Restricted ocular exploration does not seem to explain simultanagnosia

One major function of parietal cortex is to direct our attention towards salient stimuli. The present data suggest that it also plays an important role in visual gestalt perception. Patients with simultanagnosia following lesions in this area are not able to extract the meaning of a visual scene whereas being perfectly able to recognise individual objects of this scene. We tested two patients with simultanagnosia with hierarchical Navon figures combined with eye movements recordings. The patients' performance allowed us to compare directly the scan paths in trials in which the global letter shape was recognised with trials in which the global letter shape was not recognised. We did not find any obvious differences in the eye movement pattern related to the two perceptual situations. The two patients did not show a significant problem in shifting their eyes (and thus possibly also their attentional focus) to all aspects of the complex visual stimulus when attempting to bind together the different elements of spatially distributed information. The results demonstrate that restricted ocular exploration cannot be the reason for the patients' inability to recognise the global shape of stimuli. Our data rather suggest a role of parietal cortex in visual gestalt perception that is beyond its role of directing attention towards relevant objects.     

APOE epsilon4 does not predict mortality, cognitive decline, or dementia in the oldest old

OBJECTIVE: To examine the effect of the epsilon 4 allele on cognitive decline in the oldest old. METHODS: We studied all 601 citizens of the city of Vantaa age 85 years and older in 1991. A total of 553 subjects (92%) took part in the study, which used the Mini-Mental State Examination (MMSE) and assessment of dementia according to the Diagnostic and Statistical Manual of Mental Disorders, third ed., revised (DSM-III-R) criteria. The survivors were re-examined 3 years later. APOE genotype was determined in 510 subjects, representing 83.2% of the original population. RESULTS: Approximately one-half of the subjects (n = 250) died before the follow-up, and 253 subjects (97.3% of the survivors) were re-examined. The occurrence of the APOE epsilon 4 allele did not have any significant effect on survival. Of the 187 previously nondemented subjects, 58 (31%) had developed dementia. The OR for the epsilon 4 carriers to develop dementia was not significant: OR = 1.78; 95% CI = 0.88 to 3.60. In individuals with a follow-up MMSE score (n = 222), the mean decline in the score was 3.1 points. APOE epsilon 4 carrier status did not have a significant effect on the mean MMSE change except in the previously demented subjects, among whom the drop was larger in the APOE epsilon 4 carriers. CONCLUSIONS: The lack of association between APOE epsilon 4 carrier status and mortality, or development of dementia, or cognitive decline in these very elderly people, whether analyzed in the whole population or among the nondemented subjects only, suggests that the APOE epsilon 4 effect in younger subjects is age-dependent, and that it is no longer present in very old age.     

The overlap between neurodegenerative and vascular factors in the pathogenesis of dementia

There is increasing evidence that cerebrovascular dysfunction plays a role not only in vascular causes of cognitive impairment but also in Alzheimer’s disease (AD). Vascular risk factors and AD impair the structure and function of cerebral blood vessels and associated cells (neurovascular unit), effects mediated by vascular oxidative stress and inflammation. Injury to the neurovascular unit alters cerebral blood flow regulation, depletes vascular reserves, disrupts the blood–brain barrier, and reduces the brain’s repair potential, effects that amplify the brain dysfunction and damage exerted by incident ischemia and coexisting neurodegeneration. Clinical-pathological studies support the notion that vascular lesions aggravate the deleterious effects of AD pathology by reducing the threshold for cognitive impairment and accelerating the pace of the dementia. In the absence of mechanism-based approaches to counteract cognitive dysfunction, targeting vascular risk factors and improving cerebrovascular health offers the opportunity to mitigate the impact of one of the most disabling human afflictions.     

