Mild AD Group Research Articles

Language impairments in Alzheimer´s disease: What changes can be found between mild and moderate stages of the disease?

ObjectiveTo investigate how language deteriorates over the Alzheimer's Disease course. MethodsA cross-sectional, observational study was carried out. 35 patients diagnosed with dementia due to AD using the NINCDS-ARDRA criteria and undergoing treatment for AD with a therapeutic dose of acetylcholinesterase inhibitors were assessed by the Boston Diagnostic Aphasia Examination (BDAE). The sample comprised 15 patients with mild AD (MMSE > 23, CDR = 0 or 0.5‒1.0) and 20 patients with moderate AD (MMSE = 13‒23, CDR = 2). The results for the 2 groups on all language tasks were compared. ResultsA statistically significant difference was found between the mild and moderate AD groups for total score on the BDAE (95% CI 47.10‒114.08, t = 5.0, DF = 21, p = 0.000*), as well as on several tasks involving oral and writing comprehension, language oral expression and writing. ConclusionThe study results showed major changes in the moderate stage. Also, the decline in language performance correlated with the worsening of dementia syndrome, independently of sociodemographic variables.

Correlation of serum complement factor 5a level with inflammatory response and cognitive function in patients with Alzheimer’s disease of different severity

BackgroundAlzheimer’s disease (AD) is a common cause of dementia. Serum complement factor 5a (C5a) is exceedingly implicated in AD. We explored the role of C5a levels in AD patients of different severity.MethodsMild, moderate, and severe AD patients, and healthy controls were included. C5a and pro-inflammatory factor (TNF-α, IL-1β, IL-6, CRP) levels were assessed by ELISA, and cognitive function was evaluated by Mini-Mental state examination (MMSE) score. The correlations between C5a, inflammatory factor levels, MMSE score, and plasma Aβ42/Aβ40 ratio were analyzed by Pearson tests. Independent risk factors for AD aggravation were assessed by logistic multivariate regression analysis. According to the cut-off value of receiver operating characteristic (ROC) curve analysis of C5a level, AD patients were assigned into low/high expression groups, and severe AD incidence was compared. Severe AD cumulative incidence was analyzed by Kaplan-Meier curve.ResultsSerum C5a, TNF-α, IL-1β, IL-6 and CRP levels were raised, and MMSE score was lowered in AD. Serum C5a, TNF-α, IL-1β, IL-6 and CRP levels in severe AD patients were higher than those in mild/moderate AD patients, but there were no significant differences in these cytokines between moderate and mild AD groups. The MMSE score of severe AD patients was lower than that of mild/moderate AD patients. Serum C5a level was positively correlated with serum TNF-α, IL-1β, IL-6, and CRP levels, and negatively correlated with MMSE score, with no obvious correlation with plasma Aβ42/Aβ40 ratio. Serum C5a level was one of the independent risk factors for AD aggravation. The occurrence of severe AD might be related to an increase in serum C5a level.ConclusionSerum C5a level increased with AD severity, and its expression was positively correlated with serum pro-inflammatory factor levels, and negatively correlated with cognitive function.

Effect of Paediatric Atopic Dermatitis on Parental Sleep Quality.

Data on the impact of paediatric atopic dermatitis on parental sleep are scarce. The aim of this study was to examine the effects of paediatric atopic dermatitis on the quality of parents' sleep. This cross-sectional study included parents of patients with atopic dermatitis and parents of healthy children who completed validated Pittsburgh Sleep Quality Index questionnaires. The study and control groups were compared, as were results for mild and moderate atopic dermatitis with severe atopic dermatitis, mothers and fathers, and different ethnic groups. A total of 200 parents were enrolled. Sleep latency was significantly longer in the study group compared with the control group. Sleep duration was shorter in the parents of the mild AD group compared with the moderate-severe and control groups. Parents in the control group reported more daytime dysfunction than parents in the AD group. Fathers of children with AD reported more sleep disturbance than mothers.

Gait Indicators Contribute to Screening Cognitive Impairment: A Single- and Dual-Task Gait Study.

