Gender-specificities in Alzheimer's disease and mild cognitive impairment

Background Amnestic Mild Cognitive Impairment (MCI) is a condition with an increased risk for developing Alzheimer's disease (AD). Presently, gender differences are neglected in the assessment of MCI and AD. Methods We examined verbal and visuospatial episodic memory in 143 subjects diagnosed as healthy controls (HC; N = 48, Mini-Mental State Examination (MMSE) 29.2 ± 1.0 (mean ± standard deviation)), MCI (N = 43,MMSE 28.5 ± 1.4), and AD (N = 49, MMSE 25.1 ± 2.2). Findings Female HC and MCI subjects performed better on verbal episodic memory tasks than males. In contrast, visuospatial episodic memory was better in male than female AD patients. Conclusions We interpret the results in light of a genderspecific cognitive reserve and conclude that the gender-specificity of neuropsychological performance needs to be accounted for in clinical diagnosis of Alzheimer’s disease.     

Effectiveness of Traditional Chinese Medicine (TCM) treatments on the cognitive functioning of elderly persons with mild cognitive impairment associated with white matter lesions

Background

Cerebral white matter lesion (WML) is a pathological change of the white matter which is considered an early sign of brain impairment in elderly individuals, so it is reasonable to administer early dementia prevention programs to individuals with WML.Traditional Chinese Medicine (TCM) has developed several approaches to prevent or delay the onset of dementia that have, as yet, not been formally tested.

Aim

Evaluate the effects of a 6-month TCM intervention for elderly persons with mild cognitive impairment and WML.

Methods

Eighty individuals 65 years of age or older with radiological evidence of WML and mild cognitive impairment based on the Montreal Cognitive Assessment (MoCA) were classified into the four main TCM constitutional types (qi deficiency, yang deficiency, phlegm dampness, or blood stasis) and randomly assigned to a treatment group or a treatment-as-usual control group. The treatment group participated in training focused on diet, lifestyle, exercises, and emotional regulation adjustment; they also received six monthly courses of moxibustion (heating acupoints by burning the moxa of dried mugwort), each of which involved 10 daily 15-minute sessions focused on three targeted acupoints (one of which was specific to the constitutional type). Changes in the MoCA and in the score of each of the four constitutional types were the main outcomes assessed.

Results

Two participants dropped out of each group over the 6 months, leaving 38 in each group. Based on repeated measures analysis of variance, the total MoCA score, four of the six MoCA subscales scores (visual space and executive function, naming, attention and calculation, and delayed memory), and all four of the TCM constitution type scores showed significantly greater improvement over the 6 months in the treatment group than in the control group.

Conclusion

This study shows that TCM interventions can improve both the cognitive functioning and the severity of symptoms considered in the TCM assessment of constitutional types among elderly individuals with mild cognitive impairment and WML. Long-term follow-up studies that use blinded evaluation of the outcome are needed to determine whether or not constitution-specific TCM treatments can prevent the onset of dementia.     

脑白质病变与轻度认知功能障碍的关系

目的 探讨脑白质病变(WML)与轻度认知功能障碍(MCI)的关系.方法 71例WML患者根据头颅MRI检查分为轻度组(27例)、中度组(21例)、重度组(23例),39例无WML的对照者为对照组.对入组者进行神经心理学量表检查;比较各组MCI的患病率,分析WML与MCI的相关性.结果 WML轻、中、重度组的MCI患病率明显高于对照组(均P＜0.01);WML中、重度组简易精神状态检查(MMSE)及蒙特利尔认知评估量表(MoCA)评分显著低于WML轻度组和对照组(均P＜0.01);随着WML程度的加重,除了抽象能力评分,MoCA其他各认知领域的评分均显著降低(均P＜0.05).多元线性相关分析显示,WML程度与MMSE、MoCA总分及除抽象思维能力的各认知域评分呈负相关(r=-0.252 ～-0.782,均P＜0.01).结论 WML可导致MCI,其对认知功能障碍的影响与WML的程度有关.     

Non-pharmacological interventions for Parkinson's disease mild cognitive impairment: future directions for research

Parkinson’sdisease-mildcognitiveimpairment(PD-MCI)currently represents a valid diagnostic clinical entity with potential interest for therapeutic purpose.MCI is present in approximately 25–30%of non-demented patients with PD(Weintraub et al.,2018).Several risk factors are associated with Parkinson’s disease dementia(PDD)occurrence,such asoldageatonset,longdiseaseduration,motorimpairment and MCI(Nicoletti et al.,2019).     

Executive dysfunction and periventricular diffusion tensor changes in amnesic mild cognitive impairment and early Alzheimer's disease

Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimer's disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal‐related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

中国轻度认知功能损害的研究进展（英文）

中国人口的迅速老龄化促进了对老年痴呆及其前体(轻度认知功能损害,MCI)的病因和预防的研究。本文综述了过去十年中国有关MCI的研究。有关MCI的流行病学、神经心理特征、诊断学、遗传病因学、神经影像学和电生理变化以及治疗方面的广泛研究已提供了一些新的见解,但很少有突破结果。对于MCI的预防与治疗,未来的发展方向则更注重具有代表性的大样本多学科前瞻性研究,并使用标准化方法来评估和监测认知功能随着时间的推移而产生的变化。     

Regional white matter hyperintensities in normal aging, single domain amnestic mild cognitive impairment, and mild Alzheimer’s disease

