Development of the Telephone Interview for Cognitive Status (TICS) in Japanese]

In recent years, population of elder people has increased in Japan, following augmentation of the number of people with dementia in Japan. Then it is important to detect cognitive impairment in early stage for adequate treatment, care and prevention. We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls using Telephone Interview for Cognitive Status (TICS), and developing Japanese version of the TICS (TICS-J). The sensitivity and the specificity of the TICS-J to differentiate AD patients from healthy controls was 98.0% and 90.7%, respectively. Pearson's correlation coefficiency between the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the receiver operating curves, the area under the curve for the TICS-J was 98.7% (95% CI: 97.5%-100%). These results indicate that TICS-J is sensitive and specific instrument for differentiating AD patients from healthy controls.     

Validation of the Telephone Interview for Cognitive Status (TICS) in Japanese

BACKGROUND: In recent years, the population of elderly people in Japan with dementia has increased. Detection of cognitive impairment in the early stages is important for adequate treatment, care, and prevention. AIM: To investigate whether the reliability and validity of the instrument would carry over to a different population and language before using it for population-based epidemiological studies. METHODS: We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls (CTL) using the Telephone Interview for Cognitive Status (TICS) and developed the Japanese version of the TICS (TICS-J). We also evaluated combination of another telephone battery, the Category Fluency Test (CF). RESULTS: The sensitivity and specificity of the TICS-J to differentiate AD patients from CTL was 98.0% and 90.7%, respectively. Pearson's correlation coefficient for the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the Receiver Operating Characteristic (ROC), the area under the curve for the TICS-J was 98.7%. The combination of the TICS-J with the CF did not change the validity of the discrimination. CONCLUSION: These results indicated that TICS-J was a sensitive and specific instrument for differentiating AD patients from healthy controls.     

Comparing measures of decline to dementia in amnestic MCI subjects in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set

ABSTRACT Background: Many studies have investigated factors associated with the rate of decline and evolution from mild cognitive impairment (MCI) to Alzheimer's disease (AD) dementia in elderly patients. In this analysis, we compared the rates of decline to dementia estimated from three common global measures of cognition: Mini-Mental State Examination (MMSE) score, Clinical Dementia Rating sum of boxes (CDR-SB) score, and a neuropsychological tests composite score (CS). Methods: A total of 2,899 subjects in the National Alzheimer's Coordinating Center Uniform Data Set aged 65+ years diagnosed with amnestic mild cognitive impairment (aMCI) were included in this analysis. Population-averaged decline to dementia rates was estimated and compared for standardized MMSE, CDR-SB, and CS using Generalized Estimating Equations (GEE). Associations between rate of decline and several potential correlates of decline were also calculated and compared across measures. Results: The CDR-SB had the steepest estimated slope, with a decline of 0.49 standard deviations (SD) per year, followed by the MMSE with 0.22 SD per year, and finally the CS with 0.07 SD per year. The rate of decline of the three measures differed significantly in a global test for differences (p < 0.0001). Age at visit, body mass index (BMI) at visit, Apolipoprotein E (APOE) ?4 allele status, and race (black vs. white) had significantly different relationships with rate of decline in a global test for difference among the three measures. Conclusions: These results suggest that both the rate of decline and the effects of AD risk factors on decline to dementia can vary depending on the evaluative measure used.     

Interaction between vascular factors and the APOE ε4 allele in predicting rate of progression in Alzheimer's disease

Vascular factors have been shown to affect the rate of Alzheimer's disease (AD) progression. However, the effect of the APOE ε4 allele on rate of progression has been ambiguous. Little research to date has examined an interaction between vascular factors and the APOE ε4 allele in predicting decline among AD patients. 216 participants with incident AD from a population of elderly persons in Cache County, Utah, were followed for a mean of 3.3 years and 4.2 follow-up visits. A history of vascular risk factors and conditions and anti-hypertensive use was assessed at the diagnostic visit. Linear mixed effects models tested interactions between the vascular factors, APOE ε4, and time as predictors of clinical progression on the Mini-Mental State Exam (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB). Multiple comparisons were corrected using the Holm-Bonferroni method. There was a 3-way interaction between stroke, APOE ε4 and time in predicting MMSE decline (LR χ2 = 10.32, 2 df, p = 0.006). For the CDR-SB, there were 3-way interactions between the APOE ε4, time and either myocardial infarction (LR χ2 = 17.83, 2 df, p = 0.0001) or stroke (LR χ2 = 11.48, 2 df, p = 0.003. Results suggest a complex relationship between the APOE ε4 and vascular factors in predicting cognitive and functional progression. Among individuals with a history of stroke or myocardial infarction at baseline, progression of AD is influenced by APOE ε4 carrier status and varies by time after AD diagnosis.     

