Increased saliva cortisol awakening response in patients with mild cognitive impairment

BACKGROUND: It is unknown whether HPA-axis dysfunction is present in patients with mild cognitive impairment (MCI). The aim of the present study was to investigate whether cortisol levels are elevated among patients with MCI and/or whether the individuals have adequate feedback control of their HPA axis. MATERIAL AND METHODS: 27 patients with MCI and 15 healthy controls were included in the study. Saliva samplings were performed 5 times a day before intake of 0.5 mg dexamethasone, and 5 times a day after intake of dexamethasone, respectively. RESULTS: Significantly higher cortisol levels were found 15 min after awakening among patients with MCI in comparison with the controls, both before and after dexamethasone administration (p<0.05). Also, the ratio between cortisol at awakening time and 15 min after awakening was lower in the patient group after dexamethasone administration (p<0.05). There were no significant differences in basal cortisol levels before or after dexamethasone between groups. CONCLUSION: The results indicate that there is an HPA-axis disturbance, with normal basal cortisol levels and increased awakening response among patients with MCI. The dissociation between basal values and the awakening response may be of pathophysiological importance for the cognitive impairment.     

老年人轻度认知功能损害的神经心理测验研究

目的;用神经心理测验研究老年人轻度认知功能损害的特点。方法;为横断面比较研究。研究对象分为两组,即有轻度认知功能损害的老年人（ＭＣＩ组）和认知功能正常的老年人（对照组,ＮＣ组）。以世界卫生组织老年认知功能介成套神经心理测验（ＷＨＯ－ＢＣＡＩ）为主要研究工具。     

Medication reminder device for the elderly patients with mild cognitive impairment

Reminder devices reportedly improve medication adherence in the elderly patients with mild dementia; however, the efficacy of such devices remains unexplored. Therefore, a 3-month before and after study with convenience sampling was conducted to determine the efficacy of a medication reminder device used by 18 participants (aged 81.2 ± 6.2 years) with Clinical Dementia Rating scores of 0.5 or 1. At the onset of device use, examiners visited the users' homes to ensure that they and their caregivers understood how to use the device. Caregivers monitored its use during the first week. Values of the self-administration medication rate during 1 week for 13 (72.2%) users showed improvement at 3 months. This result revealed that reminder devices can improve medication adherence in the elderly patients with mild cognitive impairment. Further study is needed to assess the magnitude of this improvement and to enhance its support for users with mild cognitive impairment.     

Physical activity and executive functions in the elderly with mild cognitive impairment

The primary goal of the present study was to examine whether in the elderly with mild cognitive impairment (MCI), the effect of physical activity measured directly following treatment, was reflected in an improvement in cognitive functioning in general or in executive functions (EF) in particular. Secondly, this study aimed to compare the effectiveness of two types of intervention, with varying intensities: walking and hand/face exercises. Forty-three frail, advanced elderly subjects (mean age: 86) with MCI were randomly divided into three groups, namely, a walking group (n=15), a group performing hand and face exercises (n=13), and a control group (n=15). All subjects received individual treatment for 30 minutes a day, three times a week, for a period of six weeks. A neuropsychological test battery, administered directly after cessation of treatment, assessed cognitive functioning. The results show that although a (nearly) significant improvement in tasks appealing to EF was observed in both the walking group and the hand/face group compared to the control group, the results should be interpreted with caution. Firm conclusions about the effectiveness of mild physical activity on EF in the oldest old can only be drawn after studies with larger number of subjects.     