Screening cognitive impairment is complex and not an appliance for early screening. Gait performance is strongly associated with cognitive impairment. We aimed to explore gait indicators that could potentially screen cognitive dysfunction. A total of 235 subjects were recruited from June 2021 to June 2022. Four gait tasks, including the walking test, the timed "Up & Go" test (TUG), foot pressure balance (FPB), and one-legged standing with eyes closed test (OLS-EC), were performed. Moreover, in the walking test, participants were instructed to walk at their usual pace for the single-gait test. For the dual-task tests, participants walked at their usual pace while counting backward from 100 by 1s. The data were analyzed by the independent sample t-test, univariate and multivariate logistic regression, a linear trend, stratified and interaction analysis, the receiver operating characteristic (ROC) curve, and Pearson's correlations. Among the 235 participants, 81 (34.5%) were men and 154 (65.5%) were women. The mean age of participants was 72 ± 7.836 years. The control, MCI, mild AD, and severe AD groups had means of 71, 63, 71, and 30, respectively. After adjusting for age, sex, education, and body mass index (BMI), the dual-task toe-off-ground angle (TOA) (odds ratio (OR) = 0.911, 95% confidence interval (CI): 0.847, 0.979), single-task TOA (OR = 0.904, 95% CI: 0.841-0.971), and the timed "Up & Go" time (TUGT) (OR = 1.515, 95% CI: 1.243-1.846) were significantly associated with an increased risk of cognitive impairment. In addition, the trend test and stratified analysis results had no significant differences (all p > 0.05). The area under the roc curve (AUC) values of TOA in the dual-task and TUGT were 0.812 and 0.847, respectively. Additionally, TOA < 36.75° in the dual-task, TOA < 38.90° in the single-task, and TUGT > 9.83 seconds (s) are likely to indicate cognitive impairment. The cognitive assessment scale scores were significantly correlated with TOA (all r > 0.3, p < 0.001) and TUGT (all r > 0.2), respectively. TOA and TUGT scores are, in some circumstances, associated with cognitive impairment; therefore, they can be used as simple initial screenings to identify patients at risk.

Reproducibility of isokinetic measures of the knee and ankle muscle strength in community-dwelling older adults without and with Alzheimer’s disease

BackgroundTo interpret changes of muscle strength in older adults with Alzheimer’s disease (AD), determining the reliability of outcome measures is necessary. Therefore, the purpose of the present study was to investigate the relative and absolute intra-rater reliability of concentric isokinetic measures of the knee and ankle muscle strength in community-dwelling older adults without and with AD in the mild and moderate stages.MethodsA methodological study was conducted. The participants were submitted to two isokinetic evaluations with an interval of three to seven days. The evaluations consisted of knee extension and flexion at 60°/s (five repetitions) and 180°/s (15 repetitions) and plantar flexion and dorsiflexion of the ankle at 30°/s (five repetitions). The measures of interest were peak torque, average peak torque and total work. The intraclass correlation coefficient two-way mixed model of a single-measure (ICC3,1), standard error of measurement (SEM) and minimal detectable change at the 95% confidence interval (MDC95) were calculated. The ICC3,1 was interpreted based on Munro’s classification. Standard error of measurement and MDC95 were analyzed in absolute and relative values (percentage of error [SEM%] and change [MDC95%]).ResultsA total of 62 older adults were included and allocated to the three groups: mild-AD (n = 22, 79.9 years, 15 female and seven male), moderate-AD (n = 20, 81.6 years, 15 female and five male) and without-AD (n = 20, 74.3 years, 10 female and seven male). The ICCs3,1 of the measures of knee were high/very high in the three groups (0.71–0.98). The ICCs3,1 of the measures of ankle were high/very high in the mild-AD group (0.78–0.92), moderate/high/very high in the moderate-AD group (0.63–0.93) and high/very high in the group without-AD (0.84–0.97). The measurements of knee extensors at 60°/s, knee extensors (peak torque and total work), with the exception of peak torque in the mild-AD group, and flexors (average peak torque) at 180°/s, and ankle dorsiflexors at 30°/s had the lowest of SEM% and MDC95% in the three groups.ConclusionConcentric isokinetic measures are reliable for the assessment of knee and ankle muscle strength in community-dwelling older adults without and with AD in the mild and moderate stages.

