Does cerebral small vessel disease predict future decline of cognitive function in elderly people with type 2 diabetes?

Aims

We conducted a 3-year longitudinal study concerning an association between cognitive function and cerebral small vessel disease (SVD) seen on magnetic resonance imaging (MRI) in elderly type 2 diabetic patients.

Methods

Four cognitive function tests - MMSE, word recall, Digit Symbol Substitution (DSS), and Stroop Color Word (Stroop) - were performed in 67 diabetic patients twice in 2006 and 2009. SVD was diagnosed as silent brain infarct (SBI) and white matter lesions (WMLs) according to MRI.

Results

Number of SBI was significantly correlated with a decline in DSS and Stroop tests, while WMLs grade was only associated with it in DSS tests after adjustment for age, gender, education years, the presence of hypertension and dyslipidemia, and smoking. Severity of SVD at baseline was stronger associated with cognitive function after the 3-year follow-up than at baseline. WMLs progression was associated with more rapid decline of DSS tests compared to a group without progression.

Conclusions

SVD seen on MRI is a good marker for predicting future cognitive decline, and monitoring of treatment through the use of such markers is expected to maintain a good quality of life for elderly diabetic patients.     

Subject Index to Volume 25

We assessed whether subitem scores on the Mini-Mental State Examination (MMSE) associated independently with cerebral white matter hyperintensity (WMH) and lacunar infarction (LI). Magnetic resonance imaging (MRI) and neuropsychological evaluation (MMSE) were performed in 1008 elderly individuals from the Ohasama Study (348 men, 660 women [65.5%]; age 68.0 ± 6.0 [mean ± SD] years; MMSE score, 26.5 ± 2.9). The relationships between MRI findings and MMSE subitem scores were analyzed by logistic regression. Significant associations were observed between the MMSE subitems “Orientation to place” and WMH, and “Copy a figure” and LI. Pathological changes were detected by brain MRI associated with a decrease in cognitive function in healthy elderly individuals.     

White matter hyperintensities are an independent predictor of physical decline in community-dwelling older people

Background: Ageing is associated with physical disability, but little is known about the influence of white matter hyperintensities (WMHs) on physical function decline in older people. Objective: To investigate the role of WMHs as a predictor of decline in physical function in cognitively intact older people. Methods: 287 community-dwelling people aged 70-90 years underwent the Physiological Profile Assessment (PPA) and assessments of total and regional WMH volumes, cognitive function and comorbidities. Participants underwent reassessment of the PPA 12 months later, and those in the top quartile for increases in PPA scores over the year were regarded as having declined physically. Results: Multivariate logistic regression analyses revealed that people with WMH volumes in the 4th quartile showed greater physical decline (odds ratio 3.02, 95% confidence interval 1.02-8.95) while controlling for age, baseline physical function, general health, physical activity and cognitive function. Subsequent univariate analyses indicated that WMHs in the deep fronto-parietal and periventricular parieto-occipital regions had the strongest associations with physical decline. Conclusions: These findings indicate that WMHs are an independent predictor of decline in physical function and suggest that interventions that focus on preventing the development or progression of white matter lesions may help preserve physical function in older people.     

The effect of anemia and white matter hyperintensities (WMH) on cognitive impairment in patients with amnestic mild cognitive impairment (MCI)

Anemia and subcortical ischemic change might be associated with increased risks for cognitive impairment among the elderly. This study examined the associations among anemia, WMH and cognitive function in patients with amnestic MCI. We recruited 278 subjects with amnestic MCI from the Clinical Research Center for Dementia of South Korea (CREDOS), a hospital-based cohort study. A standardized neuropsychological battery, containing tests of language, visuospatial function, verbal memory and executive function, was used for all patients. Anemia was defined as a hemoglobin concentration below 12 g/dl for women and below 13 g/dl for men. The severity of WMH was also examined using brain magnetic resonance imaging (MRI). After multivariable adjustments, anemia and WMH were associated with poorer performance on cognitive function tests (anemia: Stroop test, F=4.17, p=0.042; WMH: Stroop test, F=6.45, p=0.002; Rey-complex figure test-copy, F=4.08, p=0.018). Moreover, a significant interaction between anemia and the severity of WMH was observed in performance on the Go/no go test (F=4.50, p=0.012) and the Stroop test (F=3.36, p=0.037). In post hoc analysis, anemic patients with severe WMH had significantly worse scores on measure of executive function (Go/no go test, p=0.011; Stroop test, p=0.001). Anemia and WMH had interactive effects on executive function impairment among the elderly with amnestic MCI.     