Cholinotrophic molecular substrates of mild cognitive impairment in the elderly

Cholinergic nucleus basalis (NB) neurons provide the major cholinergic innervation to the cortical mantle, are selectively vulnerable in late stage Alzheimer's disease (AD) and require the neurotrophin, nerve growth factor (NGF) and its receptors (TrkA and p75(NTR)), for their survival. The molecular events underlying the demise of these neurons in AD were investigated using tissue harvested from participants in a longitudinal clinical pathological study of aging and AD who agreed to an annual clinical evaluation providing a categorization of no cognitive impairment (NCI), mild cognitive impairment (MCI) or AD and postmortem brain donation. Although the number of choline acetyltransferase (ChAT)-positive neurons was unchanged, TrkA and p75(NTR) receptor-containing neurons, which co-localize with ChAT, were significantly reduced in the NB of subjects with MCI and AD compared to those with NCI. These observations indicate a phenotypic down-regulation rather than frank NB neuronal degeneration in MCI. Expression profiling of single cholinergic NB neurons revealed TrkA but not p75(NTR) mRNA is reduced in MCI, suggesting that decreased neurotrophin responsiveness may be an early biomarker for AD. The NGF precursor molecule, proNGF, is increased in the cortex in MCI and AD. Since proNGF accumulates in the presence of reduced cortical TrkA and sustained levels of p75(NTR), a shift in the balance between cell survival and death molecules may occur in prodromal AD. Coincident with these phenomena, brain derived neurotrophic factor (BDNF) and its precursor molecule, proBDNF, are reduced in the MCI cortex, potentially depriving CBF neurons of additional trophic factor support. Moreover, there is a shift in the ratio of 3 repeat tau to 4 repeat tau gene expression, whereas total tau message is stable in NB neurons during the disease process. These data suggest there is a shift in cholinotrophic molecular events in MCI and early AD which may lead to cell dysfunction and eventual cell death over the course of the disease. These findings support the concept that from a neurotrophic pathobiologic perspective, MCI is already early AD.     

离退休老人轻度认知功能损害研究

目的：探讨离退休老人轻度认知功能损害(MCI)的发生率及其影响因素。方法：采用哈金斯基缺血指数(HIS)、简易智能状态检查(中文版)(MMSE)、Reisberg总体衰退量表(GDS)、日常生活活动能力(20项版本)(ADL)等，对420名离退休老人MCI的发生情况及其影响因素进行调查，分析相互问关系。结果：离退休老人中MCI的发生率为8．6％，随年龄的增长而有升高趋势，但各年龄组之间差异无显著性。结论：离退休老人中MCI较常见，应对老年人群进行MCI的监测和干预，阻止和延缓MCI发展为痴呆，提高老年人的寿命和生活质量。     

老年遗忘型轻度认知损害患者语言工作记忆损害特点

目的 探讨老年遗忘型轻度认知损害(aMCI)患者语言工作记忆损害的特点及机制.方法 采用语言工作记忆检查软件对30例老年aMCI患者进行视觉语言工作记忆及词语流畅性和数字广度测试等神经心理学检查,并选择30名健康老人作对照.结果 aMCI患者的视觉语义工作记忆测试成绩正确率低于对照组,差异具有统计学意义(79.83%±3.22%与87.00%±1.93%,t=-1.03,P=0.002);视觉语音工作记忆测试成绩也低于对照组,但差异无统计学意义(78.92%±8.60%与86.80%±2.14%,t=-2.34,P=0.060);逆序数字广度测试(1.53±0.86与3.63±0.56,t=-1.23,P=0.027)和词语流畅性测试分值均低于对照组(22.96±2.31与31.53±3.72,t=-1.08,P=0.004),差异具有统计学意义.结论 老年aMCI患者的视觉语义性语言工作记忆受损,语音性语言工作记忆相对保留;逆序数字广度和词语流畅性测试成绩亦显著降低.     

Biomarker profiles and their relation to clinical variables in mild cognitive impairment

The aim of the study was to compare clinical variables between MCI patients at different risk for Alzheimer’s disease (AD) according to their biomarker profile. Fifty-four percent out of 39 MCI patients had a low Aβ42 and high tau in cerebrospinal fluid (CSF) (high-risk), 26% either a low CSF Aβ42 or high CSF tau (intermediate-risk) and 20% a normal CSF Aβ42 and tau (low-risk). Both high- and intermediate-risk subjects differed from the low-risk group in episodic memory, executive functions and the preclinical AD scale (PAS), which combines a set of clinical parameters. Subjects at high risk did not differ from subjects with an intermediate risk. Aβ42 levels correlated with the MTA and PAS scores, tau levels with episodic memory. These correlations suggest that the biomarkers are not independent when compared to the other AD markers. Longitudinal studies are necessary to interpret the correlations between biomarkers, imaging, and neuropsychological markers.     