Validation of a digit symbol substitution test for use in supervised and unsupervised assessment in mild Alzheimer’s disease

ABSTRACT Introduction The Digit-Symbol-Substitution Test (DSST) is used widely in neuropsychological investigations of Alzheimer’s Disease (AD). A computerized version of this paradigm, the DSST-Meds, utilizes medicine-date pairings and has been developed for administration in both supervised and unsupervised environments. This study determined the utility and validity of the DSST-Meds for measuring cognitive dysfunction in early AD. Method Performance on the DSST-Meds was compared to performance on the WAIS Coding test, and a computerized digit symbol coding test (DSST-Symbols). The first study compared supervised performance on the three DSSTs versions in cognitively unimpaired (CU) adults (n = 104). The second compared supervised DSST performance between CU (n = 60) and mild-symptomatic AD (mild-AD, n = 79) groups. The third study compared performance on the DSST-Meds between unsupervised (n= 621) and supervised settings. Results In Study 1, DSST-Meds accuracy showed high correlations with the DSST-Symbols accuracy (r = 0.81) and WAIS-Coding accuracy (r = 0.68). In Study 2, when compared to CU adults, the mild-AD group showed lower accuracy on all three DSSTs (Cohen’s d ranging between 1.39 and 2.56) and DSST-Meds accuracy was correlated moderately with Mini-Mental State Examination scores (r = 0.44, p < .001). Study 3 observed no difference in DSST-meds accuracy between supervised and unsupervised administrations. Conclusion The DSST-Meds showed good construct and criterion validity when used in both supervised and unsupervised contexts and provided a strong foundation to investigate the utility of the DSST in groups with low familiarity to neuropsychological assessment.

A comparison of the composition and functions of the oral and gut microbiotas in Alzheimer's patients.

ObjectiveAlterations in the oral or gut microbiotas have been reported in patients with subjective and mild cognitive impairment or AD dementia. However, whether these microbiotas change with the severity of the AD spectrum (mild, moderate, and severe AD) remains unknown. Thus, we compared alterations in the composition and gene functions of the oral and gut microbiota between different phases of AD.MethodsWe recruited 172 individuals and classified these into three groups: healthy controls (n = 40), a mild AD group (n = 43) and a moderate AD group (n = 89). Subgingival plaques and fecal samples were collected from all individuals. Then, we conducted 16S ribosomal RNA. sequencing to analyze the microbiotas.ResultsIn order of the severity of cognition impairment (from normal to mild and to moderate AD), the oral abundances of the phyla Firmicutes and Fusobacteria showed a gradual upwards trend, while the abundance of the Proteobacteria phylum gradually decreased. In contrast, the abundance of the Firmicutes and Bacteroidetes phyla in the gut decreased progressively, while that of the Proteobacteria, Verrucomicrobia and Actinobacteria phyla increased gradually. Key differences were identified in the microbiomes when compared between the mild AD and moderate AD groups when applying the linear discriminant analysis effect size (LEfSe) algorithm. LEfSe analysis revealed alterations that were similar to those described above; furthermore, different bacterial taxa were associated with MMSE scores and age. KEGG analysis showed that the functional pathways associated with the oral microbiota were mainly involved in membrane transport and carbohydrate metabolism, while the gene functions of the fecal microbiota related to metabolism of amino acids, energy, cofactors and vitamins; identified significant differences among the three groups. Venn diagram analysis revealed that the number of genera that were present in both the oral and gut microbiota increased progressively from NC to mild AD and then to moderate AD.ConclusionsThis study is the first to report a comparative analysis of the oral and fecal microbiota of patients with mild and moderate AD. The compositions and functions of the oral and gut microbiotas differed when compared between different stages of AD.