皮质下缺血性脑血管病的临床表现及磁共振特征与认知损害的关系

目的 分析皮质下缺血性脑血管病(SIVD)患者的临床特征、认知功能和磁共振成像特征,探讨SIVD患者腔隙性腩梗死(LI)和缺血性脑白质病变与认知损害的关系. 方法 依据Erkinjuntti提出的磁共振影像学(MRI)诊断标准确定SIVD患者53例,记录患者症状和体征,并进行神经心理学评估并行头部扫描.应用半自动MRI定量方法 测定其缺血性脑白质高信号(WMH)体积,记录LI数量,分析LI数量和缺血性脑白质病变与认知损害的关系. 结果 53例SIVD患者以假球麻痹症状和上运动神经元损伤体征最为常见,分别为18.9%(10/53)和37.7%(20/53).相关分析显示,年龄与WMH体积呈正相关(r=0.518,P<0.05),简易智能量表(MMSE)得分与wMH体积呈负相关(r=-0.514,P<0.05),控制其他混杂因素影响后,仅年龄与WMH体积呈正相关(r=0.400,P=0.004).控制年龄、性别和受教育时间影响因素前后,LI数量和WMH体积均与MMSE得分呈负相关(分别为r=-0.456,-0.514,-0.385,-0.382;均P<0.05).受教育时间与MMSE得分相关性具有统计学意义(r=0.518,P<0.001). 结论 年龄可能不是SIVD患者认知损害的主要危险因素.LI数量和缺血性脑白质病变均为SIVD认知功能损害的独立危险因素,LI数量增加、缺血性脑白质病变程度加重预示认知功能损害的恶化.     

Effect of renal impairment on cognitive function during a 3‐year follow up in elderly patients with type 2 diabetes: Association with microinflammation

Aims/Introduction

We investigated the effect of renal impairment on cognitive function during a 3‐year follow up in elderly type 2 diabetic patients, and an association with microinflammation.

Materials and Methods

Four cognitive function tests – Mini‐Mental State Examination (MMSE), word recall, Digit Symbol Substitution (DSS) and Stroop Color Word – were carried out in 67 patients. Renal impairment was defined as the presence of albuminuria and a decline in estimated glomerular filtration (eGFR) <60 mL/min/1.73 m². Inflammatory markers, such as highly sensitive C‐reactive protein (hs‐CRP), tumor necrotizing factor‐α (TNF‐α), interleukin (IL)‐1β and IL‐6, were measured at baseline.

Results

At baseline, cognitive decline was found in patients with renal impairment. The DSS test was independently associated with eGFR decline, whereas MMSE tended to be associated with albuminuria after adjusting for confounding factors. Regarding changes in cognitive function and renal impairment, changes in urinary albumin to creatinine ratios were strongly and independently associated with changes in word recall scores. In patients with persistent eGFR decline, there was a tendency toward a greater decrease in MMSE and DSS scores, whereas in those with newly detected albuminuria, there was a tendency toward a greater decrease in word recall scores. Increased baseline levels of hs‐CRP, TNF‐α and IL‐6 were associated with renal impairment and cognitive function, especially DSS tests, respectively. However, the increased levels were not independent predictors for cognitive decline.

Conclusions

The present study showed a reciprocal relationship between cognitive decline and renal impairment, especially progression of albuminuria. Thus, monitoring treatment using renal biomarkers will be important for preserving both renal and cognitive function.     

