The TE4D-Cog: a new test for detecting early dementia in English-speaking populations

BACKGROUND: The screening test usually used to detect dementia (Mini Mental State Examination, MMSE) is limited by a ceiling effect and high false positive rates, as are other similar instruments. There is therefore a need for a more sensitive and specific screening tool to aid early detection and diagnosis of dementia. OBJECTIVE: The hypothesis of the study was that the TE4D-Cog would be more sensitive and specific than the MMSE in detecting mild cognitive impairment in patients with AD. METHOD: The TE4D (Test for the Early Detection of Dementia from Depression) was adapted from its original German version for English-speaking populations. This new scale (the TE4D-Cog) was then administered together with the MMSE and the cognitive subscale of the Alzheimer's disease Assessment Scale (ADAS-Cog) to 178 people with a diagnosis of Alzheimer's disease and 25 cognitively intact comparators. The sensitivity and specificity in detecting dementia of the TE4D-Cog and the MMSE were compared in those with mild dementia and those without dementia. RESULTS: The TE4D-cog had high sensitivity with an acceptable specificity and low false positive rate. It also had good concurrent validity, high inter-rater reliability, good internal consistency and strong predictive validity. CONCLUSIONS: The TE4D-Cog is easy to administer, short and acceptable. Results are independent of age, gender and level of education. The TE4D-Cog may therefore be a useful alternative to the MMSE as a dementia screening instrument.     

Cross-national comparison and validation of the Alzheimer's Disease Assessment Scale: results from the European Harmonization Project for Instruments in Dementia (EURO-HARPID)

BACKGROUND: The Alzheimer's Disease Assessment Scale (ADAS) is often used in international multicenter trials. Use across countries presupposes correct translation and adaptation of the scale, and maintenance of its psychometric properties. OBJECTIVES: To compare the various translations of the ADAS used in Western Europe, to design internationally harmonized translations and to validate these. SETTING: International cooperative study in eight European countries. METHODS: An inventory was made of existing versions of the ADAS-Cog used in eight European countries, and adaptations were made. The concurrent validity of the harmonized versions of the ADAS was tested in 283 patients with probable or possible Alzheimer's disease. The Nurses Observation Scale for Geriatrics (NOSGER), CAMCOG-R and MMSE was used to assess concordance between cognitive and behavioral measures. RESULTS: Differences between the versions mainly involved object naming, items for verbal memory, such as the number of trials allowed, the imagery value of the words selected as targets or distractors, and the number of parallel versions. These differences were eliminated by adapting and harmonizing the various versions of the ADAS-Cog. Thereafter, only small differences between the different countries were found, and patterns of correlation between ADAS-Cog, and the NOSGER, CAMCOG-R and MMSE were consistent. CONCLUSIONS: The study underlines the need to use harmonized versions of instruments for rating dementia in multinational studies. The findings indicate that the harmonization of the ADAS-Cog was successful.     

Depression in dementia: a comparative and validation study of four brief scales in the elderly Chinese

AIM: The study aimed to determine: (i) the diagnostic accuracy of four brief depression scales, the Geriatric Depression Scale (GDS), Even Briefer Assessment Scale for Depression (EBAS DEP), Single Question and Cornell Scale for Depression in Dementia (Cornell) in an elderly Chinese population with varying dementia severity; and (ii) which scale had the best diagnostic performance. METHOD: All four scales were administered to 88 elderly outpatients with dementia: 66 without and 22 with depression. Receiver Operating Characteristic (ROC) analysis was used to establish the optimal cut-off scores of the GDS, EBAS DEP and Cornell scales. The patients' dementia-severity was dichotomously categorized into mild and moderate-severe dementia, and the above analysis was repeated in both these groups to look at changes in the scales' diagnostic performance as dementia advances. RESULTS: The best diagnostic scale for detecting depression in dementia was the Cornell scale. Its optimal cut-off score was 6/7 (sensitivity 91.7%, specificity 80.0%) in the mild dementia group and 12/13 (sensitivity 70.0%, specificity 87.0%) in the more advanced dementia group. The optimal cut-off scores of the GDS and EBAS DEP also shifted to higher values when moving from the mild to the more advanced dementia groups, indicating the increasing difficulty on all these scales to detect depression with worsening cognitive impairment. The Single Question, however, was more robust with much less changes in its diagnostic parameters in both dementia cohorts: sensitivity 58.3%, specificity 90.0% for mild dementia, and 60.0 and 84.8%, respectively, for more advanced dementia. CONCLUSION: An efficient strategy to diagnose depression in dementia amongst elderly Chinese patients is to administer the Single Question followed by, when necessary, the Cornell scale.     

