Improvement of Screening Accuracy of Mini-Mental State Examination for Mild Cognitive Impairment and Non-Alzheimer's Disease Dementia by Supplementation of Verbal Fluency Performance

Objective

This study aimed to investigate whether the supplementation of Verbal Fluency: Animal category test (VF) performance can improve the screening ability of Mini-Mental State Examination (MMSE) for mild cognitive impairment (MCI), dementia and their major subtypes.

Methods

Six hundred fifty-five cognitively normal (CN), 366 MCI [282 amnestic MCI (aMCI); 84 non-amnestic MCI (naMCI)] and 494 dementia [346 Alzheimer''s disease (AD); and 148 non-Alzheimer''s disease dementia (NAD)] individuals living in the community were included (all aged 50 years and older) in the study.

Results

The VF-supplemented MMSE (MMSE+VF) score had a significantly better screening ability for MCI, dementia and overall cognitive impairment (MCI plus dementia) than the MMSE raw score alone. MMSE+VF showed a significantly better ability than MMSE for both MCI subtypes, i.e., aMCI and naMCI. In the case of dementia subtypes, MMSE+VF was better than the MMSE alone for NAD screening, but not for AD screening.

Conclusion

The results support the usefulness of VF-supplementation to improve the screening performance of MMSE for MCI and NAD.     

Prevalence of Alzheimer's Dementia and Its Risk Factors in Community-Dwelling Elderly Koreans

Objective

We estimated the prevalence of Alzheimer''s dementia (AD) and mild cognitive impairment (MCI) and their risk factors in an urban community setting, focusing especially on metabolic syndrome.

Methods

A two-phase investigation based on a door-to-door survey was performed. In Phase I, we administered the Korean version of the Mini-Mental State Examination (MMSE-KC) of the Consortium to Establish a Registry for Alzheimer''s disease (CERAD-K). Assessment Packet and the Korean version of the Geriatric Depression Scales (GDS-K) to all 706 participants aged 65 years or older. In Phase II of the study, 175 persons underwent physical and neurological examinations according to the protocol of the CERAD-K clinical assessment battery [CERAD-K (C)] and the neuropsychological assessment battery [CERAD-K (N)]. We also examined the association between cognitive decline and metabolic syndrome. AD and MCI were defined using the DSM-IV-TR criteria and the Clinical Dementia Rating (CDR) scales.

Results

The mean age (±SD) of the subjects was 74.3±16.7 years and the ratio of males to females was 53.2 to 46.8. The prevalence of Alzheimer''s dementia was 9.0%, while that of MCI was 32.9%. Old age and lower educational level had significant associations with cognitive decline in the elderly, but gender, years of alcohol intake or smoking, and metabolic syndrome were not associated with AD or MCI.

Conclusion

In this study, metabolic syndrome was not associated with Alzheimer''s AD or MCI. Information regarding an association between Alzheimer''s dementia and metabolic syndrome in this study will be helpful in formulating future public health policy and prevention strategies in Korea.     

Frontal Dysfunction Underlies Depression in Mild Cognitive Impairment: A FDG-PET Study

Objective

Depression is a very common symptom in people with mild cognitive impairment (MCI), a preclinical stage of Alzheimer''s disease (AD), and in those with clinically evident AD. Moreover, MCI individuals with depression show a higher conversion rate to clinical AD than those without depression. This study aimed to elucidate the functional neuroanatomical substrate of depression in MCI.

Methods

Thirty-six patients were recruited from a University Hospital-based cohort; 18 of these subjects had MCI with depression (MCI_D); the remaining 18 subjects were age- and gender-matched, and had MCI with no depression (MCI_ND). For comparison, 16 cognitively normal (CN) elderly individuals were also included. All subjects underwent Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scanning and regional cerebral glucose metabolism was compared among the three groups by a voxel-based method. The relationship between severity of depression, as measured by Hamilton Rating Scale for Depression (HRSD) scores, and glucose metabolism was also investigated.

Results

MCI_D showed lower glucose metabolism in the right superior frontal gyrus than MCI_ND. There was a significant negative correlation between HRSD score and glucose metabolism at the same frontal region for overall MCI subjects. When compared with CN, both MCI_D and MCI_ND showed decreased glucose metabolism in the precuneus, while MCI_D had, in addition, reduced metabolism in other diffuse brain regions.

