementia in patients with MCI.

The Relationship of Parkinson Disease With Aging

Twentieth-century hypotheses attributing a substantive role to aging in Parkinson disease (PD) pathogenesis have been countered by evidence from clinical, pathological, and biochemical investigations. However, age influences the clinical progression of PD. Several studies have demonstrated that advancing age is associated with a faster rate of motor progression, decreased levodopa responsiveness, more severe gait and postural impairment, and more severe cognitive impairment and the development of dementia in patients with PD. A model for the relationship between PD and aging is proposed that incorporates the following 3 elements: (1) There occurs a superposition of a topographic gradient of neuronal loss in brainstem and basal forebrain structures related to the disease process and an aging-related temporal gradient. (2) While PD is a chronic progressive disorder, the most important determinant of clinical progression is advancing age rather than disease duration. (3) The effects of the disease process and aging on nondopaminergic structures involve a biologic interaction. The model implies that understanding the degenerative process in nondopaminergic structures in PD as it relates to molecular mechanisms accompanying the aging of the nervous system may create opportunities for interventions affecting the clinical progression of the disease.

P2-245: White matter changes associated with dementia development in patients with subcortical ischemic white matter lesions: A diffusion tensor image study

Diffusion tensor MRI (DTI) is a new technique that may provide a better index of white matter damage in central nervous system. Both discrete lacunar infarcts and leukoaraiosis are important mechanisms in developing dementia in patients with subcortical ischemic vascular lesions. But the location and severity of white matter changes associated with development of dementia has not been established yet. We investigate the difference of location and severity of white matter damage in patients with subcortical ischemic vascular lesions with and without dementia. Eleven demented patients(age: 74.80 yrs, MMSE: 22.10) who fulfill the criteria of Erkinjuntti's subcortical ischemic vascular dementia (SIVD) criteria, ten patients (age: 67.50 yrs, MMSE: 26.63) with subcortical vascular cognitive impairment no dementia (SVCIND) and twelve healthy volunteers(age: 70.64 yrs, MMSE: 28.73) were recruited. They underwent DTI, neuropsychological assessment and clinical interview. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu, body and splenium), cingulate white matter(anterior and posterior), internal capsule(anterior and posterior limb), superior and inferior longitudinal fasciculus, centrum semiovale, hippocampus, and anterior thalamus. SVCIND and SIVD patients showed lower FA and higher MD values in the both frontal, occipital, right anterior thalamus, centrum semiovale, superior longitudinal fasciculus and in both hippocampi than the control group. Compared to SVCIND patients, SIVD patients had decreased FA values and increased MD values in both frontal areas and decreased MD in left superior longitudinal fasciculus. The findings support the white matter damage and disruption in the frontal region and superior association fiber is important for the cognitive dysfunctions associated with dementia development in patients with subcortical ischemic lesions. This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea(A050079).