Is functional decline necessary for a diagnosis of Alzheimer's disease?

BACKGROUND: The purpose of this study is to examine baseline differences and annualized cognitive and functional change scores in mild Alzheimer's disease (AD) patients with and without impaired activities of daily living (ADL). METHODS: We recruited 267 mild probable AD patients with at least 1 year of follow-up (NINCDS-ADRDA criteria, MMSE>or=20). Based on initial ADL scores, they were divided into 2 groups: unimpaired (n=40) and impaired (n=227). We compared the differences in annualized change scores on MMSE, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), ADL and Clinical Dementia Rating sum of box score (CDR-SB) for patients with and without functional impairment at baseline. RESULTS: The group with unimpaired ADL at baseline had a significantly shorter symptom duration (p=0.01) and better neuropsychological test scores at baseline (p<0.001) than those with impaired ADL. The annualized cognitive and functional change of each group from baseline to 1-year follow-up was not significantly different on the MMSE, ADAS-cog, CDR-SB, Physical Self-Maintenance Scale and Instrumental Activities of Daily Living. After 1 year, 56% of the initially unimpaired group and 6% of the initially impaired group reported no ADL impairment. CONCLUSIONS: Our study suggests that functional decline should not be required for the diagnosis of mild AD.     

The value of the clock drawing test and the mini-mental state examination for identifying vascular cognitive impairment no dementia

OBJECTIVE: To determine the validity of the Clock Drawing Test (CDT) and the Mini-Mental State Examination (MMSE) respectively or in combination for differentiating Vascular Cognitive Impairment No Dementia (V-CIND) from normal subjects. METHODS: Eighty V-CIND patients and 80 healthy control subjects were blindly evaluated with MMSE, CDT, and additional neuropsychological tests. CDT was scored according to the Rouleau method and AD Cooperative Study method. Sensitivities and specificities of the two CDT measures and MMSE for identifying V-CIND patients were determined. The Areas Under the Receiver Operating Characteristic Curve (AUCs) were compared, and the sensitivity of the combination of CDT with MMSE calculated. RESULTS: V-CIND group performed worse than controls on both MMSE (p < 0.0001) and the two CDTs (p < 0.0001). In differentiating V-CIND patients from normal subjects, the two CDT measures provided sensitivities of 68.7% and 65.0%, and specificities of 78.7% and 86.2% respectively at optimal cutoff scores, which did no better than MMSE (sensitivity 80%, specificity 70%) (comparison of the AUCs, p = 0.992 and 0.428). The sensitivity of MMSE was marginally higher than that of CDT scored with AD Cooperative Study method (p = 0.053). By combining the two CDT measures with MMSE, the sensitivity was improved to 93.7% and 92.5% respectively. CONCLUSIONS: Compared with MMSE, CDT is of only similar or even weaker ability for identifying V-CIND. MMSE at a cutoff of 28 may be of some value in detecting V-CIND patients. CDT and MMSE in combination provide a valid instrument for V-CIND screening.     