Conclusion

Given previous observations on depression in AD, our results suggest that functional disruption of the frontal region, known to be associated with primary or other secondary depression, underlies depression in preclinical AD as well as clinically evident AD.     

A Normative Study of the Disability Assessment for Dementia in Community-Dwelling Elderly Koreans

Objective

We investigated demographic influences on Korean version of Disability Assessment for Dementia (DAD-K) performance and developed normative data for DAD-K.

Methods

The DAD-K was administered to 2362 normal controls (NCs), 296 patients with mild cognitive impairment (MCI) and 293 patients with Alzheimer''s disease (AD). MANOVA and ROC curve analysis were used to compare DAD-K performance and the diagnostic accuracy of DAD-K, respectively. The demographic influence on DAD-K scores was analyzed by multiple linear regression and ANOVA. Normative DAD-K data were calculated using natural logarithmic transformation.

Results

All DAD-K scores were significantly different among groups (p<0.001). Post hoc analysis showed that instrumental activities of daily living (IADL), executive function and DAD-K total scores began to decline significantly in the very mild stage of AD, whereas the basic activities of daily living (BADL) scores began to decline in the mild stage of AD. The area under the ROC curve differentiating MCI or AD from NC was 0.737 and that differentiating AD from MCI or NC was 0.911. IADL and planning and organization scores were influenced by age and education and performance and DAD-K total scores were influenced by education.

Conclusion

The demographic influences on DAD-K scores are not conspicuous and are mainly limited to the IADL and planning and organization scores. Unitary or minimally stratified norms for a specific population were developed for DAD-K application. Our results suggest that the DAD-K is useful for differentiating NC or MCI from AD but not as powerful for differentiating NC from MCI.     

Hormones and dementia – a comparative study of hormonal impairment in post-menopausal women, with and without dementia

Context

Women seem to be more vulnerable to dementia, particularly Alzheimer’s disease (AD), than men. There is controversy among studies correlating estrogen deficit to cognitive impairment. Because of the sudden drop of estrogens in menopause, this hormonal deficit could represent one of the risk factors for the larger incidence and prevalence of AD in post-menopausal women.

Rationale

We therefore wanted to find out if post-menopausal women with dementia, or even in a prior stage, mild cognitive impairment (MCI), would have a more significant deficit of estrogens than post-menopausal women without dementia, or any other type of cognitive problem.

Objectives

The aim of this study was to detect possible differences of the sex hormone levels among post-menopausal women, simultaneously affected by MCI or dementia, in comparison with a control group without cognitive impairment.

Design, setting, and participants

A small, multicenter, prospective study was performed on 82 post-menopausal women (41 cases, 41 controls), aged 45–81 years, to investigate their sex hormone balance. The diagnosis of dementia was made according to ICD 9 or 10 and DSM III-R or IV appropriate to the time interval. The diagnosis of probable AD followed the NINCDS-ADRDA criteria. MCI met the Paquid-study criteria. Blood was analyzed in qualified centers for LH, FSH, and 17-β-estradiol. All women went through a thorough psychiatric examination and those with a suspected hormonal impairment were examined by a gynecologist.

Results

15 cases (36.6%) had impaired hormonal function, compared with 8 controls (19.5%). Of the 15 cases with hormonal impairment, 9 had MCI.

Conclusions

These preliminary data stress a considerable difference between the sex hormone status of these two populations, showing a tendency towards a more accentuated estrogen deficit linked to cognitive deficit. Enlarging the sample and following the evolution could bring more interesting data.     

Automated Classification to Predict the Progression of Alzheimer's Disease Using Whole-Brain Volumetry and DTI

Objective

This study proposes an automated diagnostic method to classify patients with Alzheimer''s disease (AD) of degenerative etiology using magnetic resonance imaging (MRI) markers.

Methods

Twenty-seven patients with subjective memory impairment (SMI), 18 patients with mild cognitive impairment (MCI), and 27 patients with AD participated. MRI protocols included three dimensional brain structural imaging and diffusion tensor imaging to assess the cortical thickness, subcortical volume and white matter integrity. Recursive feature elimination based on support vector machine (SVM) was conducted to determine the most relevant features for classifying abnormal regions and imaging parameters, and then a factor analysis for the top-ranked factors was performed. Subjects were classified using nonlinear SVM.