The EEG in progressive dialysis encephalopathy: the EEG in diagnosing and screening for PDE. (Part. I)

An EEG study was carried out on 50 patients undergoing chronic dialysis, 5 of whom had progressive dialysis encephalopathy (PDE), with the aim of confirming the reliability of EEG for diagnosing PDE and detecting patients at risk reported in previous papers. The outcome of the study confirms the high sensitivity of EEG for these purposes.

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Sommario È stato effettuato uno studio EEG su una popolazione di 50 pazienti in trattamento dialitico cronico. Cinque di essi erano affetti da Encefalopatia Dialitica Progressiva. Lo studio è stato effettuato per confermare la attendibilità diagnostica di questo esame in questa encefalopatia e nello screening di pazienti a rischio, come già riportato in alcune osservazioni precedenti. I risultati ottenuti confermano l'elevata sensibilità di questo esame come mezzo di diagnosi e screening della Encefalopatia Dialitica Progressiva.

     

Relationship of phosphodiesterase 4D (PDE4D) gene polymorphisms with risk of ischemic stroke: a hospital based case-control study

Background: Stroke remains a leading cause of death and disability worldwide. Ischemic stroke (IS) accounts for around 80–85% of total stroke and is a complex polygenic multi-factorial disorder which is affected by a complex combination of vascular, environmental, and genetic factors.

Objective: The study was conducted with an aim to examine the relationship of single nucleotide polymorphisms (SNPs) of PDE4D (T83C, C87T, and C45T) gene with increasing risk of IS in patients in North Indian population.

Methods: In this hospital-based case-control study, 250 IS subjects and 250 age-and sex-matched control subjects were enrolled from the Neurosciences Centre, A.I.I.M.S., New Delhi, India. Deoxyribonucleic acids (DNAs) were extracted using the conventional Phenol–Chloroform isolation method. Different genotypes were determined by Polymerase chain reaction– Restriction fragment length polymorphism method. Odds ratio (OR) and 95% Confidence Interval (CI) of relationship of polymorphisms with risk of IS were calculated by conditional multivariable regression analysis.

Results: High blood pressure, low socioeconomic status, dyslipidemia, diabetes, and family history of stroke were observed to be statistically significant risk factors for IS. Multivariable adjusted analysis demonstrated a statistically significant relationship between SNP 83 of PDE4D gene polymorphism and increasing odds of IS under the dominant model of inheritance (OR, 1.59; 95% CI, 1.02 to 2.50; p value = 0.04) after adjustment of potential confounding variables. Stratified analysis on the basis of TOAST classification demonstrated a statistically significant association for increasing 2.73 times odds for developing large vessel disease stroke as compared to controls (OR, 2.73; 95% CI, 1.16 to 0.02; p value = 0.02). We did not find any significant association of SNPs (C87T and C45T) of the PDE4D gene with the risk of IS.

Conclusion: SNP 83 of PDE4D gene may increase the risk for developing IS whereas SNP 87 and SNP45 of PDE4D may not be associated with the risk of IS in the North Indian population. Prospective cohort studies are required to corroborate these findings.     

Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta-analyses

The relationships of digit ratio (2D:4D) with the length of AR (CAG)n, and testosterone levels from saliva and blood have been extensively debated over the years. This research including three studies further clarifies such controversies. To do so, we re-examined the relationships between the length of AR (CAG)n, 2D:4D, and current testosterone levels, through replication study and meta-analysis for each study. The results indicate: (a) the length of AR (CAG)n is not significantly associated with 2D:4D; (b) current testosterone levels are not significantly associated with the ratio; and (c) the length is not significantly associated with testosterone levels. Thus, AR (CAG)n and current testosterone levels are not significantly related to 2D:4D at individual level.     