Cases with mild cognitive impairment and Alzheimer's disease fail to benefit from repeated exposure to episodic memory tests as compared with controls

Memory tests may be predictive for cognitive decline. We investigated the sensitivity and change in performance over time of the Hopkins Verbal Learning Test (HVLT) and the Mini-Mental Status Examination (MMSE) for Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) when compared to cognitively healthy controls.Participants included elderly controls (n = 54), MCI (n = 19) and AD cases (n = 28) from OPTIMA. The MMSE and the HVLT (version 1) were administered twice to all subjects with an interval of 2-3 years.MCI and AD cases had poorer performance than controls on the HVLT and MMSE at both testing episodes (p < 0.05). The HVLT profile over time showed a learning effect in the control group (P < 0.0001), a trend to decline in the AD group (p = 0.09) and no change in the MCI group (P = 0.8). A subgroup of MCI subjects had lower HVLT scores at follow-up. The MMSE profile showed no significant change over time for all three groups (P > 0.05). The HVLT had better sensitivity and specificity compared to the MMSE for detecting MCI and AD.The HVLT is not only valuable for cross-sectional designs but has also proved to be valuable in a longitudinal design. Cognitively healthy controls showed evidence of learning strategies on the HVLT after a 2-3 year interval, with improved scores at the second testing episode. By contrast, an MCI group showed no benefits of previous exposure to this test. Lack of use of learning strategies on the HVLT may be an important marker of the likelihood of cognitive decline to MCI or dementia.     

Stage-dependent BDNF serum concentrations in Alzheimer’s disease

Summary. Alzheimer’s disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores ≥21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3). As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls. In summary, BDNF serum values are increased in early stages of Alzheimer’s disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer’s disease.     

Peripheral oxidative stress biomarkers in mild cognitive impairment and Alzheimer's disease

Oxidative stress has been associated with normal aging and Alzheimer's disease (AD). However, little is known about oxidative stress in mild cognitive impairment (MCI) patients who present a high risk for developing AD. The aim of this study was to investigate plasma production of the lipid peroxidation marker, malonaldehyde (MDA) and to determine, in erythrocytes, the enzymatic antioxidant activity of catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) in 33 individuals with MCI, 29 with mild probable AD and 26 healthy aged subjects. GR/GPx activity ratio was calculated to better assess antioxidant defenses. The relationship between oxidative stress and cognitive performance was also evaluated by the Mini Mental State Examination (MMSE). AD patients showed higher MDA levels than both MCI and healthy elderly subjects. MCI subjects also exhibited higher MDA levels compared to controls. Catalase and GPx activity were similar in MCI and healthy individuals but higher in AD. GR activity was lower in MCI and AD patients than in healthy aged subjects. Additionally, GR/GPx ratio was higher in healthy aged subjects, intermediate in MCI and lower in AD patients. No differences in GST activity were detected among the groups. MMSE was negatively associated with MDA levels (r = -0.31, p = 0.028) and positively correlated with GR/GPx ratio in AD patients (r = 0.68, p < 0.001). MDA levels were also negatively correlated to GR/GPx ratio (r = -0.31, p = 0.029) in the AD group. These results suggest that high lipid peroxidation and decreased antioxidant defenses may be present early in cognitive disorders.     

Plasma concentration of donepezil to the therapeutic response of Alzheimer's disease in Taiwanese

Donepezil has been approved for the treatment for mild-to-moderate Alzheimer's disease (AD), but the therapeutic response rate varies from 20 to 60%. A higher oral dosage was suggested to have a better therapeutic response in reported results, but the plasma concentration of donepezil was not examined with respect to the therapeutic outcomes in those studies. Therefore, we analyzed the therapeutic responses, measured by neuropsychological assessments, among 70 newly diagnosed AD patients taking donepezil (5 mg daily) in relation to their plasma concentration of donepezil, apolipoprotein E genotype, and demographic characteristics. Our results have showed 60% of recruited AD patients improved in cognition, measured by Mini-Mental Status Examination (MMSE), and 57.1% in global status, by Clinical Dementia Rating Scale (CDR) sum of boxes (CDR-SB). In cognition, compared to the improving group, the clinically worsening group had a significantly higher donepezil concentration [p = 0.022, odds ratio (OR) = 1.024, 95% CI = 1.003-1.045] and higher initial MMSE score (p = 0.007, OR = 1.330, 95% CI = 1.080-1.639). In global status, initially higher CDR-SB (p = 0.028, OR = 2.318, 95% CI = 1.096-4.903) and initially higher MMSE (p = 0.036, OR = 1.201, 95% CI = 1.012-1.425), not donepezil concentration (p = 0.883), were significantly associated with clinical worsening. Our results have indicated that the dosage of donepezil should be reconsidered for AD patients, especially those clinically worsening in cognition.     