Results

Medial temporal regions in AD patients were dominantly detected with cortical thinning and volume atrophy compared with SMI and MCI patients. Damage to white matter integrity was also accredited with decreased fractional anisotropy and increased mean diffusivity (MD) across the three groups. The microscopic damage in the subcortical gray matter was reflected in increased MD. Classification accuracy between pairs of groups (SMI vs. MCI, MCI vs. AD, SMI vs. AD) and among all three groups were 84.4% (±13.8), 86.9% (±10.5), 96.3% (±4.6), and 70.5% (±11.5), respectively.

Conclusion

This proposed method may be a potential tool to diagnose AD pathology with the current clinical criteria.     

Plasma Total Homocysteine Levels are not Associated with Medial Temporal Lobe Atrophy, but with White Matter Changes in Alzheimer's Disease

Background and purpose

Elevated plasma total homocysteine (tHcy) levels are reported to be associated with an increased risk of Alzheimer''s disease (AD). However, the mechanism by which homocysteine contributes to the pathogenesis of AD is as yet unknown. The aim of this study was to elucidate the relationship between white matter changes (WMC) and medial temporal lobe atrophy (MTA) on brain magnetic resonance imaging (MRI), and plasma levels of tHcy in AD patients.

Methods

Seventy-two patients with a clinical diagnosis of probable AD were recruited to the study. Plasma tHcy levels, vascular risk factors, and WMC and MTA on brain MRI were evaluated in all patients. The AD patients were classified into two groups: those with no or minimal WMC (69.2±8.8 years, mean±SD, n=36) and those with moderate-to-severe WMC (74.6±4.6 years, n=36) on brain MRI.

Results

In a univariate logistic regression analysis, the risk of moderate-to-severe WMC in AD was significantly associated with increasing age, female gender, lower education level, hypertension, high plasma tHcy levels, and lower Mini-Mental State Examination (MMSE) score. Multivariate logistic regression analysis revealed only high plasma tHcy as the independent and significant risk factor for moderate-to-severe WMC [odds ratio (OR; adjusted for age, gender, education level, MMSE score, and hypertension comparing the top tertile - tHcy levels ≥12.9 µmol/L - with the bottom tertile - tHcy levels ≤9.4 µmol/L)=7.35; 95% confidence interval, confidence interval=1.36-39.84; p=0.02], and age as a borderline significant risk factor (OR=1.08, 95% CI=0.99-1.19, p=0.09) in AD patients. Plasma tHcy levels were not correlated significantly with either right or left MTA.

Conclusions

Our results suggest that the vascular pathway mediates the association between elevated plasma tHcy levels and AD.     

Decreased Serum Brain-Derived Neurotrophic Factor Levels in Elderly Korean with Dementia

Objective

The primary purpose of this study was to investigate the differences in the serum brain-derived neurotrophic factor (BDNF) level between elderly Korean people over 65 years with and without dementia.

Methods

171 individuals over 65 years were enrolled in this study. Screening for cognitive impairments was carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). One hundred thirty-two subjects scored below 1.5 standard deviations (SD) of the mean MMSE-KC score, and these were evaluated using the Consortium to Establish a Registry for Alzheimer''s Disease, Korean version (CERAD-K) and the Geriatric Depression Scale (GDS). The Clinical Dementia Rating Scale (CDRS) and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria were used for further evaluation. Subjects with a CDRS score of 1 or higher were classified as having Alzheimer''s disease (AD), and subjects with a CDRS score of 0.5 were classified as having a mild cognitive impairment (MCI). Subjects with a CDRS score of 0 were classified as having aging-associated cognitive decline (AACD). Serum BDNF levels were analyzed using the enzyme-linked immunosorbent assay (ELISA) method.

Results

The serum BDNF levels were significantly lower in the subjects with MCI and AD compared with the healthy controls (p<0.01). A significant correlation was found between the total MMSE-KC score and serum BDNF level (r=0.295; p<0.01). However, no significant correlation was observed between the severity of MMSE-KC and the total GDS score. A significant difference was found in the total score of GDS between the AACD group and subjects with AD (p<0.05).