Breaking the flow of thought: Increase of empty pauses in the connected speech of people with mild and moderate Alzheimer's disease

IntroductionThe profile of spontaneous speech in Alzheimer's disease (AD) includes increased pausing as a window into cognitive decline. We here aimed to further characterize the pausing profile of AD by linking pauses to the syntactic positions in which they appear and disease progression. MethodsSpeech was obtained through a picture description task, thus minimizing demands on episodic memory (EM), from a group of mild (N = 21) and moderate AD (N = 19), and healthy elderly controls (N = 40). Pauses were sub-indexed according to whether they occurred within-clauses, clause-initially, or utterance-initially, and whether they preceded nouns, verbs, or adjectives/adverbs, when occurring within-clauses. Additionally, relations to verbal fluency (VF) measures at the single-word level were explored. ResultsPause rate but not duration distinguished controls from both AD groups, while fillers did not distinguish any groups. The analysis by syntactic position revealed a highly differentiated picture, with largest effect sizes of significant group differences seen in the utterance-initial pause rate. The two AD groups patterned differently when compared to controls, while none of the measures differentiated the AD groups. Specifically, moderate but not mild AD differed from controls in clause-initial pauses, while mild but not moderate AD differed from controls in within-clause positions. At the within-clause level, the effect dividing controls from mild-AD was specifically driven by pauses ahead of nouns. A significant negative correlation emerged between pausing rate in spontaneous speech and VF measures in the mild-AD group only. ConclusionsIncreased empty (non-filled) pauses in AD are not confined to pauses in within-clause positions, which are most directly related to problems in the retrieval of words. Even in early disease stages, where these within-clause pause effects are seen, they are confined to nouns, revealing a grammatically specific problem possibly related to the referencing of objects. At all disease stages, pauses increase in utterance-sized units of structure, indicating progressive problems in the creative configuration of complete thoughts.

The Smart Aging Platform for Assessing Early Phases of Cognitive Impairment in Patients With Neurodegenerative Diseases.

Background: Smart Aging is a serious game (SG) platform that generates a 3D virtual reality environment in which users perform a set of screening tasks designed to allow evaluation of global cognition. Each task replicates activities of daily living performed in a familiar environment. The main goal of the present study was to ascertain whether Smart Aging could differentiate between different types and levels of cognitive impairment in patients with neurodegenerative disease.Methods: Ninety-one subjects (mean age = 70.29 ± 7.70 years)—healthy older adults (HCs, n = 23), patients with single-domain amnesic mild cognitive impairment (aMCI, n = 23), patients with single-domain executive Parkinson's disease MCI (PD-MCI, n = 20), and patients with mild Alzheimer's disease (mild AD, n = 25)—were enrolled in the study. All participants underwent cognitive evaluations performed using both traditional neuropsychological assessment tools, including the Mini-Mental State Examination (MMSE), Montreal Overall Cognitive Assessment (MoCA), and the Smart Aging platform. We analyzed global scores on Smart Aging indices (i.e., accuracy, time, distance) as well as the Smart Aging total score, looking for differences between the four groups.Results: The findings revealed significant between-group differences in all the Smart Aging indices: accuracy (p < 0.001), time (p < 0.001), distance (p < 0.001), and total Smart Aging score (p < 0.001). The HCs outperformed the mild AD, aMCI, and PD-MCI patients in terms of accuracy, time, distance, and Smart Aging total score. In addition, the mild AD group was outperformed both by the HCs and by the aMCI and PD-MCI patients on accuracy and distance. No significant differences were found between aMCI and PD-MCI patients. Finally, the Smart Aging scores significantly correlated with the results of the neuropsychological assessments used.Conclusion: These findings, although preliminary due to the small sample size, suggest the validity of Smart Aging as a screening tool for the detection of cognitive impairment in patients with neurodegenerative diseases.

Serum Tau Proteins as Potential Biomarkers for the Assessment of Alzheimer's Disease Progression.