Screening for elder abuse in dementia in the LASER-AD study: prevalence, correlates and validation of instruments

BACKGROUND: Several studies have investigated abusive behaviour by carers towards people with dementia, most using unvalidated scales; only two reported correlates of abuse after controlling for mediators and confounders, and these controlled for different factors. OBJECTIVE: To investigate the acceptability and validity of the Modified Conflict Tactics Scale (MCTS) and abuse correlates. METHODS: Eighty-six people with Alzheimer's disease and their family carers, originally recruited for a representative community study were interviewed. We asked carers about acceptability of the MCTS and investigated its validity by comparing scores to the Minimum Data Set (MDS) abuse screen (an objective measure) and testing hypotheses that MCTS score would correlate with the COPE dysfunctional coping scale but not carer education. RESULTS: Twenty-four (27.9%) were identified as abuse cases by interview. No care recipients (CRs) screened positive for abuse using the MDS screen. Seventy-two (83.7%) participants thought that the scale was acceptable, ten (11.6%) that it was neither acceptable nor unacceptable, and three (3.5%) that it was unacceptable. As hypothesised, MCTS scores correlated with dysfunctional coping scale score but not carer education. CONCLUSIONS: This is the most comprehensive study so far in this field. The MCTS was acceptable and had convergent and discriminant validity for measuring carer abuse. The MDS failed to identify cases of abuse. Carer male gender and burden, and greater CR irritability, cognitive impairment but less functional impairment predicted carer abusive behaviour. Our findings appear to refute UK government elder abuse reduction policy which assumes that few incidents of abuse arise from carer stress.     

The automated preprocessing pipe-line for the estimation of scale-wise entropy from EEG data (APPLESEED): Development and validation for use in pediatric populations

It is increasingly understood that moment-to-moment brain signal variability – traditionally modeled out of analyses as mere “noise” – serves a valuable functional role related to development, cognitive processing, and psychopathology. Multiscale entropy (MSE) – a measure of signal irregularity across temporal scales – is an increasingly popular analytic technique in human neuroscience calculated from time series such as electroencephalography (EEG) signals. MSE provides insight into the time-structure and (non)linearity of fluctuations in neural activity and network dynamics, capturing the brain’s moment-to-moment complexity as it operates on multiple time scales. MSE is emerging as a powerful predictor of developmental processes and outcomes. However, differences in data preprocessing and MSE computation make it challenging to compare results across studies. Here, we (1) provide an introduction to MSE for developmental researchers, (2) demonstrate the effect of preprocessing procedures on scale-wise entropy estimates, and (3) establish a standardized EEG preprocessing and entropy estimation pipeline that adapts a critical modification to the original MSE algorithm, and generates reliable scale-wise entropy estimates capable of differentiating developmental stages and cognitive states. This novel pipeline – the Automated Preprocessing Pipe-Line for the Estimation of Scale-wise Entropy from EEG Data (APPLESEED) is fully automated, customizable, and freely available for download from https://github.com/mhpuglia/APPLESEED.     

The development and validation of the Dementia Quality of Life Scale for Older Family Carers (DQoL-OC)

Purpose: Little is known about how caregiving affects the quality of life (QoL) of older family carers and no dementia and age-specific QoL scale is available for use with this population. This study aimed to develop and validate a unique dementia caregiving- and age-specific tool – the ‘Dementia Quality of Life Scale for Older Family Carers’ (DQoL-OC).

Methods: The scale items were identified in focus groups with older family carers in the UK. Content and face validity were evaluated by a panel of six experts. A set of 100 items assessed on a 5-point Likert scale was tested with 182 older family carers. Test–re-test reliability was conducted with 18 individuals. Exploratory factor analysis was used to identify the QoL model and reduce the number of scale items. Convergent construct validity and internal consistency were also established.

Results: A one-factor solution containing 22 items was obtained. Test–re-test reliability (lower bound r = 0.835; p < 0.001), internal consistency (Cronbach's α = 0.936), and convergent construct validity were established. Significantly lower levels of QoL were found in female older carers; those who perceived their relatives with dementia as being at the earlier stages of the disease and with unstable dementia symptoms; those providing care more hours per day and more days per week; and those in younger-old age.

Conclusions: The DQoL-OC is a valid and reliable scale that will be useful for research and in clinical practice with older family carers of people with dementia. These study results will inform future health and social care aiming to improve life quality for this overlooked population of carers.     