Blood pressure,executive function,and network connectivity in middle-aged adults at risk of dementia in late life

Midlife blood pressure is associated with structural brain changes, cognitive decline, and dementia in late life. However, the relationship between early adulthood blood pressure exposure, brain structure and function, and cognitive performance in midlife is not known. A better understanding of these relationships in the preclinical stage may advance our mechanistic understanding of vascular contributions to late-life cognitive decline and dementia and may provide early therapeutic targets. To identify resting-state functional connectivity of executive control networks (ECNs), a group independent components analysis was performed of functional MRI scans of 600 individuals from the Coronary Artery Risk Development in Young Adults longitudinal cohort study, with cumulative systolic blood pressure (cSBP) measured at nine visits over the preceding 30 y. Dual regression analysis investigated performance-related connectivity of ECNs in 578 individuals (mean age 55.5 ± 3.6 y, 323 female, 243 Black) with data from the Stroop color–word task of executive function. Greater connectivity of a left ECN to the bilateral anterior gyrus rectus, right posterior orbitofrontal cortex, and nucleus accumbens was associated with better executive control performance on the Stroop. Mediation analyses showed that while the relationship between cSBP and Stroop performance was mediated by white matter hyperintensities (WMH), resting-state connectivity of the ECN mediated the relationship between WMH and executive function. Increased connectivity of the left ECN to regions involved in reward processing appears to compensate for the deleterious effects of WMH on executive function in individuals across the burden of cumulative systolic blood pressure exposure in midlife.

Vascular risk factors (VRF) such as hypertension in midlife are associated with cognitive decline in late life (1–4). Notably, deficits in executive function, such as cognitive flexibility or inhibitory control, are early and “prominent” in vascular-related neurocognitive disorders (5). VRF are also associated with structural MRI brain changes such as white matter hyperintensities (WMH) (6), gray matter atrophy (7), and subcortical morphological changes (8), which may not be reversible. However, functional MRI (fMRI) changes may be detectable prior to irreversible structural damage. fMRI studies have shown that VRF are associated with reduced functional connectivity of brain networks and that this reduced network connectivity is associated with cognitive decline (9, 10). Understanding these relationships in midlife individuals and prior to the clinical onset of cognitive decline could provide significant insight into imaging markers that may identify individuals at risk of cognitive impairment and mechanisms for targeted interventions.In this study, we examined the relationship between blood pressure (BP), executive performance, and resting-state fMRI (rsfMRI) connectivity in participants from the brain substudy of the Coronary Artery Disease in Young Adults (CARDIA) longitudinal cohort study. We hypothesized that greater rsfMRI connectivity of executive control networks (ECN) would be related to better performance in an out-of-scanner executive control (Stroop) task. We further hypothesized that while the previously established relationship of systolic BP (SBP) to Stroop performance (11) would be mediated by WMH, the established relationship between WMH and executive function (12, 13) would be mediated by ECN connectivity.     

Cognitive function in Japanese elderly with type 2 diabetes mellitus

The current study was conducted to investigate the cognitive function in Japanese elderly with type 2 diabetes mellitus (DM). Participants included 69 diabetic and 27 nondiabetic subjects (60 to 85 years old). The cognitive functional tests conducted were the Mini-Mental State Examination (MMSE), Word Lists Recall (immediate, delayed), Digit Symbol Test (Wechsler Adult Intelligence Scale-Revised [WAIS-R]), and the Stroop Color Word Test. Hemoglobin A1c (HbA1c) was measured as the index of glycemic control, and information about recent hypoglycemic episodes was gathered by using questionnaires. Student's t test showed that DM subjects had significantly lower scores in the MMSE (P<.01) and Digit Symbol Test (P<.05) than non-DM subjects. The scores of the Digit Symbol Test in diabetes subjects had a significant negative relationship with HbA1c (r=-.433; P<.001), and insulin-use had a significant relationship with the scores of the MMSE and Digit Symbol Test. Subjects in the DM group were further divided by insulin use. Comparison of insulin-treated DM subjects, non-insulin-treated DM subjects, and nondiabetic subjects by analysis of variance followed by Bonferroni's post hoc test showed that insulin-treated DM subjects had significantly lower scores in the MMSE and Digit Symbol Tests than both non-insulin-treated DM subjects (P<.05) and nondiabetic subjects (P<.01). Our study suggests that Japanese elderly DM subjects, especially those with insulin treatment, have poor cognitive function.     