Conclusion

This study suggested that BDNF might be involved in the pathophysiology of cognitive decline in elderly people.     

The Effect of Cognitive Training in Patients with Mild Cognitive Impairment and Early Alzheimer's Disease: A Preliminary Study

Background and Purpose

The objective of this study was to determine the benefits of cognitive training in patients with amnestic mild cognitive impairment (aMCI) and those with early Alzheimer''s disease (AD).

Methods

Eleven patients with aMCI and nine with early AD (stage 4 on the Global Deterioration Scale) participated in this study. Six participants with aMCI and six with AD were allocated to the cognitive training group, while five participants with aMCI and three with AD were allocated to a wait-list control group. Multicomponent cognitive training was administered in 18 weekly, individual sessions. Outcome measures were undertaken at baseline, and at 2 weeks and 3 months of follow-up.

Results

In the trained MCI group, there were significant improvements in the delayed-recall scores on the Seoul Verbal Learning Test at both the 2-week and 3-month follow-ups compared with baseline (baseline, 1.6±1.5; 2 weeks, 4.4±1.5, p=0.04; 3 months, 4.6±2.3, p=0.04). The phonemic fluency scores (1.0±0.8 vs. 5.0±1.8, p=0.07) and Korean Mini-Mental State Examination scores (18.8±0.5 vs. 23.8±2.2, p=0.07) also showed a tendency toward improvement at the 2-week follow-up compared to baseline in the trained AD group.

Conclusions

This study provides evidence of the effectiveness of cognitive training in aMCI and early AD. The efficacy of cognitive training programs remains to be verified in studies with larger samples and a randomized design.     

Cerebrospinal fluid beta-amyloid 1-42 concentration may predict cognitive decline in older women

Background

Low levels of cerebrospinal fluid (CSF) β‐amyloid 1–42 (Aβ42) and high total tau (T‐tau) are diagnostic for manifest Alzheimer''s disease. It is not known, however, whether these biomarkers may be risk indicators for cognitive decline in otherwise healthy older people.

Methods

The longitudinal relationship between CSF markers, Aβ42 and T‐tau, measured in 1992, and change in Mini‐Mental State Examination (ΔMMSE) score between 1992 and 2002 were investigated in 55 women (aged 70–84 years, mean (SD) MMSE score = 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992–3.

Results

Over the 8‐year follow‐up period, ΔMMSE (range =  +3 to −21 points) was correlated with Aβ42 (Spearman''s r = 0.40, p = 0.002), such that lower levels of Aβ42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman''s r = 0.34, p = 0.019). A multivariate logistic regression model predicting a decline of ⩾5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8‐year follow‐up period (observed in four women), including age, education, Aβ42 and T‐tau as covariates, showed that Aβ42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml Aβ42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013).

Conclusions

Low levels of CSF Aβ42 may predict cognitive decline among older women without dementia.Alzheimer''s disease (AD) is rapidly increasing with advancing age, with reported prevalence estimates of 30% at age 85 years, and as high as 50% at age 95 years.¹ AD is expected to reach epidemic proportions between 2010 and 2050, when the number of people with the disease is projected to be more than double. Juxtaposed against this harrowing background is the fact that risk indicators for AD in healthy older people are lacking.β‐amyloid 1–42 (Aβ42) and total tau (T‐tau) are two known biomarkers of manifest AD that are detectable in cerebrospinal fluid (CSF). Low levels of CSF Aβ42 and high levels of CSF T‐tau in cases of AD have been described in both clinical and population‐based samples.^2,3,4,5,6 Aβ42 is the 42‐amino acid fragment of amyloid precursor protein. It accumulates in the brain and is the principal component of senile plaques. Aβ42 in CSF has been suggested to reflect the deposition of β‐amyloid in senile plaques, with lower levels excreted to the CSF. T‐tau is a microtubule‐associated protein that, on hyperphosphorylation, is the primary component of neurofibrillary tangles in AD.⁷ T‐tau in CSF has been suggested to reflect neuronal and axonal degeneration in AD and/or the formation of neurofibrillary tangles.⁷ Thus, both these markers potentially reflect central pathogenic processes in a brain with AD. In addition, clinical evidence is accumulating that low levels of CSF Aβ42 and high levels of T‐tau may also be useful for predicting progression of mild cognitive impairment (MCI) to AD.⁸Despite known associations between CSF Aβ42 and T‐tau, and manifest AD, little is known about the utility of these biomarkers as risk indicators of cognitive decline in healthy older people who are representative of the population. Thus, we investigated whether lower CSF Aβ42 and higher CSF T‐tau predict cognitive decline, as measured using change in Mini‐Mental State Examination (ΔMMSE) score over 8 years, in a population‐based sample of older women aged 70–84 years.     