Total tau (t-tau) and phosphorylated tau (p-tau) protein elevations in cerebrospinal fluid (CFS) are well-established hallmarks of Alzheimer’s disease (AD), while the associations of serum t-tau and p-tau levels with AD have been inconsistent across studies. To identify more accessible non-invasive AD biomarkers, we measured serum tau proteins and associations with cognitive function in age-matched controls (AMC, n = 26), mild cognitive impairment group (MCI, n = 30), and mild-AD group (n = 20) according to the Mini-mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Global Deterioration Scale (GDS) scores. Serum t-tau, but not p-tau, was significantly higher in the mild-AD group than AMC subjects (p < 0.05), and there were significant correlations of serum t-tau with MMSE and GDS scores. Receiver operating characteristic (ROC) analysis distinguished mild-AD from AMC subjects with moderate sensitivity and specificity (AUC = 0.675). We speculated that tau proteins in neuronal cell-derived exosomes (NEX) isolated from serum would be more strongly associated with brain tau levels and disease characteristics, as these exosomes can penetrate the blood-brain barrier. Indeed, ELISA and Western blotting indicated that both NEX t-tau and p-tau (S202) were significantly higher in the mild-AD group compared to AMC (p < 0.05) and MCI groups (p < 0.01). In contrast, serum amyloid β (Aβ1–42) was lower in the mild-AD group compared to MCI groups (p < 0.001). During the 4-year follow-up, NEX t-tau and p-tau (S202) levels were correlated with the changes in GDS and MMSE scores. In JNPL3 transgenic (Tg) mice expressing a human tau mutation, t-tau and p-tau expression levels in NEX increased with neuropathological progression, and NEX tau was correlated with tau in brain tissue exosomes (tEX), suggesting that tau proteins reach the circulation via exosomes. Taken together, our data suggest that serum tau proteins, especially NEX tau proteins, are useful biomarkers for monitoring AD progression.

The evaluation of thiol-disulfıte balance, ischemıa albumın modıfıcation and seruloplazmine as a new oxidatıve stress in mild cognitive impairment and early stage alzheimer’s disease patients

BackgroundAlzheimer's Disease (AD) is the most common form of dementia seen in advanced age. It is characterized by progressive deterioration in cognitive functions. The prevalence of Alzheimer's disease increasing day by day due to the increase in the share of the elderly population in the general population due to developing health and living conditions, is limited and early diagnosis and effective treatment possibilities are very limited. From this point of view, a specific biomarker for AD is very important. As a new oxidative stress biomarker, the levels of thiol-disulfide balance, ischemia-modified albumin and seroloplazminin were evaluated. The aim of this study was to determine the serum levels of oxidative stress biomarkers in the early stages of the disease and to compare these oxidative stress markers with patients with mild cognitive impairment as a precursor form of Alzheimer's disease and to determine whether these markers develop at an earlier stage. Methods30 volunteers with early stage AD according to NINCDS-ARDRA criteria, 19 volunteers with Midl Cognitive İmpairment according to PCA criteria and 30 volunteers with defined criteria were selected from the subjects aged between 55 and 88 who applied to Gazi University Health Research.Statistical analysis of the data showed that there was a significant difference between the endgroups and biomarkers for the early diagnosis of Alzheimer's disease, but this complicated matter has to be investigated in more comprehensive and detailed studie. ResultsIn the present study, we investigated oxidative stress parameters, thiol-disulphide balance, ischemia modified abumin and seruloplasmin in parallel with the impairment in cognitive dysfunction from control group to Mild Cognitive Impairment (MCD) and AD group by using a newly-developed method. ConclusionsThis is the first study in literature comparing Early Stages Alzheimer Disease (ESAD), MCD and healthy volunteer groups. Our study has revealed that these newly developed tests may be candidates as oxidative stress biomarkers in pathgenesis of AD. However it was concluded that more comprehensive and detailed studies are required to enlighten this issue.

PLG72 levels increase in early phase of Alzheimer\u2019s disease but decrease in late phase