A six year follow-up study on the influence of silent ischemic brain lesions on cognitive function and brain atrophy in elderly people

METHODS: To investigate the influence of silent ischemic brain lesions (silent brain infarction (SBI) and periventricular hyperintensity (PVH) on cognitive function and brain atrophy, we studied MRI and cognitive tests in 27 healthy elderly people (above 65 years old) for 6 years. We examined Okabe's Scale for verbal intelligence, Koh's Block Design Test for performance intelligence and Zung's Self-rating Depression Scale (SDS). On MRI, lesions with high intensity on T2-weighted image and low intensity on T1-weighted image, and which were larger than 3 mm were diagnosed as SBI. The PVH was classified into 5 grades (0-4), and we divided the subjects into the PVH 0-1 group and the PVH 2-4 group. We evaluated brain atrophy using the ventricular area index (VAI) (the ratio of ventricular area to intracranial area at the level of lateral ventricle) on MRI by NIH image 1.55 (Macintosh). RESULTS: The SBI group and the PVH 2-4 group showed significant decline in Okabe's Score, and Koh's IQ, increase in SDS and VAI during six years. On the other hand, the non-SBI and the PVH 0-1 group showed a decline only in Okabe's score, and an increase in VAI. The rate of change in VAI was significantly higher in the subjects with SBI than those without it. However, there was no significant difference in the VAI change rate between the PVH 2-4 group and the PVH 0-1 group. CONCLUSION: Silent ischemic brain lesions such as SBI and PVH may have significant influence on decline of cognitive functions and progression of brain atrophy even in healthy elderly people.     

The brain reserve hypothesis, brain atrophy and aging

BACKGROUND: Researchers have used the concept of brain reserve to explain the dissociation between pathological brain damage and cognitive and functional performance. A variety of brain reserve hypotheses exist, and different empirical strategies have been employed to investigate these variants. OBJECTIVE: The study investigates (i) the relationship between measures of brain burden (atrophy, white matter hyperintensities (WMH)) and measures of reserve (education, creativity, and intelligence); (ii) the relationship between cognitive decline and reserve; (iii) whether measures of reserve mediate the effect of atrophy on estimated cognitive change, and (iv) the association between brain risk factors, education and atrophy. METHODS: A cross-sectional study of a sample of 446 individuals 60-64 years of age who underwent MRI scans as part of a large epidemiological study. Measures were taken of education, intelligence, creativity, cognitive speed, brain volume, WMH, estimated cognitive decline from earlier in life and brain atrophy. RESULTS: No association was found between estimated cognitive decline and brain burden (atrophy, WMH). Risk factors for brain insult were not associated with greater brain atrophy in the less well educated. Neither education, nor any other measure including intelligence or creativity, provided a buffer for cognitive decline in individuals with high levels of brain atrophy. CONCLUSION: Little support was found for the brain reserve hypothesis.     

A neuroradiological study on the influence of cerebral atrophy and white matter lesion on cognitive function in the elderly

We investigated the influence of brain atrophy and white matter lesions on cognitive function in elderly people. We selected 33 subjects (mean age, 79.2 +/- 5.1yrs) with a MMSE score from 14 to 30 who had no previous history of stroke from the outpatients in the Memory Clinic of our hospital. These subjects were divided into four groups on the basis of their MMSE score as follows: 14-20; moderate dementia (Moderate-D, n = 9), 21-23; mild dementia (Mild-D, n = 9), 24-27; mild cognitive impairment (MCI, n = 10), 28-30; normal (Normal, n = 5). Among these four groups, we compared the frequency of the associated risk factors for cerebral infarction (hypertension, diabetes mellitus, hyperlipidemia, heart disease), and the severity of brain atrophy and cerebral white matter lesion which were visually evaluated by MRI technique. Brain atrophy and white matter lesions were assessed by reviewing the cerebral cortex and hippocampus, and deep white matter lesion (DWML) and periventricular hyperintensity (PVH), respectively. Brain atrophy was divided into three grades (mild, moderate, severe) and white matter lesions were classified into four grades (0-3) using Fazekas's criteria. We performed statistical analysis to detect t parameters which correlate with and influence MMSE scores from among the MRI findings. The cases with dementia were all diagnosed as Alzheimer's disease. There were no significant differences among the four groups in mean age, the incidence of individual associated risk factors, the severity of cortical atrophy, or the grade of DWML (< or = 2) and PVH (< or = 2). However, the frequency of hippocampal atrophic change greater than a moderate grade increased in parallel with the exacerbation of reduced cognitive function (Normal; 20%, MCI: 40%, Mild-D; 56%, Moderate-D 89%), and approximately 76% with such a change were AD cases. Statistical analysis showed a significant negative correlation between the grade of hippocampal atrophy and MMSE score (r = -0.518, p < 0.005) and a great influence of hippocampal atrophy on that score (step-wise regression analysis: r = 0.518, p < 0.005). From the above results, it was suggested that more than moderate atrophic change in the hippocampus might possibly be related with cognitive impairment and that both DWML and PVH less than the second grade had little influence on the decline of brain function.     

