Predicting conversion to dementia in a memory clinic: A standard clinical approach compared with an empirically defined clustering method (latent profile analysis) for mild cognitive impairment subtyping

Introduction
Mild cognitive impairment (MCI) has clinical value in its ability to predict later dementia. A better understanding of cognitive profiles can further help delineate who is most at risk of conversion to dementia. We aimed to (1) examine to what extent the usual MCI subtyping using core criteria corresponds to empirically defined clusters of patients (latent profile analysis [LPA] of continuous neuropsychological data) and (2) compare the two methods of subtyping memory clinic participants in their prediction of conversion to dementia.

Methods
Memory clinic participants (MCI, n = 139) and age-matched controls (n = 98) were recruited. Participants had a full cognitive assessment, and results were grouped (1) according to traditional MCI subtypes and (2) using LPA. MCI participants were followed over approximately 2 years after their initial assessment to monitor for conversion to dementia.

Results
Groups were well matched for age and education. Controls performed significantly better than MCI participants on all cognitive measures. With the traditional analysis, most MCI participants were in the amnestic multidomain subgroup (46.8%) and this group was most at risk of conversion to dementia (63%). From the LPA, a three-profile solution fit the data best. Profile 3 was the largest group (40.3%), the most cognitively impaired, and most at risk of conversion to dementia (68% of the group).

Discussion
LPA provides a useful adjunct in delineating MCI participants most at risk of conversion to dementia and adds confidence to standard categories of clinical inference.

Age-related prevalence and met need for correctable and uncorrectable near vision impairment in a multi-country study

Purpose: To estimate the prevalence, potential determinants, and proportion of met need for near vision impairment (NVI) correctable with refraction approximately 2 years after initial examination of a multi-country cohort. Design: Population-based, prospective cohort study. Participants: People aged ≥35 years examined at baseline in semi-rural (Shunyi) and urban (Guangzhou) sites in China; rural sites in Nepal (Kaski), India (Madurai), and Niger (Dosso); a semi-urban site (Durban) in South Africa; and an urban site (Los Angeles) in the United States. Methods: Near visual acuity (NVA) with and without current near correction was measured at 40 cm using a logarithm of the minimum angle of resolution near vision tumbling E chart. Participants with uncorrected binocular NVA ≤20/40 were tested with plus sphere lenses to obtain best-corrected binocular NVA. Main Outcome Measures: Prevalence of total NVI (defined as uncorrected NVA ≤20/40) and NVI correctable and uncorrectable to >20/40, and current spectacle wearing among those with bilateral NVA ≤20/63 improving to >20/40 with near correction (met need). Results: Among 13 671 baseline participants, 10 533 (77.2%) attended the follow-up examination. The prevalence of correctable NVI increased with age from 35 to 50-60 years and then decreased at all sites. Multiple logistic regression modeling suggested that correctable NVI was not associated with gender at any site, whereas more educated persons aged >54 years were associated with a higher prevalence of correctable NVI in Nepal and India. Although near vision spectacles were provided free at baseline, wear among those who could benefit was <40% at all but 2 centers (Guangzhou and Los Angeles). Conclusions: Prevalence of correctable NVI is greatest among persons of working age, and rates of correction are low in many settings, suggesting that strategies targeting the workplace may be needed.

Causes and five-year incidence of blindness and visual impairment in urban southern China:The Liwan Eye Study

PURPOSE. We determined the causes and five-year incidence of blindness and visual impairment (VI) in an adult, urban Chinese population. METHODS. Participants underwent a comprehensive eye examination at baseline in 2003 and then five years later. The World Health Organization (WHO) and United States (US) definitions were used to define incident blindness (WHO visual acuity [VA] < 20/400 in the better-seeing eye, US VA ≤ 20/200) and incident VI (WHO VA < 20/60-20/400, US VA < 20/40->20/200). RESULTS. Among 1405 baseline participants, 924 (75%) of 1232 survivors (87.7%) participated in the 5-year follow-up. The incidences of VI and blindness were 5.38% (95% confidence interval [CI] 3.99% ~ 7.07%) and 0.33% (95% CI 0.07% ~ 0.95%), respectively, based on the WHO definition, and 9.85% (95% CI 7.96% ~ 12.0%) and 1.42% (95% CI 0.76% ~ 2.41%), respectively, based on the US definition. Incidence of blindness and VI (WHO definition) increased significantly with older age (P < 0.001) and poorer baseline presenting VA in the worse-seeing eye (P < 0.001). The leading cause of best-corrected VI (WHO definition) was cataract (64.6%), whereas the main causes of presenting VI were refractive error (40.4%) and cataract (38.4%). CONCLUSIONS. The incidence of VI in urban Southern China is high. The major causes are unoperated cataract and undercorrected refractive error, reflecting the need for better surgical and refractive care, even in this urban setting. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Causes and prevalence of visual impairment among adults in the United States.