pLG72, named as D-amino acid oxidase activator (although it is not an activator of D-amino acid oxidase demonstrated by later studies), in mitochondria has been regarded as an important modulator of D-amino acid oxidase that can regulate the N-methyl-D-aspartate receptor (NMDAR). Both oxidative stress in mitochondria and NMDAR neurotransmission play essential roles in the process of neurodegenerative dementia. The aim of the study was to investigate whether pLG72 levels changed with the severity of neurodegenerative dementia. We enrolled 376 individuals as the overall cohort, consisting of five groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild Alzheimer’s disease [AD], moderate AD, and severe AD. pLG72 levels in plasma were measured using Western blotting. The severity of cognitive deficit was principally evaluated by Clinical Dementia Rating Scale. A gender- and age- matched cohort was selected to elucidate the effects of gender and age. pLG72 levels increased in the MCI and mild AD groups when compared to the healthy group. However, pLG72 levels in the moderate and severe AD groups were lower than those in the mild AD group. D-serine level and D- to total serine ratio were significantly different among the five groups. L-serine levels were correlated with the pLG72 levels. The results in the gender- and age- matched cohort were similar to those of the overall cohort. The finding supports the hypothesis of NMDAR hypofunction in early-phase dementia and NMDAR hyperfunction in late-phase dementia. Further studies are warranted to test whether pLG72 could reflect the function of NMDAR.

Features of a modified WHO/UCLA AVLT performance in amnestic mild cognitive impairment and mild Alzheimer's disease

Objective: To compare the features of a modified WHO/UCLA AVLT performance in the cognitive normal, amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (mild AD) patients. Method: A total of 105 cases of cognitivenormal (CN), 48 aMCI and 50 mild AD patients were included between 2016 and 2018. All subjects undertook detailed neuropsychological tests and brain MRI/CT scan. Results: The total score of five learning trials in CN, aMCI and AD groups were 53.9±6.9, 34.6±8.3 and 23.7±6.2, respectively (P<0.001). The score of 20-min delay recallwere 12.5±1.6, 4.3±3.0 and 0.6±1.0, respectively (P<0.001) in three groups. The score of cued recall were 13.0±1.4, 7.0±2.4 and 2.6±2.0, respectively (P<0.001). The score of 20-min delay recall had the largest effect sizes between CN and aMCI groups (Cohen'd=3.8, 95%CI,3.3-4.4), and CN and mild AD groups (Cohen'd=8.1, 95%CI 7.1-9.1). Cued recall had the largest effect size between aMCI and mild AD groups (Cohen'd=2.04, 95%CI 1.5-2.5). The scores of learning total score, 20-min delay recall, cued recall and recognition had the strong relationships with the scores of mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) , but obtaining moderate relationships with Boston naming test and trail making test (TMT) and weak relationships with digit span and figure copy. Age and education had no relationship with the main indices of this modified AVLT. Conclusions: The modified WHO/UCLA AVLT is still an age and education fair test to assess memory domain function. Qualitative analysis of AVLT profiles may be useful to differentiate the CN, aMCI and mild AD in Chinese sample.

Relationship between Alzheimer's disease and non-verbal listening comprehension obstacle

Objective To study the relationship between Alzheimer's disease(AD)and non-verbal listening comprehension obstacle, and to observe the different specific performance of AD patients in the non-verbal listening comprehension tests involving music and non-verbal semantics, in order to identify the value of these tests in the differential diagnosis of AD. Methods The internalized 104 subjects meeting inclusion and exclusion criteria were divided into 4 groups of normal group(n=24), a-MCI group(amnesia-mild cognitive impairment, n=30), mild-AD group(n=27)and moderate AD group(n=23). All subjects received a series of central non-verbal listening comprehension tests which were scored and evaluated, including categorizing and naming according to the sound which involved the non-verbal semantic aspect, judging the emotion and rhythm according to the melody which involved the music aspect.Then the scores were analyzed.Mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)were used for assessing the degrees of cognitive impairment. Results All test scores had a positive moderate to high correlations with MMSE and MoCA(all r>0.4, P<0.01), in which sound classification and nomination had better positive correlations than other tests.The statistically significant differences were found in all tests among the four groups(all P<0.05). There was a significant difference in sound nomination between a-MCI group and normal group(P< 0.05). There were significant differences in sound classification, nomination and judging melody rhythm between mild AD group and normal group or a-MCI group(both P<0.05). There were significant differences in all tests between moderate AD group and normal group or a-MCI group(both P<0.05). The sound classification tests, especially sound nomination tests, had better diagnostic value than the rhythm and emotion judgment tests for identifying AD. Conclusions Patients with AD, even with a-MCI, can develop the non-verbal listening comprehension obstacle, which is aggravated along with the exacerbation of cognitive impairment.AD patient's semantic aspect-involving non-verbal listening ability degeneration is faster than involving the music aspect.Non-verbal listening comprehension tests involving non-verbal semantic aspect, especially sound nomination tests, have better diagnostic values. Key words: Alzheimer's disease; Comprehension; Listening comprehension obstacle

Sentence Context and Word-Picture Cued-Recall Paired-Associate Learning Procedure Boosts Recall in Normal and Mild Alzheimer's Disease Patients.