Association between insulin resistance and cognitive function in elderly diabetic patients

Background:   Recently, cognitive impairment in elder diabetic subjects has sparked considerable interest. Insulin resistance (IR) is one of the central pathologies in diabetes mellitus, and several studies have shown that IR is associated with cognitive impairment in non-diabetic elderly subjects. However, the involvement of IR in cognitive dysfunction in the diabetic elderly has remained to be elucidated.
Methods:   In the current study we measured IR with the euglycemic insulin clamp technique, and assessed cognitive function in 13 elderly diabetic patients (mean age, 69.1 ± 4.4). Several tests to assess cognitive function including Mini-Mental State Examination (MMSE) were performed, and clinical indices were evaluated. IR was evaluated by metabolic clearance rates (MCR).
Results:   The Spearman's rank correlation coefficient between MCR and MMSE scores was 0.587 ( P  = 0.035). When subjects were divided into two groups at the median MCR (5.0 mL/kg/min), the lower MCR (high IR) group ( n  = 5) had significantly lower MMSE scores than the higher group ( n  = 8). The Spearman's rank correlation coefficient was –0.641 ( P  = 0.018) between hs-CRP and MMSE scores. When subjects were divided into two groups at the median of high-sensitivity C-reactive protein (hs-CRP) (594.0 µg/dL), the higher hs-CRP group ( n  = 6) had significantly lower MMSE scores than the lower group ( n  = 7).
Conclusion:   The current study shows that higher IR measured with the euglycemic insulin clamp technique and higher hs-CRP is associated with lower MMSE scores in non-demented diabetic elderly patients.     

Decline in cognitive function and risk of elder self-neglect: finding from the Chicago Health Aging Project

OBJECTIVES: To examine the longitudinal association between decline in cognitive function and risk of elder self‐neglect in a community‐dwelling population. DESIGN: Prospective population‐based study. SETTING: Geographically defined community in Chicago. PARTICIPANTS: Community‐dwelling subjects reported to the social services agency from 1993 to 2005 for self‐neglect who also participated in the Chicago Health Aging Project (CHAP). Of the 5,519 participants in CHAP, 1,017 were reported to social services agency for suspected elder self‐neglect from 1993 to 2005. MEASUREMENTS: Social services agency identified reported elder self‐neglect. The primary predictor was decline in cognitive function assessed using the Mini‐Mental State Examination (MMSE), the Symbol Digit Modalities Test (Executive Function), and immediate and delayed recall of the East Boston Memory Test (Episodic Memory). An index of global cognitive function scores was derived by averaging z‐scores of all tests. Outcome of interest was elder self‐neglect. Logistic and linear regression models were used to assess these longitudinal associations. RESULTS: After adjusting for potential confounding factors, decline in global cognitive function, MMSE score, and episodic memory were not independently associated with greater risk of reported and confirmed elder self‐neglect. Decline in executive function was associated with greater risk of reported and confirmed elder self‐neglect. Decline in global cognitive function was associated with greater risk of greater self‐neglect severity (parameter estimate=0.76, standard error=0.31, P=.01). CONCLUSION: Decline in executive function was associated with risk of reported and confirmed elder self‐neglect. Decline in global cognitive function was associated with risk of greater self‐neglect severity.     