OBJECTIVES: To estimate the cause-specific prevalence and distribution of blindness and low vision in the United States by age, race/ethnicity, and gender, and to estimate the change in these prevalence figures over the next 20 years. METHODS: Summary prevalence estimates of blindness (both according to the US definition of < or =6/60 [< or =20/200] best-corrected visual acuity in the better-seeing eye and the World Health Organization standard of < 6/120 [< 20/400]) and low vision (< 6/12 [< 20/40] best-corrected vision in the better-seeing eye) were prepared separately for black, Hispanic, and white persons in 5-year age intervals starting at 40 years. The estimated prevalences were based on recent population-based studies in the United States, Australia, and Europe. These estimates were applied to 2000 US Census data, and to projected US population figures for 2020, to estimate the number of Americans with visual impairment. Cause-specific prevalences of blindness and low vision were also estimated for the different racial/ethnic groups. RESULTS: Based on demographics from the 2000 US Census, an estimated 937 000 (0.78%) Americans older than 40 years were blind (US definition). An additional 2.4 million Americans (1.98%) had low vision. The leading cause of blindness among white persons was age-related macular degeneration (54.4% of the cases), while among black persons, cataract and glaucoma accounted for more than 60% of blindness. Cataract was the leading cause of low vision, responsible for approximately 50% of bilateral vision worse than 6/12 (20/40) among white, black, and Hispanic persons. The number of blind persons in the US is projected to increase by 70% to 1.6 million by 2020, with a similar rise projected for low vision. CONCLUSIONS: Blindness or low vision affects approximately 1 in 28 Americans older than 40 years. The specific causes of visual impairment, and especially blindness, vary greatly by race/ethnicity. The prevalence of visual disabilities will increase markedly during the next 20 years, owing largely to the aging of the US population.

A population-based study of visual impairment among pre-school children in Beijing: the Beijing study of visual impairment in children.

PURPOSE: To evaluate the prevalence and causes of visual impairment among Chinese children aged 3 to 6 years in Beijing. DESIGN: Population-based prevalence survey. METHODS: Presenting and pinhole visual acuity were tested using picture optotypes or, in children with pinhole vision < 6/18, a Snellen tumbling E chart. Comprehensive eye examinations and cycloplegic refraction were carried out for children with pinhole vision < 6/18 in the better-seeing eye. RESULTS: All examinations were completed on 17,699 children aged 3 to 6 years (95.3% of sample). Subjects with bilateral correctable low vision (presenting vision < 6/18 correctable to >or= 6/18) numbered 57 (0.322%; 95% confidence interval [CI], 0.237% to 0.403%), while 14 (0.079%; 95% CI, 0.038% to 0.120%) had bilateral uncorrectable low vision (best-corrected vision of < 6/18 and >or= 3/60), and 5 subjects (0.028%; 95% CI, 0.004% to 0.054%) were bilaterally blind (best-corrected acuity < 3/60). The etiology of 76 cases of visual impairment included: refractive error in 57 children (75%), hereditary factors (microphthalmos, congenital cataract, congenital motor nystagmus, albinism, and optic nerve disease) in 13 children (17.1 %), amblyopia in 3 children (3.95%), and cortical blindness in 1 child (1.3%). The cause of visual impairment could not be established in 2 (2.63%) children. The prevalence of visual impairment did not differ by gender, but correctable low vision was significantly (P < .0001) more common among urban as compared with rural children. CONCLUSION: The leading causes of visual impairment among Chinese preschool-aged children are refractive error and hereditary eye diseases. A higher prevalence of refractive error is already present among urban as compared with rural children in this preschool population.

Presbyopia and near-vision impairment in rural northern China.