Impairment of Instrumental Activities of Daily Living in Patients with Mild Cognitive Impairment

Objective

This study was conducted to examine the following: whether patients with mild cognitive impairment (MCI) show impairments in instrumental activities of daily living (IADL) as compared to controls; to identify the functional sub-domains of instrumental activities of daily living (IADL) that are affected in MCI and, finally, to identify the Seoul-Instrumental Activities of Daily Living (S-IADL) scale cut-off score that best differentiated between MCI and controls.

Methods

This study was carried out at the geropsychiatry clinic, university hospital. The study participants included 66 patients with MCI and 61 normal elderly. The S-IADL and Seoul-Activities of Daily Living (S-ADL) scales were administered to the main caregivers of all participants in order to assess everyday functioning.

Results

The total S-IADL score was significantly higher in the patients with MCI [mean (SD) score=4.47 (2.06)] than in the controls [mean (SD) score=1.44 (1.65)] (p<0.001). The patients with MCI performed significantly worse on IADLs, such as the ability to use the telephone, prepare meals, take medication, manage belongings, keep appointments, talk about recent events, and perform leisure activities/hobbies (p<0.05). The S-IADL scale discriminated well between patients with MCI and controls (Area Under Curve=87%).

Conclusion

The patients with MCI showed impairments in the ability to perform complex ADL in comparison to healthy controls. IADLs related to memory and frontal/executive functioning were particularly affected in MCI.     

Combining olfaction and cognition measures to screen for mild cognitive impairment

Purpose:

This exploratory study examined the relationship between performance on the University of Pennsylvania Smell Identification Test (UPSIT) and the Addenbrooke’s Cognitive Examination (ACE) to identify a possible association between olfaction and mild cognitive impairment(MCI).

Design and Methods:

54 community-dwelling older (ages 49–91) volunteers were given the UPSIT and ACE.

Results:

The ACE identified 7 subjects (13%) who had probable MCI. UPSIT total scores were significantly related to ACE total scores (r = 0.37, p = 0.005). Four specific odorants (mint, lime, chocolate, and cheddar cheese) from the UPSIT identified 4 of the 7 (57.1%) probable MCI subjects. The prevalence rate of MCI in subjects over 65 was 19.4%.

Implications:

Selective odorants in UPSIT used with ACE show promise as a non-invasive method of detecting MCI in community dwelling elders. Detection of MCI could facilitate earlier interventions and treatment of dementia.     

Medial Temporal Atrophy and Memory Dysfunction in Poststroke Cognitive Impairment-No Dementia

Background and Purpose

It was recently reported that the prevalence of poststroke memory dysfunction might be higher than previously thought. Stroke may exist concomitantly with underlying Alzheimer''s disease (AD), and so we determined whether post-stroke memory dysfunction indicates manifestation of underlying subclinical AD.

Methods

Of 1201 patients in a prospective cognitive assessment database, we enrolled subjects with poststroke amnestic vascular cognitive impairment-no dementia (aVCIND; n=48), poststroke nonamnestic vascular cognitive impairment-no dementia (naVCIND; n=50), and nonstroke amnestic mild cognitive impairment (aMCI; n=65). All subjects had cognitive deficits, but did not meet the criteria for dementia. A standardized neuropsychological test battery and magnetic resonance imaging were performed at least 90 days after the index stroke (mean, 473 days). Visual assessment of medial temporal atrophy (MTA) was used as a measure of underlying AD pathology.

Results

The MTA score was significantly lower in the naVCIND group (0.64±0.85, mean±SD) than in the aVCIND (1.10±1.08) and aMCI (1.45±1.13; p<0.01) groups. Multivariable ordinal logistic regression analysis revealed that compared with naVCIND, aVCIND [odds ratio (OR)=2.69; 95% confidence interval (CI)=1.21-5.99] and aMCI (OR=5.20; 95% CI=2.41-11.23) were significantly associated with increasing severity of MTA.