ATXN2 with intermediate-length CAG/CAA repeats does not seem to be a risk factor in hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) confines a group of heterogeneous neurodegenerative disorders characterized by progressive spasticity and lower limb weakness. Age of onset is highly variable even in familial cases with known mutations suggesting that the disease is modulated by other yet unknown parameters. Although progressive gait disturbances, lower limb spasticity and extensor plantar responses are hallmarks of HSP these characteristics are also found in other neurodegenerative disorders, e.g. amytrophic lateral sclerosis (ALS). HSP has been linked to ALS and frontotemporal degeneration with motor neuron disease (FTD-MND), since TDP-43 positive inclusions have recently been found in an HSP subtype, and TDP-43 are found in abundance in pathological inclusions of both ALS and FTD-MND. Furthermore, ataxin-2 (encoded by the gene ATXN2), a polyglutamine containing protein elongated in spinocerebellar ataxia type 2, has been shown to be a modulator of TDP-43 induced toxicity in ALS animal and cell models. Finally, it has been shown that ATXN2 with non-pathogenic intermediate-length CAG/CAA repeat elongations (encoding the polyglutamine tract) is a genetic risk factor of ALS. Considering the similarities in the disease phenotype and the neuropathological link between ALS and HSP we hypothesized that intermediate-length CAG/CAA repeats in ATXN2 could be a modulator of HSP. We show that in a cohort of 181 HSP patients 4.9 % of the patients had intermediate-length CAG/CAA repeats in ATXN2 which was not significantly different from the frequencies in a Danish control cohort or in American and European control populations. However, the mean age of onset was significantly lower in HSP patients with intermediate-length CAG/CAA repeats in ATXN2 compared to patients with normal length repeats. Based on these results we conclude that ATXN2 is most likely not a risk factor of HSP, whereas it might serve as a modulator of age of onset.     

The association between inconsistent handedness and psychopathy does not extend to the domain of moral reasoning

A recent study [Shobe, E., & Desimone, K. (2016). Inconsistent handers show higher psychopathy than consistent handers. Laterality: Asymmetries of Body, Brain and Cognition, 21(2), 143–160. doi:10.1080/1357650X.2015.1089879] found an association between inconsistent handedness (the use of one's non-dominant hand for some tasks) and psychopathy. Because this provides evidence for an association between an individual difference and a trait that is perceived negatively, the present study set out to (1) attempt to replicate the finding and (2) determine whether inconsistent handedness and psychopathy predict similar patterns of moral reasoning. An Mturk sample of 344 adults took the Edinburgh Handedness Inventory, the Short Dark Triad Questionnaire, and the Moral Foundations Questionnaire. The finding of a modest association between handedness and psychopathy was replicated. However, handedness and psychopathy predicted totally different response patterns on the Moral Foundations Questionnaire, with psychopathy predicting less concern for others and fairness and inconsistent handedness predicting less respect for authority and less in group loyalty.     

Lack of association between apolipoprotein E polymorphism and vascular dementia in Koreans

To investigate an association of vascular dementia (VD) with the apolipoprotein E (APOE) polymorphism, the APOE polymorphism of 100 VD patients, 100 age- and gender-matched Alzheimer disease (AD) patients, and 200 age- and gender-matched nondemented control (NC) subjects was genotyped. The distribution of APOE polymorphism was compared. Neither the APOE epsilon4 allele nor the APOE epsilon2 allele was more prevalent in the VD patients compared with the NC subjects (P > .1 by the chi 2 test), which was the case when both men and women were analyzed separately (P > .1 by the chi2 test) and when young patients (75 years old or less) and old patients (more than 75 years old) were analyzed separately (P > .1 by the chi2 test). The estimated statistical power was over 0.80 when the odds ratios (OR) for VD conferred to the APOE epsilon4 are assumed to be higher than 2.2 and the type I error probability is set at 0.05, which is much higher than the power of the previous studies on the VD/APOE association. In conclusion, the results suggested that APOE epsilon4 allele does not confer the risk for VD, and even if it does, it does so very modestly.     