脑白质高信号对帕金森病运动症状和认知损害的影响

目的探讨脑白质高信号(WMH)对帕金森病(PD)运动症状和认知损害的影响。方法回顾性纳入315例PD患者,根据Fazekas量表评分分为轻度WMH组191例,中度WMH组74例,重度WMH组50例。收集脑血管病相关危险因素,Hoehn-Yahr(H-Y)分级、世界运动障碍协会统一帕金森病评定量表第三部分(MDS-UPDRSⅢ)总分及震颤、强直、运动迟缓、步态姿势异常评分评估运动症状,用简易智能状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估认知功能,用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评估情绪,用3T MRI及Fazekas量表评估WMH程度,用Spearman相关和多元线性回归分析。结果 3组年龄、起病年龄、病程、MMSE和MoCA评分比较,有统计学差异(P<0.05,P<0.01)。3组H-Y分级、MDS-UPDRSⅢ总分、震颤、强直、运动迟缓、步态姿势异常、HAMA、HAMD评分及体位性低血压比例比较,无统计学差异(P>0.05)。多元线性回归分析校正年龄、病程、起病年龄、MoCA、同型半胱氨酸、缺血性脑卒中、高血压、吸烟、性别、体质量指数和心脏病等因素后,WMH与MMSE仍显著相关(β=-0.183,95%CI:-0.134^-0.007,P=0.029)。脑室旁WMH(r=-0.246,P=0.000;r=-0.235,P=0.000)和深部WMH(r=-0.192,P=0.001;r=-0.187,P=0.001)与MMSE和MoCA呈显著负相关。WMH与PD运动症状不相关(P>0.05)。结论 WMH对PD认知损害影响明显,临床需警惕PD伴发WMH,脑血管病二级预防可能对PD患者认知减退有潜在预防作用。     

Prevalence and characteristics of older community residents with mild cognitive decline

Background: Cognitive impairment is a major health issue, but epidemiological data on mild cognitive decline have been almost absent in Japan. Methods: Of all residents aged 65 years and over living in Yoita town, Niigata Prefecture, Japan in the year 2000 (n = 1673), 1544 participated in the interview survey held at community halls or at home (92.3% response). They underwent the Mini‐Mental State Examination (MMSE) for assessment of cognitive function and answered questionnaires comprising socio‐demographic, psychological, physical and medical, and social activity items. Higher‐level functional capacities were evaluated with the Tokyo Metropolitan Index of Competence (TMIG‐Index of Competence). According to subject’s age and MMSE score, all subjects were classified into 3 groups: control (MMSE > 1 SD below age‐specific means), mild cognitive decline (MMSE ≥ 21 and ≤ 1 SD below age‐specific means), and severe cognitive decline (MMSE ≤ 20), and compared various characteristics among these groups. Results: Mean MMSE score of the subjects showed a linear decline with advancing age. Among the participants, 232 (15.2%) were classified as mild cognitive decline. Compared with the controls, the subjects with mild cognitive decline reported poorer subjective health, more depressive moods, more history of stroke, more prevalence of basic activity of daily living (BADL) disability, and lower higher‐level functional capacity, even after controlling for possible confounding factors. They also reported a low level of social activities: both participating in group activities and enjoying hobbies were less frequent. Their food intake pattern tended to be monotonous. Conclusions: Older persons with mild cognitive decline comprised a substantial proportion (15.2%) of the community‐dwelling older population. In addition to lower cognitive function, they had lower levels of functional capacity and social activity.     