Conclusions

Our findings show that compared with poststroke naVCIND, the odds of having more-severe MTA were increased for poststroke aVCIND and nonstroke aMCI.     

Topographical Disorientation in Mild Cognitive Impairment: A Voxel-Based Morphometry Study

Background and Purpose

To assess the neural substrates underlying topographical disorientation (TD) in patients affected by mild cognitive impairment (MCI), forty-one patients diagnosed with MCI and 24 healthy control individuals were recruited.

Methods

TD was assessed clinically in all participants. Neurological and neuropsychological evaluations and a volumetric-head magnetic resonance imaging scan were performed in each participant. Voxel-based morphometry was used to compare patterns of gray-matter atrophy between patients with and without TD, and a group of normal controls.

Results

We found TD in 17 out of the 41 MCI patients (41.4%). The functional abilities were significantly impaired in MCI patients with TD compared to in MCI patients without TD. Voxel-based morphometry analyses showed that the presence of TD in MCI patients is associated with loss of gray matter in the medial temporal regions, including the hippocampus and parahippocampal cortex, the fusiform gyrus, the inferior occipital gyrus, the amygdala, and the cerebellum.

Conclusions

The findings found in this study represent the first evidence that the presence of TD in patients with MCI is associated with loss of gray matter in those brain regions that have been documented to be responsible for orientation in both neuropsychological and neuroimaging studies.     

老年抑郁症患者抗抑郁药治疗期间认知与抑郁症状的变化及其与ApoEε4等位基因的关系

Background

Co-occurring cognitive impairment in geriatric depression may not improve with antidepressant treatment and it may progress to dementia.

Aim

Assess the relationship between changes in cognitive and depressive symptoms among patients with geriatric depression and their association with the APOE epsilon 4 allele before and after antidepressant treatment.

Methods

The presence of the APOE epsilon 4 allele was assessed in 64 incident cases of geriatric depression and 31 elderly individuals without depression and the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), digit span test, and Trail Making Tests A and B (TMT-A, TMT-B) were administered to these subjects at baseline and 12 months after baseline, during which time the depressed group received standardized treatment with selective serotonin reuptake inhibitors (SSRIs).

Results

Prior to treatment patients with geriatric depression had significantly worse cognitive functioning than control subjects and 31 (48%) met criteria for mild cognitive impairment (MCI). After treatment depressed patients with and without comorbid MCI both had significant improvements in their depressive and cognitive symptoms, but those with MCI had more residual symptoms. The severity of cognitive symptoms was not associated with the severity of depressive symptoms at baseline, but they were positively correlated at the 12-month follow-up. The APOE epsilon 4 allele was identified in 14% (9/64) of the patients and in 3% (1/31) of the controls (Fisher''s Exact Test, p=0.158). Compared to depressed patients without the allele, depressed patients with the allele had more severe cognitive deficits both before and after treatment, though only some of these differences were statistically significant.

Conclusions

There is substantial cognitive impairment in elderly individuals with geriatric depression. Both the depressive and cognitive symptoms improve with standard SSRI treatment, but individuals with comorbid MCI have more residual depressive and cognitive symptoms after treatment. The APOE epsilon 4 allele is associated with greater cognitive impairment in geriatric depressed patients and may be associated with less responsiveness of cognitive symptoms to antidepressant treatment.     

Construct validity and reliability of the Test Your Memory Chinese version in older neurology outpatient attendees

Background

Early distinguishing the cognitive impairment from healthy population is crucial to delay the progression of mild cognitive impairment (MCI) and Alzheimer disease (AD). Test Your Memory (TYM) has been proved to be a valid and reliable screening instrument for AD and MCI. This study aimed to develop a culturally appropriate and functional Standard Mandarin Chinese translation of the TYM, and to evaluate its reliability and validity in detecting AD and MCI in Chinese.