Introduction The aim of this study was to employ the word-picture paradigm to examine the effectiveness of combined pictorial illustrations and sentences as strong contextual cues. The experiment details the performance of word recall in healthy older adults (HOA) and mild Alzheimer's disease (AD). The researchers enhanced the words' recall with word-picture condition and when the pair was associated with a sentence contextualizing the two items. Method The sample was composed of 18 HOA and 18 people with mild AD. Participants memorized 15 pairs of words under word-word and word-picture conditions, with and without a sentence context. In the paired-associate test, the first item of the pair was read aloud by participants and used to elicit retrieval of the associated item. Results The findings suggest that both HOA and mild-AD pictures improved item recall compared to word condition such as sentences which further enabled item recall. Additionally, the HOA group performs better than the mild-AD group in all conditions. Conclusions Word-picture and sentence context strengthen the encoding in the explicit memory task, both in HOA and mild AD. These results open a potential window to improve the memory for verbalized instructions and restore sequential abilities in everyday life, such as brushing one's teeth, fastening one's pants, or drying one's hands.

The Efficiency and Efficacy of On-Line Vs. Off-Line Cognitive Rehabilitation Therapies: Can a Wireless Interactive Cognitive Rehabilitation System on Dementia Patients Replace Rehabilitation Therapists?

There have been increasing attempts to control memory, attention and naming difficulties of the elderly by using game applications on a tablet device. It is necessary to take into account several factors for such attempts to be realized effectively. This study applied the group rehabilitation therapy programs of a wireless interactive cognitive rehabilitation system and of paper-pencil methods to patients with dementia and the elderly with mild cognitive impairment, respectively, and sought to present the factors to be considered in order to achieve both efficiency and efficacy of cognitive rehabilitation therapies. The mild cognitive impairment group had few difficulties in participating in games connected with multi-users, understanding training directions and adjusting a training level of difficulty and speed, whereas the mild AD group, whose cognition fell below -2SD in normative data, had difficulties while a group rehabilitation program was being carried out with only one therapist and a device, and were continually directed one to one on how to use the device. In the therapy program of a paper & pencil method, while the mild cognitive impairment group understood clearly every task, the dementia group could complete the task only under assistant’s repeated directions and explanation. The reason why engineering techniques have been applied in cognitive rehabilitation training programs for the elderly with dementia is the advantages of such programs like immediate feedback depending on user’s performance and a decreased burden of labor force. It is cognitive functions of the device user that serve as a highly significant variable to predict efficiency and effectiveness of such engineering techniques.

The clinical relationship between different degrees of Alzheimer′s disease and trace elements