PURPOSE: Presbyopia limits activities of daily living, but population-based data from rural China are scarce. METHODS: A population-based, cross-sectional study was conducted in 2009 among all persons aged 40+ years in a rural area near Shenyang, China. Distance and near VA were measured using logMAR E charts. Individuals with pinhole-corrected distance vision ≥20/63 underwent detailed eye examination and near refraction. RESULTS: A total of 1008 (91.5%) respondents were examined (mean age, 58.4 ± 10.7 years for men, 56.8 ± 9.89 years for women). Women and older subjects were more likely to participate. The prevalence of functional presbyopia (near vision <20/50 [N8] improved by ≥1 line with correction) was 67.3% (95% confidence interval [CI], 64.30%-70.09%), increasing from 27.6% at 40 to 49 years of age to 81.8% at 60 to 69 years. Multivariate analysis showed that older age (P < 0.001), but not gender or education, was significantly associated with a higher risk of presbyopia. Self-reported presbyopic spectacle correction coverage was 51.5%. In multivariate logistic regression models, worse presenting near vision (P = 0.013) and higher required spherical equivalent power (P < 0.001) were associated with having correction, while age, gender, education, and distance vision were unassociated. Major barriers reported by persons without near correction included poor quality of available glasses (33.1%) and lack of awareness of the condition and its treatment (28.8%). CONCLUSIONS: Presbyopia is highly prevalent in rural China, and nearly half of affected persons have no access to correction. Interventions should focus on education and improvement in the quality of refractive services.

Quality of life and near vision impairment due to functional presbyopia among rural Chinese adults.

PURPOSE: To evaluate the impact of near-vision impairment on visual functioning and quality of life in a rural adult population in Shenyang, northern China. METHODS: A population-based, cross-sectional study was conducted among persons aged 40+ years, during which functional presbyopia (correctable presenting near vision < 20/50 [N8] at 40 cm) was assessed. Near-vision-related quality of life and spectacle usage questionnaires were administered by trained interviewers to determine the degree of self-rated difficulty with near tasks. RESULTS: A total of 1008 respondents (91.5% of 1102 eligible persons) were examined, and 776 (78%) of completed the questionnaires (mean age, 57.0 ± 10.2 years; 63.3% women). Near-vision spectacle wearers obtained their spectacles primarily from markets (74.5%) and optical shops (21.7%), and only 1.14% from eye clinics. Among 538 (69.3%) persons with functional presbyopia, self-rated overall (distance and near) vision was worse (P < 0.001) and difficulty with activities of daily living greater (P < 0.001) than among nonpresbyopes. Odds of reporting any difficulty with daily tasks remained higher (OR = 2.32; P < 0.001) for presbyopes after adjustment for age, sex, education and distance vision. Compared to persons without presbyopia, presbyopic persons were more likely to report diminished accomplishment due to vision (P = 0.01, adjusted for age, sex, education, and distance vision.) CONCLUSIONS: Difficulties with activities of daily living and resulting social impediments are common due to presbyopia in this setting. Most spectacle wearers with presbyopia in rural China obtain near correction from sources that do not provide comprehensive vision care.

Fetal umbilical artery Doppler pulsatility index and childhood neurocognitive outcome at 12 years

OBJECTIVE: To determine whether an elevated fetal umbilical artery Doppler (UAD) pulsatility index (PI) at 28 weeks' gestation, in the absence of fetal growth restriction (FGR) and prematurity, is associated with adverse neurocognitive outcome in children aged 12 years.

METHODS: Prospective cohort study, comparing children with a normal fetal UAD PI (<90th centile) (n=110) and those with an elevated PI (≥90th centile) (n=40). UAD was performed at 28, 32 and 34 weeks gestation. At 12 years of age, all children were assessed under standardised conditions at Queen's University, Belfast, UK to determine cognitive and behavioural outcomes using the British Ability Score-II and Achenbach Child Behavioural Checklist Parent Rated Version under standardised conditions. Regression analysis was performed, controlling for confounders such as gender, socioeconomic status and age at assessment.

RESULTS: The mean age of follow-up was 12.4 years (±0.5 SD) with 44% of children male (n=63). When UAD was assessed at 28 weeks, the elevated fetal UAD group had lower scores in cognitive assessments of information processing and memory. Parameters included (1) recall of objects immediate verbal (p=0.002), (2) delayed verbal (p=0.008) and (3) recall of objects immediate spatial (p=0.0016). There were no significant differences between the Doppler groups at 32 or 34 weeks' gestation.

CONCLUSIONS: An elevated UAD PI at 28 weeks' gestation in the absence of FGR or prematurity is associated with lower scores of declarative memory in children aged 12 years. A potential explanation for this is an element of placental insufficiency in the presence of the appropriately grown fetus, which affects the development of the fetal hippocampus and information processing and memory long-term. These findings, however, had no impact on overall academic ability, mental processing and reasoning or overall behavioural function.

A Systematic Review of End-of-Life Visual Impairment in Open-Angle Glaucoma: An Epidemiological Autopsy

PURPOSE: Glaucoma patients are still at risk of becoming blind. It is of clinical significance to determine the risk of blindness and its causes to prevent its occurrence. This systematic review estimates the number of treated glaucoma patients with end-of-life visual impairment (VI) and blindness and the factors that are associated with this.