Methods

182 subjects with AD/MCI and 55 healthy controls were recruited to participate in this study, and everyone undergo the test of Standard Mandarin Chinese version of the TYM (TYM-CN), Mini-mental State Examination (MMSE), Montreal cognitive assessment (MoCA-BJ), and Clinical Dementia Rating (CDR) Scale. Concurrently, all the subjects with AD/MCI received the general physical and neurologic examinations, extensive laboratory tests, and brain computed tomography/magnetic resonance imaging (MRI). Of which, 90 subjects were asked to complete the re-test of TYM-CN at 3 weeks after the initial visit. Intra-class correlation coefficient (ICC) and Cronbach’s alpha was used to assess the test–retest reliability and the internal consistency. The validity, sensitivity and specificity were also analyzed. One-way analysis of variance, χ² test, correlation analysis, and receiver operating characteristic curve (ROC) analysis were employed, as needed.

Results

The total scores of TYM-CN was 43.89?±?3.44, 40.88?±?4.38, and 29.12?±?7.44 (p?<?0.01) for healthy controls group, MCI group, and AD group, respectively. The ICC for 11 items of TYM-CN ranged from 0.863 (copying) to 0.994 (anterograde), and that of the total scale was 0.993, suggesting an excellent reliability. Furthermore, the significant correlation was also found between TYM-CN and MMSE (r?=?0.76), MoCA-BJ (r?=?0.74), and CDR scores (r?=?0.76), indicating a good validity. A TYM-CN scores?≤?39.5 had 95% sensitivity and 95% specificity in differentiating AD from healthy controls, and that?≤?43.5 had 75% sensitivity and 91% specificity in distinguishing MCI from healthy controls, respectively.

Conclusion

The reliability and validity of the TYM-CN are statistically acceptable for the evaluation of cognitive impairment, which may contribute to neuropsychological tests for the diagnosis of AD and MCI from healthy controls in China.

     

G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease

Objective

We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer''s disease (AD) and normal controls to assess the early phase control defect in cell cycle.

Methods

Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin.

Results

The patients with AD were older than the normal controls (AD 74.03±7.90 yr vs. control 68.28±6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29±6.32% vs. 76.03±9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45±6.09% vs. 6.03±5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects.

Conclusion

The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.     

Circulating plasmalogen levels and Alzheimer Disease Assessment Scale–Cognitive scores in Alzheimer patients

Background

Plasmalogens, which are key structural phospholipids in brain membranes, are decreased in the brain and serum of patients with Alzheimer disease (AD). We performed this pilot study to evaluate the relation between the levels of circulating plasmalogens and Alzheimer Disease Assessment Scale–Cognitive (ADAS-Cog) scores in patients with AD.

Methods

We evaluated participants’ ADAS-Cog scores and serum plasmalogen levels. For the 40 included AD patients with an ADAS-Cog score between 20 and 46, we retested their ADAS-Cog score 1 year later. The levels of docosahexaenoic acid plasmalogen were measured by use of liquid chromatography–tandem mass spectrometry.

Results

We found that the ADAS-Cog score increased significantly in AD patients with circulating plasmalogen levels that were ≤ 75% of that of age-matched controls at entry into the study. There was no change in score among participants with normal serum plasmalogen levels at baseline (> 75%).

Limitations

This was a pilot study with 40 patients, and the results require validation in a larger population.

Conclusion

Our study demonstrates that decreased levels of plasmalogen precursors in the central nervous system correlate with functional decline (as measured by ADAS-Cog scores) in AD patients. The use of both ADAS-Cog and serum plasmalogen data may be a more accurate way of predicting cognitive decline in AD patients, and may be used to decrease the risk of including patients with no cognitive decline in the placebo arm of a drug trial.     

Decreased Vasomotor Reactivity in Alzheimer's Disease

Background

Reduced cerebral blood flow and microvascular abnormalities have been suggested as the vascular pathogenesis of Alzheimer''s disease (AD). Transcranial Doppler sonography (TCD) can be used as a noninvasive method for measuring cerebral vasomotor reactivity (VMR) which represent the capability of arterioles to dilate and constrict in order to maintain cerebral blood flow.