Biomarker profiles and their relation to clinical variables in mild cognitive impairment

The aim of the study was to compare clinical variables between MCI patients at different risk for Alzheimer's disease (AD) according to their biomarker profile. Fifty-four percent out of 39 MCI patients had a low Abeta42 and high tau in cerebrospinal fluid (CSF) (high-risk), 26% either a low CSF Abeta32 or high CSF tau (intermediate-risk) and 20% a normal CSF Abeta42 and tau (low-risk). Both high-and intermediate-risk subjects differed from the low-risk group in episodic memory, executive functions and the preclinical AD scale (PAS),which combines a set of clinical parameters. Subjects at high risk did not differ from subjects with an intermediate risk. Abeta42 levels correlated with the MTA and PAS scores, tau levels with episodic memory. These correlations suggest that the biomarkers are not independent when compared to the other AD markers. Longitudinal studies are necessary to interpret the correlations between biomarkers, imaging, and neuropsychological markers.     

Frontotemporal mild cognitive impairment

Mild Cognitive Impairment appears to be a heterogeneous clinical entity comprising patients in the initial phases of distinct neurological disorders. Since frontotemporal dementia (FTD) is a relatively common neurodegenerative disease with an insidious onset, it might be possible to detect the patients in the initial phases of the disorder, before being demented. In the present work we proposed a set of criteria to identify patients with mild cognitive impairment of the frontotemporal type (FT-MCI), applied these criteria retrospectively to a large patient database, and evaluated the progression of the patients. Seven subjects fulfilling the proposed criteria for frontotemporal MCI were identified. They had symptoms of apathy, disinhibition, irritability and aggressiveness, untidiness, difficulties in decision making, obsessions and lack of concern for the others, for 1.5 +/- 0.8 years before the diagnosis of FT-MCI. Brain CT or MRI scan displayed fronto-temporal atrophy in five. Neuropsychological examination revealed deficits in tests dependent upon the frontal lobe, namely attention, verbal, motor and graphomotor initiatives and conceptual thinking. The patients kept their professional and daily activities, and were not demented. It was possible to have the follow-up of all patients. All but one patient diagnosed FT-MCI developed dementia of the frontotemporal type within 1.8 +/- 1.0 years. Application of the proposed criteria for FT-MCI, at least in this clinical neurological setting, can identify a group of patients with a high probability of further cognitive decline to dementia of the frontotemporal type.     

Cognitive profiles in Alzheimer's disease and in mild cognitive impairment of different etiologies

There has been increasing interest in determining whether amnestic, nonamnestic and multiple-domain subtypes of mild cognitive impairment (MCI) reflect different disease etiologies. In this study, we examined the extent to which cognitive profiles of nondemented patients with MCI diagnosed with prodromal Alzheimer's disease (AD) differed from those MCI patients diagnosed with vascular disease. We also compared these diagnostic groups to mildly demented patients diagnosed with AD and normal elderly controls. Results indicate that a majority of both MCI-AD and MCI-vascular patients experienced amnestic features and that multiple-domain was the most common presentation. MCI-AD and MCI-vascular groups did not differ on neuropsychological measures tapping memory, language, visuospatial skills/praxis or executive function. Further both MCI groups could be distinguished from dementia patients with regards to performance on measures of memory but not on non-memory measures. Considerable variability was observed in the degree of memory impairment among MCI patients with scores as much as 6 standard deviations below expected mean values. MCI-AD and MCI-vascular patients frequently exhibit both common and overlapping amnestic and nonamnestic features. The implication of these findings for future clinical research is discussed.