METHODS: A systematic literature search in relevant databases was conducted in August 2014 on end-of-life VI. A total of 2574 articles were identified, of which 5 on end-of-life VI. Several data items were extracted from the reports and presented in tables.

RESULTS: All studies had a retrospective design. A considerable number of glaucoma patients were found to be blind at the end of their life; with up to 24% unilateral and 10% bilateral blindness. The following factors were associated with blindness: (1) baseline severity of visual field loss: advanced stage of glaucoma or substantial visual field loss at the initial visit; (2) factors influencing progression: fluctuation of intraocular pressure (IOP) during treatment, presence of pseudoexfoliation, poor patient compliance, higher IOP; (3) longer time period: longer duration of disease and older age at death because of a longer life expectancy; and (4) coexistence of other ocular pathology.

CONCLUSIONS: Further prevention of blindness in glaucoma patients is needed. To reach this goal, it is important to address the risk factors for blindness identified in this review, especially those that can be modified, such as advanced disease at diagnosis, high and fluctuating IOP, and poor compliance.

Face matching impairment in developmental prosopagnosia

Developmental prosopagnosia (DP) is commonly referred to as ‘face blindness’, a term that implies a perceptual basis to the condition. However, DP presents as a deficit in face recognition and is diagnosed using memory-based tasks. Here, we test face identification ability in six people with DP, who are severely impaired on face memory tasks, using tasks that do not rely on memory. First, we compared DP to control participants on a standardised test of unfamiliar face matching using facial images taken on the same day and under standardised studio conditions (Glasgow Face Matching Test; GFMT). DP participants did not differ from normative accuracy scores on the GFMT. Second, we tested face matching performance on a test created using images that were sourced from the Internet and so vary substantially due to changes in viewing conditions and in a person’s appearance (Local Heroes Test; LHT). DP participants show significantly poorer matching accuracy on the LHT relative to control participants, for both unfamiliar and familiar face matching. Interestingly, this deficit is specific to ‘match’ trials, suggesting that people with DP may have particular difficulty in matching images of the same person that contain natural day-to-day variations in appearance. We discuss these results in the broader context of individual differences in face matching ability.

Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2

BACKGROUND: We report on a young female, who presents with a severe speech and language disorder and a balanced de novo complex chromosomal rearrangement, likely to have resulted from a chromosome 7 pericentromeric inversion, followed by a chromosome 7 and 11 translocation. RESULTS: Using molecular cytogenetics, we mapped the four breakpoints to 7p21.1-15.3 (chromosome position: 20,954,043-21,001,537, hg19), 7q31 (chromosome position: 114,528,369-114,556,605, hg19), 7q21.3 (chromosome position: 93,884,065-93,933,453, hg19) and 11p12 (chromosome position: 38,601,145-38,621,572, hg19). These regions contain only non-coding transcripts (ENSG00000232790 on 7p21.1 and TCONS_00013886, TCONS_00013887, TCONS_00014353, TCONS_00013888 on 7q21) indicating that no coding sequences are directly disrupted. The breakpoint on 7q31 mapped 200 kb downstream of FOXP2, a well-known language gene. No splice site or non-synonymous coding variants were found in the FOXP2 coding sequence. We were unable to detect any changes in the expression level of FOXP2 in fibroblast cells derived from the proband, although this may be the result of the low expression level of FOXP2 in these cells. CONCLUSIONS: We conclude that the phenotype observed in this patient either arises from a subtle change in FOXP2 regulation due to the disruption of a downstream element controlling its expression, or from the direct disruption of non-coding RNAs.

Mental imagery in interpreting – a neurocognitive perspective

The paper discusses mental imagery as an important part of information processing performed during interpreting. Mental imagery is examined to see if visual processing used to remember the source text or to facilitate its understanding helps to ‗off-load‘ other cognitive (mainly linguistic) resources in interpreting. The discussion is based on a neurocognitively-oriented depictivist model by Kosslyn (1994). The overview of mental imagery processes and systems is followed by the discussion of imagery used in interpreting. First, imagery development in student interpreters is described on the basis of a note-taking course for would-be consecutive interpreters organized by the author at AMU. The initial part of the course devoted to imagery involves visualizations of geographical, descriptive and narrative texts. The description abounds in authentic examples and presents conclusions for interpreting trainers. Later, imagery as employed by professional interpreters is discussed on the basis of a qualitative survey. General implications of the use of mental imagery for cognitive processing limitations in interpreting are presented in the concluding section.