脑小血管病患者多模态磁共振成像特征及其与认知功能损伤的相关性分析

目的分析脑小血管病(CSVD)患者多模态磁共振成像(MRI)特征及其与认知功能损伤的相关性。方法选取2017—2018年无锡市第五人民医院神经内科收治的CSVD患者184例,根据多模态MRI检查结果分为腔隙性脑梗死(LI)组(n=55)、脑白质高信号(WMH)组(n=48)、脑微出血(CMB)组(n=41)及合并组(n=40);另选取同期体检健康者42例作为对照组。比较五组受试者认知功能指标〔包括简易智能精神状态检查量表(MMSE)评分、蒙特利尔认知评估量表(MoCA)评分、认知障碍发生率、连线测验(TMT)时间、数字符号编码测验(SDMT)评分、数字广度测验(DST)评分、画钟测验(CDT)及词语流畅性测验(VFT)评分〕,有无认知障碍患者LI、CMB发生率及脑白质病变分级;LI、CMB病灶及脑白质病变分级与CSVD患者MoCA评分的相关性分析采用Spearman秩相关分析。结果LI组、WMH组、CMB组及合并组患者MMSE评分、MoCA评分、SDMT评分、DST评分、CDT评分及VFT评分低于对照组,认知障碍发生率高于对照组,TMT时间长于对照组(P<0.05);合并组患者MMSE评分、MoCA评分、SDMT评分、DST评分、CDT评分及VFT评分低于LI组、WMH组、CMB组,认知障碍发生率高于LI组、WMH组、CMB组,TMT时间长于LI组、WMH组、CMB组(P<0.05)。有认知障碍患者LI、CMB发生率高于无认知障碍者,脑白质病变分级劣于无认知障碍者(P<0.05)。Spearman秩相关分析结果显示,LI病灶(rs=-0.340)、CMB病灶(rs=-0.290)及脑白质病变分级(rs=-0.213)与CSVD患者MoCA评分呈负相关(P<0.05)。结论CSVD患者存在认知功能损伤,合并2种及以上MRI异常表现的CSVD患者认知功能损伤更严重,且多模态MRI检查结果LI、CMB病灶及脑白质病变分级与CSVD患者认知功能损伤程度有关。     

Factors related to discrepancy in evaluation on functional capacity between reports by community-dwelling older people with cognitive decline and their family members

Overestimation or underestimation of functional capacity in community-dwelling older people with cognitive impairment was evaluated between the responses of subjects and family members (proxies) by cognitive function level. Out of all the residents aged 65 years and over living in Yoita town, Niigata Prefecture in 2000 (n = 1,673), 1,544 voluntarily participated in the interview survey held at community halls or at home (92.3% response). They underwent the Mini-Mental State Examination (MMSE) for assessment of cognitive function and answered questionnaires comprising socio-demographic, psychological, physical and medical, and social activity items (2000/11). According to the age of the subject and MMSE score, we defined cognitive decline (MMSE scores < 1 SD below age-specific means, n = 371). 158 pairs among 371 subjects with cognitive decline and their proxies participated in a follow-up survey (2001/11). The subjects themselves underwent MMSE again. 136 subject-proxy pairs reported any complaints of memory-related problem and evaluated higher-level functional capacity (TMIG-IC, Tokyo Metropolitan Institute of Gerontology Index of Competence). We established criteria at follow-up survey as follows: control (n = 29), MMSE scores > 1 SD below age-specific means and CDR (Clinical Dementia Rating) = 0: mild cognitive decline (MCD) (n = 54), 21 < or = MMSE scores < 1 SD below age-specific means or CDR = 0.5); and severe cognitive decline (SCD) (n = 53), MMSE scores 20 < or = CDR > 0.5. SCD subjects significantly overestimated total and Instrumental Self-Maintenance scores in TMIG-IC more than control or SCD subjects. Multiple logistic regression analyses indicated that complaints of memory by the proxy, response by spouse, and higher levels of education were extracted as significantly independent variables affecting overestimation for functional capacity. On the other hand, aging affected underestimation.     