阿尔茨海默病患者血浆脂联素与Aβ水平的变化

目的 探讨AD患者血浆脂联素、Aβ水平的变化及其与MMSE评分的关系。方法 对20例AD患者(AD组)、20例正常认知老年组的血浆脂联素、Aβ40和Aβ42水平进行检测,比较2组血浆脂联素和Aβ水平的差异,并分析血浆脂联素、Aβ与MMSE评分的关系。结果 AD组MMSE评分、血浆脂联素(APN)、Aβ42和Aβ42/Aβ40均低于对照组(P<0.05)。Aβ40水平与Aβ42水平呈显著正相关、与Aβ42/Aβ40呈显著负相关(P<0.01),Aβ42水平与APN水平呈显著正相关(P<0.05),MMSE评分与Aβ42、APN、Aβ42/Aβ40呈显著正相关(P<0.01)。结论 AD组血浆APN、Aβ42水平和Aβ42/Aβ40明显降低,其改变与认知功能评分存在一定的正相关性。     

血清S100B蛋白抗脑抗体海马体积变化与阿尔茨海默病患者认知功能变化的关系

目的探讨血清S100B蛋白、抗脑抗体(ABAb)、海马体积大小变化与阿尔茨海默病(AD)患者认知功能变化的关系。方法选取濮阳市油田总医院确诊的88例阿尔茨海默病患者(AD组),选取正常体检者90例为对照组,检测并对比2组血清S100B蛋白、ABAb、海马体积,采用线性相关、多元线性回归分析各项研究指标与简易精神状态量表(MMSE)的相关性。结果AD组血清S100B蛋白、ABAb测定值均高于对照组(P<0.05);AD组海马体积、MMSE评分均低于对照组(P<0.05);AD组血清S100B蛋白、ABAb测定值与MMSE评分呈负相关性(P<0.05);AD组海马体积与MMSE评分呈正相关性(P<0.05);多元线性回归模型显示,血清S100B蛋白、ABAb增高与AD患者MMSE评分呈负相关(P<0.05),海马体积、受教育年限与MMSE评分呈正相关(P<0.05)。结论AD患者的血清S100B蛋白、ABAb增高,海马体积较健康人群降低,且与患者认知功能受损程度有关。     

The Short Cognitive Performance Test (SKT): a preliminary study of its psychometric properties in Brazil

BACKGROUND: Most instruments designed to detect dementia can lack appropriate sensitivity in the early stages of Alzheimer's disease (AD), and are subject to educational bias. The Short Cognitive Performance Test (Syndrom-Kurztest, SKT) is considered a suitable instrument to measure cognitive decline as it assesses memory, attention, and related cognitive functions, taking into account the speed of information processing. OBJECTIVES: The aim of this study was to examine the psychometric characteristics of the SKT as a dementia screening instrument in a Brazilian population sample, as compared to the Mini-mental State Examination (MMSE) and the Clock-Drawing Test (CDT). The effect of educational level on performance in the three screening tests was also verified. METHODS: Fifty-one elderly subjects were assessed. Consensus diagnoses were established by an expert multidisciplinary team, considering clinical, neuropsychological and neuroimaging data. Subjects were further classified into those with (1) mild and moderate AD, (2) non-Alzheimer's dementia, (3) mild cognitive impairment, and (4) controls, according to National Institute for Communicative Disorders and Stroke--Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. RESULTS: Statistical analyses revealed high internal consistency for the SKT (Cronbach's alpha = 0.80) and significant correlations between the total score and the SKT subscores separately (p < 0.01). Comparison of the three tests revealed strong correlations between the SKT and the MMSE (r = -0.66, p < 0.0001) and between the SKT and the CDT (r = -0.57, p < 0.0001). The SKT, MMSE and CDT scores were correlated with education. CONCLUSIONS: The Brazilian version of the SKT maintains its original psychometric properties and displays significant correlation with previously validated screening tools for dementia. Like other dementia screening tests, the SKT is subject to educational bias.     

Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?

Plasma concentrations of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), C reactive protein (CRP) and alpha-1-antichymotrypsin (ACT) in 145 patients with probable Alzheimer's disease (AD) and 51 non-demented controls were measured. To investigate the cellular activation of peripheral immune system, plasma levels of neopterin were also investigated. Plasma levels of IL-1 were detectable in 17 patients with AD (13%) and only in one control (2%) and average levels of IL-1 were higher in AD patients than in controls (p < 0.001). IL-6 plasma levels were detectable in a higher proportion of AD and controls (53% and 27%, respectively), and were increased in patients with AD (p < 0.001). Plasma levels of ACT were increased in patients with AD (p < 0.001) and CRP levels were in the normal range. Plasma levels of neopterin were slightly lower in AD patients than in controls, but differences were not statistically significant. No significant correlation was observed between IL-1 and IL-6 levels or neopterin and cytokine levels in plasma from AD patients. Plasma levels of ACT negatively correlated with cognitive performances, as assessed by the mini mental state examination (MMSE; R = -0.26, p < 0.02) and positively correlated with the global deterioration state (GDS) of AD patients (R = 0.30, p < 0.007). Present findings suggested that detectable levels of circulating cytokines and increased ACT might not be derived by activation of peripheral immune system of AD patients. Detection of these molecules might be used for monitoring the progression of brain inflammation associated with AD.     

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.

     

Correlation between disease severity and brain electric LORETA tomography in Alzheimer's disease.

OBJECTIVE: To compare EEG power spectra and LORETA-computed intracortical activity between Alzheimer's disease (AD) patients and healthy controls, and to correlate the results with cognitive performance in the AD group. METHODS: Nineteen channel resting EEG was recorded in 21 mild to moderate AD patients and in 23 controls. Power spectra and intracortical LORETA tomography were computed in seven frequency bands and compared between groups. In the AD patients, the EEG results were correlated with cognitive performance (Mini Mental State Examination, MMSE). RESULTS: AD patients showed increased power in EEG delta and theta frequency bands, and decreased power in alpha2, beta1, beta2 and beta3. LORETA specified that increases and decreases of power affected different cortical areas while largely sparing prefrontal cortex. Delta power correlated negatively and alpha1 power positively with the AD patients' MMSE scores; LORETA tomography localized these correlations in left temporo-parietal cortex. CONCLUSIONS: The non-invasive EEG method of LORETA localized pathological cortical activity in our mild to moderate AD patients in agreement with the literature, and yielded striking correlations between EEG delta and alpha1 activity and MMSE scores in left temporo-parietal cortex. SIGNIFICANCE: The present data support the hypothesis of an asymmetrical progression of the Alzheimer's disease.     

Early onset Alzheimer's disease is associated with a distinct neuropsychological profile

Alzheimer's disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuo-spatial functioning, executive functioning, attention). Dementia severity was assessed using the Mini-Mental State Examination (MMSE) and global cognitive decline using Cambridge Cognitive Examination (CAMCOG). Analyses of variance were performed with age-at-onset as between-subjects factor, and gender and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean ± SD) was 60 ± 4 years; 44 (54%) were female. In late onset AD, age was 72 ± 5 years; 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20 ± 5, CAMCOG: 69 ± 15, late onset: MMSE: 21 ± 5, CAMCOG: 70 ± 15; p > 0.05). Early onset patients performed worse than late onset patients on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuo-spatial functioning (p < 0.01), executive functioning (p < 0.001), and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems different. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.     