Prospective Belgian study of neurodegenerative and vascular dementia: APOE genotype effects

OBJECTIVE: The authors conducted a prospective study of neurodegenerative and vascular dementia in Belgium. Strict diagnostic inclusion criteria were used to include well defined patients and controls. The results of apolipoprotein E (APOE) genotype effect on risk and clinical characteristics are presented. METHODS: APOE genotyping was performed in patients with probable Alzheimer's disease (AD) (n=504), frontotemporal dementia (FTD) (n=47), vascular dementia (VaD) (n=152), mixed dementia (n=132), mild cognitive impairment (MCI) (n=44), Parkinson's disease (PD) (n=30), dementia with Lewy bodies (DLB) (n=17), and multisystem atrophy (MSA)/progressive supranuclear palsy (PSP) (n=12). RESULTS: The APOE allele frequencies of this Belgian control population (epsilon 2: 6.9%; epsilon 3: 76.2%; epsilon 4: 16.9%) did not differ from those reported for other white populations. AD, MCI, and mixed dementia patients had higher APOE epsilon 4 (32.9%, 38.6%, and 28.4% respectively) and lower APOE epsilon 3 (62.2%, 53.4%, and 66.3%) frequencies compared with controls, whereas only AD and mixed dementia patients had lower APOE epsilon 2 frequencies (4.9% and 5.3%). Apart from a borderline significant different distribution of APOE allele frequencies in VaD patients compared with controls, no other differences were detected. The influence of APOE epsilon 4 on clinical features of dementia was limited to lower age at onset in AD patients and a less pronounced negative correlation between age at onset and number of epsilon 4 alleles in MCI and mixed dementia patients. CONCLUSIONS: This study confirmed the risk association between APOE epsilon 4 and AD. The observation that APOE epsilon 4 is associated with mixed dementia reflected the role of AD in the aetiopathogenesis of this condition. Although MCI is an aetiologically heterogeneous syndrome, the increased APOE epsilon 4 frequencies indicated that a large proportion of the MCI patients included in the study might be predisposed to develop AD.     

APOE genotype predicts AD and other dementia but not ischemic cerebrovascular disease

BACKGROUND: The APOE polymorphism is an important modulator of plasma lipoproteins and a risk factor for AD. The hypothesis that APOE genotype, through its effect on lipoproteins, is a common risk factor for ischemic cerebrovascular disease (ICVD), AD, and other dementia (OD) was tested. METHODS: The authors genotyped 9241 individuals from the general population, 452 patients with ICVD and > or = 50% stenosis of the carotid arteries, and 75 patients with ICVD before the age of 50 years. Among the individuals from the general population, 211 had ICVD, 26 had AD, and 28 had OD. RESULTS: The APOE polymorphism was not associated with ICVD in any of the three patient groups. In contrast, the epsilon43 and epsilon44 genotypes were associated with 3- and 10-fold risks of AD (95% CI = 1.4 to 8.0 and 2.5 to 41.0), and the epsilon43 genotype was also associated with a 2.5-fold risk of OD (95% CI = 1.1 to 5.5). These increases in risk were not abolished by adjustment for lipids and lipoproteins. The fraction of AD that could be attributed to the epsilon43 and epsilon44 genotypes was 37 and 20% in the general population, whereas the fraction of OD that could be attributed to the epsilon43 genotype was 26%. CONCLUSION: The APOE polymorphism is a risk factor for AD and OD independent of lipid and lipoprotein levels but does not affect the risk of ICVD.     

Neurally mediated syncope starting in old age does not appear to be unique to humans: new perspective

Clinical Autonomic Research -     

阿尔茨海默病和血管性痴呆的载脂蛋白E基因多态性研究

目的探讨载脂蛋白E(ApoE)基因与中国昆明地区汉族人阿尔茨海默病(AD)和血管性痴呆(VD)是否存在关联。方法运用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法对58例无亲缘关系的中国昆明地区AD患者、10例VD患者及96例健康老年人,进行ApoE基因变异检测,并进行统计分析。结果AD组、VD组ApoEε3/ε4基因型频率及ε4等位基因频率高于健康对照组,差异比较有统计学意义(P<0.05)。结论ε4基因可能是AD和VD的危险因素。     

中国人ApoE基因多态性与血管性痴呆关系的Meta分析

目的评价我国人群ApoE基因多态性与血管性痴呆的关系。方法对1996年1月至2011年5月公开发表的关于中国人血管性痴呆ApoE基因多态性的病例对照研究进行Meta分析。结果共纳入20个病例对照研究。Meta分析结果表明,中国人携带ε4等位基因的个体发生血管性痴呆的危险性的合并OR值为2.20[95%CI(1.81,2.66)];中国汉族人携带ε4等位基因的个体发生血管性痴呆的危险性的合并OR值为3.11[95%CI(2.06,4.69)]。结论载脂蛋白E基因多态性与中国人血管性痴呆相关,携带ε4等位基因的个体有发生血管性痴呆的倾向。     

The effect of APOE on dementia is not through atherosclerosis: the Rotterdam Study.