2nd to 4th digit ratio (2D:4D) and number of sex partners: evidence for effects of prenatal testosterone in men

The number of sexual partners per individual (NSP) is an important component of sexual behaviour. Here, we report two studies concerning the relationship between a probable negative correlate of prenatal testosterone, the ratio of the length of 2nd and 4th digits (2D:4D), and NSP in men. The right hand 2D:4D ratio appears to be more strongly related to prenatal testosterone than does the left hand. Accordingly we found: (a) in a sample of 99 German heterosexual male undergraduates right hand 2D:4D (but not left hand 2D:4D) was significantly negatively associated with reported lifetime NSP. The relationship between NSP and 2D:4D was independent of free testosterone, but free testosterone also showed a weak positive association with NSP (b) in a sample of 79 heterosexual and 95 homosexual Austrian men we found a significant negative association between right hand 2D:4D (but not left hand 2D:4D) and reported NSP in past year for heterosexual but not for homosexual men. The association in heterosexuals was independent of age, years of education, occupation and relationship status. We conclude that male NSP is likely to be influenced by the long-term organisational effects of prenatal testosterone. The relationship between NSP and 2D:4D appears to be confined to heterosexual men.     

Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age

Summary. Background: In recent years, a growing number of studies has focused on the dopamine D4 receptor gene (DRD4) as mediating the susceptibility to attention-deficit/hyperactivity disorder (ADHD). While their results are contradictory, the reason for this inconsistency remains as yet unclear. Method: The present study sought to examine the association between ADHD and the DRD4 exon III polymorphism during child development using longitudinal data from a high-risk community sample (n=265, 129 females, 126 males) who have been followed from birth to 11 years of age. Results: Higher rates of ADHD were observed in boys with the 7 repeat allele of exon III than in boys with other alleles at the ages of 4 1/2 (Fishers exact test, p=.061), 8 (p=.026), and 11 years (p=.005). Boys with this allele also exhibited higher rates of persistent disorder (p=.024). In girls, a trend towards an association (p=.055) with the 7 repeat allele emerged only at preschool age. Conclusions: These findings provide additional evidence for the role of the dopamine D4 receptor in ADHD during the course of child development.     

Evaluation of single nucleotide polymorphisms in the phosphodiesterase 4D gene (PDE4D) and their association with ischaemic stroke in a large German cohort

Genetic fine mapping of the first locus identified for genetically complex forms of stroke, STRK1 (which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (PDE4D) gene as a good candidate gene. Association analysis of single nucleotide polymorphisms (SNPs) in the PDE4D gene in an Icelandic stroke cohort demonstrated genetic association between six SNPs in the 5' region of PDE4D and ischaemic stroke. The present study aimed to test whether the same six SNPs in PDE4D were also associated with stroke in a large stroke cohort from northern Germany (stroke patients with acute completed ischaemic stroke: n = 1181; population based controls: n = 1569). None of the six SNPs showed significant association with ischaemic stroke in the whole stroke sample before and after adjustment for conventional stroke risk factors (age, sex, hypertension, diabetes, and hypercholesterolaemia). Haplotype analysis did also not reveal any significant association. Marginally positive statistical measures of association in the subgroup with cardioembolic stroke did not remain significant after correction for multiple testing. In conclusion, this study was unable to demonstrate an association between the six SNPs which had showed significant single marker association with stroke in the Icelandic stroke cohort and ischaemic stroke in a large German cohort.     

Second to fourth digit length ratio (2D:4D) and adult sex hormone levels: new data and a meta-analytic review

The relative length of the second (index) to the fourth (ring) finger (2D:4D) is a putative negative correlate of prenatal testosterone (T) exposure. Therefore, 2D:4D (and to a lesser extent D(r-l), the difference between 2D:4D in the right hand and in the left hand) has often been used to study effects of prenatal androgenization on human behavior and cognition. However, evidence suggests that 2D:4D may also be related to levels of circulating sex hormones in adults. This would question the validity of 2D:4D as a means of studying the effects of prenatal sex hormones. Here we present new data from two non-clinical samples (64 women and 102 men) regarding the relationships of 2D:4D and D(r-l) with circulating sex hormone levels. We then present a meta-analytic review of all the present evidence regarding this issue. The results suggest that, in the normal population, 2D:4D and D(r-l) are not associated with adult sex hormone levels. The findings from this current study add to the growing body of evidence demonstrating that 2D:4D is a suitable tool to study the effects of prenatal androgenization on human behavior and cognition.