Few studies have examined white matter hyperintensities (WMH) along the cognitive continuum between single-domain amnestic mild cognitive impairment (sd-aMCI) and Alzheimer’s disease (AD). The aims of our study were to explore relationships between the extent and location of WMH and disease severity along the cognitive continuum and to determine whether differences in the distribution of WMH could be predictive of specific patterns of cognitive impairment. We compared cognitive function, vascular risk factors, and regional (frontal lobe, parieto-occipital [PO] lobe, temporal lobe, periventricular [PV] white matter and deep white matter) WMH volume in 37 patients with mild AD, 23 patients with sd-aMCI, and 24 age-matched and education-matched normal controls. A quantitative volumetric method was applied to measure WMH burden. Total and regional WMH burdens, except for those in the temporal lobe, were significantly correlated with age (p < 0.01). We found a trend toward increasing WMH volume with disease severity, higher in AD than in sd-aMCI and lowest in the controls. Total WMH volume was associated with the global cognitive test score. In multiple linear regression analysis, PV WMH volume, but not deep WMH volume, strongly predicted performances on the Controlled Oral Word Association test and the Color Word Stroop test after adjusting for important demographic variables. Only PO WMH volume was a significant predictor of a cognitive test score when frontal and temporal WMH volumes were simultaneously entered into the regression model. The extent and distribution of WMH, especially in the PV and PO regions, were associated with disease severity and reduced cognition.     

Differences in grey and white matter atrophy in amnestic mild cognitive impairment and mild Alzheimer's disease

Background:  Grey matter (GM) atrophy has been demonstrated in amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD), but the role of white matter (WM) atrophy has not been well characterized. Despite these findings, the validity of aMCI concept as prodromal AD has been questioned.
Methods:  We performed brain MRI with voxel-based morphometry analysis in 48 subjects, aiming to evaluate the patterns of GM and WM atrophy amongst mild AD, aMCI and age-matched normal controls.
Results:  Amnestic mild cognitive impairment GM atrophy was similarly distributed but less intense than that of mild AD group, mainly in thalami and parahippocampal gyri. There were no difference between aMCI and controls concerning WM atrophy. In the mild AD group, we found WM atrophy in periventricular areas, corpus callosum and WM adjacent to associative cortices.
Discussion:  We demonstrated that aMCI might be considered a valid concept to detect very early AD pathology, since we found a close proximity in the pattern of atrophy. Also, we showed the involvement of WM in mild AD, but not in aMCI, suggesting a combination of Wallerian degeneration and microvascular ischaemic disease as a plausible additional pathological mechanism for the discrimination between MCI and AD.     

A rat model of mild cognitive impairment associated with vascular factor

Vascular factors have been shown to be important in cognitive impairment and dementia in the elderly. Recent evidence suggests that treatment at the stage of mild cognitive impairment (MCI) can prevent progression to dementia. In this study we established a rat model that simulates the pathophysiological condition of vascular MCI, characterized by gait disturbance in the absence of motor deficits and mild working memory dysfunction and not being demented. Initiation of vascular MCI pathology was not associated with loss of neurons, but was correlated with microglial activation and white matter changes. This MCI rat model will be useful for analysis of effects of vascular factors on cognitive dysfunction and neurodegenerative processes and development of drugs for treatment of this disorder.     

White matter vascular lesions are related to parietal-to-frontal coupling of EEG rhythms in mild cognitive impairment

Do cerebrovascular and Alzheimer's disease (AD) lesions represent additive factors in the development of mild cognitive impairment (MCI) as a putative preclinical stage of AD? Here we tested the hypothesis that directionality of fronto‐parietal functional coupling of electroencephalographic (EEG) rhythms is relatively preserved in amnesic MCI subjects in whom the cognitive decline is mainly explained by white‐matter vascular load. Resting EEG was recorded in 40 healthy elderly (Nold) and 78 amnesic MCI. In the MCI subjects, white‐matter vascular load was quantified based on magnetic resonance images (0–30 visual rating scale). EEG rhythms of interest were δ (2–4 Hz), θ (4–8 Hz), α1 (8–10.5 Hz), α2 (10.5–13 Hz), β1 (13–20 Hz), and β2 (20–30 Hz). Directionality of fronto‐parietal functional coupling of EEG rhythms was estimated by directed transfer function software. As main results, (i) fronto‐parietal functional coupling of EEG rhythms was higher in magnitude in the Nold than in the MCI subjects; (ii) more interestingly, that coupling was higher at θ, α1, α2, and β1 in MCI V+ (high vascular load; N = 42; MMSE = 26) than in MCI V? group (low vascular load; N = 36; MMSE= 26.7). These results are interpreted as supporting the additive model according to which MCI state would result from the combination of cerebrovascular and neurodegenerative lesions. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.     

DemTect: a new, sensitive cognitive screening test to support the diagnosis of mild cognitive impairment and early dementia

OBJECTIVES: To design a new, highly sensitive psychometric screening to identify patients with mild cognitive impairment (MCI) and patients with dementia in the early stages of the disease. METHODS: Five tasks were included in the DemTect: a word list, a number transcoding task, a word fluency task, digit span reverse, and delayed recall of the word list. The normation was performed with 145 healthy control subjects (CG). Furthermore, 97 MCI patients and 121 patients with possible Alzheimer's disease (AD) were tested with the DemTect and the MMSE. Classification rates for both tests were analysed. RESULTS: On the basis of the CG data, age-dependant transformation algorithms for the DemTect subtests were defined, and an education correction was provided for the total transformed score. The patient groups scored significantly below the CG in both the DemTect and the MMSE. Compared to the MMSE, classification rates of the DemTect were superior for both the MCI and the AD group, with high sensitivities of 80% and 100%, respectively. CONCLUSIONS: The DemTect is short (8-10 minutes), easy to administer, and its transformed total score (maximum 18) is independent of age and education. The DemTect helps in deciding whether cognitive performance is adequate for age (13-18 points), or whether MCI (9-12 points) or dementia (8 points or below) should be suspected.