Differences in cortical thickness in healthy controls, subjects with mild cognitive impairment, and Alzheimer's disease patients: a longitudinal study

In this study, we analyzed differences in cortical thickness (CTH) between healthy controls (HC), subjects with stable mild cognitive impairment (S-MCI), progressive MCI (P-MCI), and Alzheimer's disease (AD), and assessed correlations between CHT and clinical disease severity, education, and apolipoprotein E4 (APOE) genotype. Automated CTH analysis was applied to baseline high-resolution structural MR images of 145 subjects with a maximum followup time of 7.4 years pooled from population-based study databases held in the University of Kuopio. Statistical differences in CTH between study groups and significant correlations between CTH and clinical and demographic factors were assessed and displayed on a cortical surface model. Compared to HC group (n = 26), the AD (n = 21) group displayed significantly reduced CTH in several areas of frontal and temporal cortices of the right hemisphere. Higher education and lower MMSE scores were correlated with reduced CTH in the AD group, whereas no significant correlation was found between CDR-SB scores or APOE genotype and CTH. The P-MCI group demonstrated significantly reduced CTH compared to S-MCI in frontal, temporal and parietal cortices even after statistically adjusting for all confounding variables. Ultimately, analysis of CTH can be used to detect cortical thinning in subjects with progressive MCI several years before conversion and clinical diagnosis of AD dementia, irrespective of their cognitive performance, education level, or APOE genotype.     

Use of an Italian version of the telephone interview for cognitive status in Alzheimer's disease

OBJECTIVES: Validation of an Italian version of the Telephone Interview for Cognitive Status (I-TICS). METHODS: Telephone administration of the I-TICS within 6 weeks of face-to-face testing with the Mini Mental State Examination (MMSE), in Probable Alzheimer's disease (AD) patients and healthy controls. Two hundred and seven consecutive outpatients with cognitive impairment were recruited from Dementia Clinic of University Campus BioMedico. Of these, 45 probable AD patients with complete data were analyzed. Other dementias, Mild Cognitive Impairment (MCI), and patients with incomplete data were excluded. The control sample consisted of 64 age- and sex-matched healthy subjects. For diagnosis, an extensive clinical evaluation, laboratory testing, brain imaging, EEG, neuropsychological battery and a depression scale were used. For I-TICS validation, telephone I-TICS and face-to-face MMSE were administered. RESULTS: The I-TICS correlated highly and linearly with the MMSE (Pearson's r=0.904). Conversion equations are provided. Sensitivity and specificity were similar between tests (area under curve=0.894 for the I-TICS; 0.966 for the MMSE). I-TICS sensitivity was 84% and specificity 86% at a cut-off score of 28. No significant difference in accuracy with the MMSE was present. Total agreement between I-TICS and MMSE was 'substantial' at 86% (Cohen's K=0.717). Repeated testing in a subset of patients showed a disease progression related decrease of 4.2 points/year (t=2.664; p=0.018) in I-TICS scores. CONCLUSION: The I-TICS is a valid instrument in clinical and research screening and monitoring of AD. Potential applications in other dementias and MCI are worth further studies.     

Cerebral serotonin 4 receptors and amyloid-β in early Alzheimer's disease

The 5-HT4 receptor may play a role in memory and learning and 5-HT4 receptor activation has been suggested to modulate acetylcholine release and to reduce amyloid-β (Aβ) accumulation. The aim of this study was for the first time to investigate the in vivo cerebral 5-HT4 receptor binding in early Alzheimer disease (AD) patients in relation to cortical Aβ burden. Eleven newly diagnosed untreated AD patients (mean MMSE 24, range 19-27) and twelve age- and gender-matched healthy controls underwent a two-hour dynamic [11C]SB207145 PET scan to measure the binding potential of the 5-HT4 receptor. All AD patients and eight healthy controls additionally underwent a [11C]PIB PET scan to measure the cortical Aβ burden. When AD patients were defined on clinical criteria, no difference in cerebral 5-HT4 receptor binding between AD patients and healthy controls was found (p = 0.54). However, when individuals were reassigned to groups according to their amyloid status, the PIB-positive individuals had 13% higher 5-HT4 receptor levels than PIB-negative individuals (p = 0.02) and the importance of classification of groups is emphasized. The 5-HT4 receptor binding was a positively correlated to Aβ burden (p = 0.03) and negatively to MMSE score of the AD patients (p = 0.02). Our data suggests that cerebral 5-HT4 receptor upregulation starts at a preclinical stage of and continues while dementia is still at a mild stage, which contrasts other receptor subtypes. We speculate that this may either be a compensatory effect of decreased levels of interstitial 5-HT, an attempt to improve cognitive function, increase acetylcholine release or to counteract Aβ accumulation.