Brain lesions, hypertension and cognitive ageing in the 1921 and 1936 Aberdeen birth cohorts

The objectives of this study are to model the relative effects of positive (childhood intelligence) and negative (magnetic resonance imaging (MRI)-derived white matter hyperintensities (WMH)) predictors of late-life intelligence in two well-characterised normal cohorts aged 68 and 78 and to measure the influence of hypertension on WMH and lifelong cognitive change. The Scottish Mental Surveys of 1932 and 1947 tested the intelligence of almost all school children at age 11. One hundred and one participants born in 1921 and 233 participants born in 1936 had brain MRI, with measurement of WMH using Scheltens‘ scale, and tests of late-life fluid intelligence. Structural equation models of the effect of childhood intelligence and brain WMH on the general intelligence factor ‘g’ in late life in the two samples were constructed using AMOS 18. Similar models were constructed to test the effect of hypertension on WMH and lifelong cognitive change. Fluid intelligence scores were lower and WMH scores were higher in the older samples. Hypertensive participants in both samples had more WMH than normotensive participants. The positive influence of childhood intelligence on ‘g’ was greater in the younger sample. The negative effect of WMH on ‘g’ was linear and greater in the older sample due to greater WMH burden. The negative effect of hypertension on lifelong cognitive ageing was all mediated via MRI-derived brain WMH. The positive relationship between childhood and late-life intelligence decreases with age. The negative relationship between WMH and late-life intelligence is linear and increases with age.     

阿尔茨海默病认知功能与磁共振成像测量海马和侧脑室颞角的相关性

目的探讨轻、中度阿尔茨海默病(AD)认知功能和MRI测量海马和侧脑室颞角的相关性。方法对31例AD患者(AD组)及30例健康体检者(对照组)进行认知功能量表的检测,包括简易智能状态检查表(MMSE)、日常生活能力量表(ADL)、Pfeffer功能活动调查表(POD)、Fuld物体记忆测验(FOM)、快速词汇测验(RVR)、数字广度测验(DS)、积木测验(BD)等,同时应用MRI测量颅腔的海马体积和侧脑室颞角宽度。结果海马体积、侧脑室颞角宽度AD组与对照组比较差异显著(P<0.01)。海马体积、侧脑室颞角宽度与MMSE、ADL、POD、FOM有相关性,其与DS、BD无相关性,其中海马体积与MMSE、FOM密切相关。结论AD患者的认知功能评定与MRI脑结构测量有一定的相关性,认知功能和MRI脑结构测量可为临床诊断和治疗提供可靠依据。     

Sex hormones and cognitive function in older men

OBJECTIVES: Recent studies have suggested that estrogen may improve cognitive function or prevent cognitive decline in older women. Little research has been conducted on exogenous or endogenous sex hormones and cognition in older men, yet it has been hypothesized that testosterone, either directly or by conversion to estrogens, may improve cognitive function. We investigated whether serum level of testosterone and estradiol is associated with cognition in older community-dwelling men. DESIGN: A cross-sectional study. SETTING: Population-based listings in the Monongahela Valley near Pittsburgh, Pennsylvania. PARTICIPANTS: Three hundred ten men (mean age +/- standard deviation = 73.0 +/- 7.1) who were part of a cohort study. MEASUREMENTS: We measured cognitive function using the Mini-Mental State Examination (MMSE), Trails B, and Digit Symbol. Sex hormone levels were determined by radioimmunoassay from serum obtained at the time of cognitive testing and analyzed by tertile. RESULTS: No consistent association between total testosterone level and cognitive test scores was observed. However, men with high bioavailable (loosely protein-bound) testosterone had better cognitive test scores on all three tests (P < or =.001). Total estradiol levels were associated with worse cognitive scores on Digit Symbol (P <.001) and Trails B (P =.002), but bioavailable estradiol levels were not associated with cognitive function. Level of sex hormone binding globulin (SHBG) was negatively associated with cognitive scores on all three tests (P < or =.001). After adjusting for age and education, the statistical significance lessened for bioavailable testosterone (MMSE, P =.086; Digit Symbol, P =.047; Trails B, P =.076) and became nonsignificant for SHBG (all cognitive tests P>.10). CONCLUSIONS: Our findings support the hypothesis that higher levels of bioavailable testosterone, but not of bioavailable estradiol, are associated with better cognitive function in older men. In addition, bioavailable measures of testosterone may better reflect hormone levels available to the brain and thus be more closely associated with central nervous system outcomes such as cognition. Future studies, especially randomized trials, should be undertaken to determine whether testosterone may protect against cognitive decline in older men.