The APOE genotype is involved in atherosclerosis, and atherosclerosis increases the risk of dementia, in particular among carriers of the APOE-epsilon4 allele. We studied, in a population-based setting (244 dementia cases; 1,002 nondemented controls), whether APOE is associated with dementia through atherosclerosis. As neither adjusting nor stratification for atherosclerosis altered the association of APOE with dementia, our study suggests that atherosclerosis is not an intermediate factor.     

关注血管因素与痴呆

美国心脏病协会、美国卒中协会举办的2008国际卒中大会(ISC)于2008年2月19日～22日在路易斯安那州的新奥尔良市举行。本届会议就卒中的基础和临床进展、防治、康复等内容进行讨论。血管因素与痴呆是其中一个十分重要的内容。加拿大Western Ontario大学的Cechetto教授指出每3个人     

Lack of association between interleukin-1alpha polymorphism and Alzheimer disease or vascular dementia

Recently, a C/T polymorphism in the promoter region of the interleukin 1-alpha (IL-1alpha) gene (position -889) was reported to be associated with Alzheimer disease. In this study, the polymorphism of IL-1alpha was examined in patients with Alzheimer disease, vascular dementia, and nondemented controls in a Chinese population in Taiwan. No difference was found in the IL-1alpha T allele frequency among the three groups. The predominant polymorphic allele ( approximately 90%) of IL-1alpha was the C allele. The APOE4 allele was overrepresented in the AD cohort. The presence of the APOE4 allele did not influence the IL-1alpha genotype or allele distribution. The prevalence of the IL-1alpha T allele, in particular the homozygous form, was lower than in whites and may account for the lack of association between IL-1alpha C/T polymorphism and Alzheimer disease among Chinese in Taiwan. The presence of the heterozygous IL-1alpha T allele cannot be used for distinguishing Alzheimer disease or vascular dementia from controls.     

Hematologic risk factors of vascular disease and their relation to dementia

Multiple studies have implicated vascular-related conditions as risk factors for dementia. Clarification of these factors in dementia is important because most are modifiable, and may serve as the basis for preventive strategies. Several hematologic factors are associated with vascular diseases, but their relation to dementia is unclear. This review examines biological and epidemiological evidence concerning the role of these hematologic factors in dementia, and dementia subtypes. Reviewed factors include homocysteine, cholesterol, fatty acids, antioxidants, and C-reactive protein. The vast majority of studies reviewed are cross-sectional. Longitudinal studies with serial hematologic measures are needed to clarify the relationship between these factors and dementia over the lifespan. A necessary step is to examine multiple hematologic factors simultaneously, rather than in isolation, to determine how these factors are interrelated.     

The association between semantic dementia and surface dyslexia in Japanese

One theory about reading suggests that producing the correct pronunciations of written words, particularly less familiar words with an atypical spelling-sound relationship, relies in part on knowledge of the word's meaning. This hypothesis has been supported by reports of surface dyslexia in large case-series studies of English-speaking/reading patients with semantic dementia (SD), but would have increased credibility if it applied to other languages and writing systems as well. The hypothesis predicts that, of the two systems used to write Japanese, SD patients should be unimpaired at oral reading of kana because of its invariant relationship between orthography and phonology. By contrast, oral reading of kanji should be impaired in a graded fashion depending on the consistency characteristics of the kanji target words, with worst performance on words whose component characters take ‘minority’ (atypical) pronunciations, especially if the words are of lower frequency. Errors in kanji reading should primarily reflect assignment of more typical readings to the component characters in these atypical words. In the largest-ever-reported case series of Japanese patients with semantic dementia, we tested and confirmed this hypothesis.