Objective

The objective of this study was to determine whether VMR is decreased in AD patients. Methods: Seventeen consecutive patients who met NINDS-ADRDA criteria for AD, and 17 age- and sex-matched controls were included in this study. MRI and MRA were performed for the grading of white-matter lesions. Patients with cerebral infarct or stenosis of the middle cerebral artery (MCA) were excluded. The fixed TCD probe was used to monitor the mean flow velocity (MFV) in the MCA. A 6-L rebreathing bag was applied to patients for at least 5 minutes to elevate the CO₂ concentration, which was continuously monitored with a capnometer. VMR was calculated as the percentage change in the MFV.

Results

Baseline characteristics - including cerebrovascular risk factors, grades of white-matter lesions, baseline MFV, and pulsatility index - did not differ between the two groups. Mini-Mental State Examination score was significantly low in AD group (20.5 vs. 27.5, p<0.05). VMR was significantly reduced in AD group both in the right-side (24.5% vs. 36.6%, p<0.05) and left-side (20.7% vs. 34.1%, p<0.05) MCAs.

Conclusions

Our finding that VMR is reduced in AD may be suggestive of underlying microangiopathic mechanism in AD patients. Future studies should check the validity of these experimental and hypothesis-generating pilot results.     

Medial temporal atrophy but not memory deficit predicts progression to dementia in patients with mild cognitive impairment

Background

The diagnosis of mild cognitive impairment (MCI) is clinically unhelpful, as many patients with MCI develop dementia but many do not.

Objective

To identify clinical instruments easily applicable in the clinical routine that might be useful to predict progression to dementia in patients with MCI assessed in the outpatient facility of a memory clinic.

Participants and methods

52 dementia‐free patients (mean (standard deviation) age 70 (6) years; 56% women) with MCI, and 65 healthy controls (age 69 (6) years; 54% women) underwent brain magnetic resonance scan with standardised visual assessment of medial temporal atrophy (MTA) and subcortical cerebrovascular lesions (SVLs). Follow‐up assessment occurred 15.4 (SD 3.4) months after baseline to detect incident dementia and improvement, defined as normal neuropsychological performance on follow‐up.

Results

Patients were classified into three groups according to the presence of memory disturbance only (MCI Mem), other neuropsychological deficits (MCI Oth) or both (MCI Mem+). MCI Mem and Mem+ showed MTA more frequently (31% and 47% v 5% and 14% of controls and MCI Oth, p<0.001). 11 patients developed dementia (annual rate 16.5%) and 7 improved on follow‐up. The only independent predictor of progression was MTA (odds ratio (OR) 7.1, 95% confidence interval (CI) 1.4 to 35.0), whereas predictors of improvement were the absence of memory impairment (OR 18.5, 95% CI 2.0 to 171.3) and normal MRI scan (OR 10.0, 95% CI 1.7 to 60.2).

Conclusion

Neuropsychological patterns identify groups of patients with MCI showing specific clinical features and risk of progression to dementia. MTA clinically rated with a visual scale is the most relevant predictor of progression and improvement.The concept of mild cognitive impairment (MCI) was originally coined by Petersen et al¹ to capture the preclinical stages of Alzheimer''s dementia. It is known that the formation of the neuropathological lesions of Alzheimer''s disease occurs decades before the first clinical symptoms.² Memory impairment is typically the initial presentation of Alzheimer''s disease, suggesting that memory disturbance in elderly people may be a sign of the transition phase between normal ageing and Alzheimer''s disease.¹ However, not all patients with MCI deteriorate.³ Available data suggest that the likelihood of a patient with MCI developing Alzheimer''s disease in the long term is around 50%, thus making the diagnosis of MCI in itself clinically unhelpful.⁴Pathological and clinical data indicate that some indicators of Alzheimer''s disease might be used to distinguish those patients with MCI who will progress from those who will not. Some of these indicators, such as hippocampal volumetry,⁵ τ and aβ proteins in the cerebrospinal fluid,⁶ and functional defects in the temporoparietal and posterior cingulate cortex,⁷ require technologically advanced tools and specific competences and are applicable only in specialised centres. Other markers of progression have been proposed, such as the involvement of multiple cognitive domains besides memory,⁸ or medial temporal lobe atrophy (MTA) on magnetic resonance imaging (MRI).⁹ These are more easily assessed in a non‐specialised clinical setting and could be implemented in second level centres.Our study aimed to identify clinical instruments, easily applicable in the clinical routine, that might be useful to predict progression to dementia in patients with MCI.