Objectives To explore the clinical relationship between different degrees of Alzheimer′s disease(AD)and trace elements and to provide information for control and prevention of AD. Methods From January 2015 to December 2015, 125 AD patients in psychiatric hospital of the same city were randomly selected and divided into mild(n=28), moderate(n=42), and severe(n=55)AD group according to dementia degree.40 volunteers were recruited as healthy control group.The fasting contents of serum copper, iron and zinc were measured, and the data were statistically analyzed. Results Compared with healthy control group, the content of serum copper was(16.32±6.54)g/L in control group, (16.90±6.37)g/L in mild group, (20.31±6.74)g/L in moderate group, and(21.29±6.92)g/L in severe AD group, increasing gradually in mild, moderate, and severe AD groups versus control group(F=6.318, P<0.001). Serum copper levels howed significantly differences(P<0.05)in severe AD group versus healthy control group or the mild AD group.The content of serum iron was(9.17±4.71)g/L in control group, (7.82±4.67)g/L in mild AD group, (7.71±4.42)g/L in moderate AD group and(7.28±4.19)g/L in severe AD group, decreasing significantly in mild, moderate and severe AD groups versus healthy control group(F=3.331, P=0.021). The content of serum zinc was(100.67±9.78)g/L in control, (81.78±9.91)g/L in mild, (66.48±9.37)g/L in moderate, and(71.55±8.97)g/L in severe AD group, decreasing significantly in mild, moderate and severe AD group versus the control group(F=123.168, P<0.001). Serum copper, iron and zinc contents showed statistically differences in mild, moderate and severe AD groups versus in healthy control group(P<0.05). There was no interaction between dementia degree and serum iron concentration.In patients with moderate dementia and serum copper concentrations close to 20.31 mmol/L(F=10.098, P=0.000), or in patients with moderate dementia and serum zinc concentrations close to 66.48 mmol/L(F=7.433, P=0.001), behavioral and psychological symptoms were most obvious. Conclusions The serum levels of trace elements in patients with different degrees of AD may change differently.The content of serum copper is increased gradually, while the contents of serum iron and zinc are significantly decreased along with increased AD degree. Key words: Alzheimer disease; Micronutrients

Symptoms of androgen deficiency in Chinese older men with mild cognitive impairment

Geriatric Depression Scale (GDS). Cognitive function tests including mini mental status examination (MMSE), letter fluency, Boston naming test, verbal learning tests, and trail making test-A (TMT-A)were conducted. Blessed Dementia Scale-Activities of Daily Living (BDS-ADL) was utilized to assess daily functioning. In both groups, correlation between GDS with cognitive function measures and BDS-ADL were analyzed. Results: In aMCI group, correlation analysis showed a significant positive correlation between GDS and BDS-ADL (r1⁄40.321, p<0.001), but no significant correlations were observed between GDS and cognitive function measures. In contrast, correlation analysis in mild AD group showed no significant correlation between GDS and BDS-ADL, but a significant positive correlation was found between GDS with TMT-A time (r1⁄40.315, p<0.05). Conclusions: The present study suggests that depression severity has negative impact on daily functioning rather than cognitive functioning in patients with MCI. However, in patients with AD cognitive functioning rather than daily functioning is affected by depression severity.

Basal forebrain atrophy predicts clinical progression in the nondemented elderly

hippocampal and sub-hippocampal volumes were not statistically significant. In contrast, despite the small sample sizes, the mild AD group exhibited significantly greater WM microstructural integrity changes in the medial temporal lobe structures, compared to aMCI group at p < 0.05. These findings suggest that the white matter integrity changes in the medial temporal lobe may be a more robust early biomarker than cortical volume changes to distinguish mild AD from aMCI.

Automatic Voxel-Based Morphometry of Structural MRI by SPM8 plus Diffeomorphic Anatomic Registration Through Exponentiated Lie Algebra Improves the Diagnosis of Probable Alzheimer Disease

The necessity for structural MRI is greater than ever to both diagnose AD in its early stage and objectively evaluate its progression. We propose a new VBM-based software program for automatic detection of early specific atrophy in AD. A target VOI was determined by group comparison of 30 patients with very mild AD and 40 age-matched healthy controls by using SPM. Then this target VOI was incorporated into a newly developed automated software program independently running on a Windows PC for VBM by using SPM8 plus DARTEL. ROC analysis was performed for discrimination of 116 other patients with AD with very mild stage (n = 45), mild stage (n = 30) and moderate-to-advanced stages (n = 41) from 40 other age-matched healthy controls by using a z score map in the target VOI. Medial temporal structures involving the entire region of the entorhinal cortex, hippocampus, and amygdala showed significant atrophy in the patients with very mild AD and were determined as a target VOI. When we used the severity score of atrophy in this target VOI, 91.6%, 95.8%, and 98.2% accuracies were obtained in the very mild AD, mild AD, and moderate-to-severe AD groups, respectively. In the very mild AD group, a high specificity of 97.5% with a sensitivity of 86.4% was obtained, and age at onset of AD did not influence this accuracy. This software program with application of SPM8 plus DARTEL to VBM provides a high performance for AD diagnosis by using MRI.