The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK.

The C9orf72 hexanucleotide repeat expansion (HRE) is a common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The inheritance is autosomal dominant, but a high proportion of subjects with the mutation are simplex cases. One possible explanation is de novo expansions of unstable intermediate-length alleles (IAs). Using haplotype sharing trees (HSTs) with the haplotype analysis tool kit (HAPTK), we derived majority-based ancestral haplotypes of HRE samples and discovered that IAs containing ≥18-20 repeats share large haplotypes in common with the HRE. Using HSTs of HRE and IA samples, we demonstrate that the longer IA haplotypes are largely indistinguishable from HRE haplotypes and that several ≥18-20 IA haplotypes share over 5 Mb (>600 markers) haplotypes in common with the HRE haplotypes. These analysis tools allow physical understanding of the haplotype blocks shared with the majority-based ancestral haplotype. Our results demonstrate that the haplotypes with longer IAs belong to the same pool of haplotypes as the HRE and suggest that longer IAs represent potential premutation alleles.

Education-Based Cutoffs for Cognitive Screening of Alzheimer's Disease.

INTRODUCTION: The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer's disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. METHODS: CERAD-nb scores were obtained from AD patients (n = 389, 58% women, mean age 74.0 years) and from controls (n = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden's J was calculated for the overall performance and accuracy of each of the measures. RESULTS: Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. CONCLUSIONS: Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.

Computer-based Eye-tracking Analysis of King-Devick Test Differentiates Persons With Idiopathic Normal Pressure Hydrocephalus From Cognitively Unimpaired.

BACKGROUND: Functional defects in eye movements and reduced reading speed in neurodegenerative diseases represent a potential new biomarker to support clinical diagnosis. We investigated whether computer-based eye-tracking (ET) analysis of the King-Devick (KD) test differentiates persons with idiopathic normal pressure hydrocephalus (iNPH) from cognitively unimpaired [control (CO)] and persons with Alzheimer's disease (AD). METHODS: We recruited 68 participants (37 CO, 10 iNPH, and 21 AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating interview. The KD reading test was performed using computer-based ET. We analyzed the total time used for the reading test, number of errors, durations of fixation and saccade, and saccade amplitudes. RESULTS: The iNPH group significantly differed from the CO group in the KD test mean total time (CO 69.3 s, iNPH 87.3 s; P ≤0.009) and eye-tracking recording of the mean saccade amplitude (CO 3.6 degree, iNPH 3.2 degree; P ≤0.001). The AD group significantly differed from the CO group in each tested parameter. No significant differences were detected between the iNPH and AD groups. CONCLUSION: For the first time, we demonstrated altered reading ability and saccade amplitudes in patients with iNPH.

Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study.

BACKGROUND: Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU). METHODS: This prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients-ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)-with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change in cognitive functioning observed by a close informant, as well as the presence of self-reported depressive and post-traumatic symptoms. RESULTS: The groups differed (effect size η2p = 0.065, p = 0.004) in the total cognitive score, calculated from neuropsychological measures in three domains (attention, executive functions, and memory). Both ICU-treated (p = 0.011) and ward-treated patients (p = 0.005) performed worse than home-isolated patients. Among those with more than 12 years of education, ICU-treated patients performed worse in the attention domain than ward-treated patients (p = 0.021) or non-COVID controls (p = 0.045); ICU-treated male patients, in particular, were impaired in executive functions (p = 0.037). CONCLUSIONS: ICU-treated COVID-19 patients, compared to patients with less severe acute COVID-19 or non-COVID controls, showed more severe long-term cognitive impairment. Among those with more than 12 years of education, impairment existed particularly in the domains of attention and for men, of executive functions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04864938, retrospectively registered February 9, 2021.

Mortality in individuals with childhood ADHD or subthreshold symptoms - a prospective perinatal risk cohort study over 40 years.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with negative life outcomes and recent studies have linked it to increased mortality. These studies have examined nationwide registers or clinic-referred samples and mostly included participants up until the age of 30. No studies have investigated mortality associated with subthreshold levels of ADHD symptoms. Our aim was to analyze mortality in a perinatal risk cohort of 46-year-old adults with childhood ADHD (cADHD) and milder childhood attention problems (including hyperactivity and inattention; cAP) compared with a group with similar birth risks but no or low levels of childhood ADHD symptoms (Non-cAP). Causes of death obtained from a national register were examined. METHODS: Mortality was analyzed with Cox proportional hazard models for all-cause mortality, cause-specific mortality (natural and unnatural causes), and age-specific mortality (under and over age 30). All models were adjusted with gender. The total n in the study was 839 (cADHD n = 115; cAP n = 216; Non-cAP n = 508). RESULTS: By the age of 46, 11 (9.6%) deaths occurred in the cADHD group, 7 (3.2%) in the cAP group, and 20 (3.9%) in the Non-cAP group. The cADHD group had the highest mortality risk (adjusted hazard ratio = 2.15; 95% CI 1.02, 4.54). Mortality was not elevated in the cAP group (adjusted hazard ratio = 0.72; 95% CI .30, 1.72). Mortality in the cADHD group was mainly attributed to unnatural causes of death (adjusted hazard ratio = 2.82; 95% CI 1.12, 7.12). The mortality risk in the cADHD group was sixfold before age 30 (adjusted hazard ratio = 6.20; 95% CI 1.78, 21.57). CONCLUSIONS: Childhood ADHD was associated with a twofold risk of premature death by the age of 46 in this prospective longitudinal cohort study. Our results corroborate previous findings and the morbidity of ADHD. Subthreshold levels of childhood ADHD symptoms were not linked to increased mortality. Our results suggest that mortality risk is higher in young than middle adulthood. Future studies should examine mortality associated with ADHD in different ages in adulthood to identify those in greatest risk of premature death.

DARE to move: feasibility study of a novel dance-based rehabilitation method in severe traumatic brain injury.

Objective: Dance is a versatile and multimodal rehabilitation method, which may be useful also in traumatic brain injury (TBI) rehabilitation. Here, we assessed the feasibility and preliminary effects of a novel dance-based intervention called Dual-Assisted Dance Rehabilitation (DARE).Method: This is a feasibility study with a cross-over design where 11 persons with severe/extremely severe TBI received a 12-week (2 times/week) DARE program. Motor and neuropsychological tests and questionnaires measuring mood, executive functions, and quality of life were performed at baseline, 3-month, and 6-month stage. Self-perceived benefits were assessed with a post-intervention questionnaire.Results: Acceptability of and adherence to DARE were encouraging: 91% were fully consistent with protocol, and adherence to DARE sessions was 83-100%. Pre-post treatment effects sizes were medium-large for self-reported depression (BDI-II: d = 1.19-1.74) and executive deficits (BRIEF-A: d = 0.43-1.09) and for test-assessed trunk movement control (TIS: d = 0.47-0.76) and cognitive functioning (WAIS-IV subtests: d = 0.34-0.89). Other outcome measures did not show similar positive effect sizes. Self-perceived benefits were largest for mobility and cognition.Conclusion: Dance-based rehabilitation is a feasible and promising method in severe TBI and its efficacy should be assessed with a larger clinical trial.

Associations between Prospective and Retrospective Subjective Memory Complaints and Neuropsychological Performance in Older Adults: The Finger Study.

OBJECTIVES: Subjective memory complaints (SMCs) are among the key concerns in the elderly, but their role in detecting objective cognitive problems is unclear. The aim of this study was to clarify the association between SMCs (both prospective and retrospective memory complaints) and neuropsychological test performance in older adults at risk of cognitive decline. METHODS: This investigation is part of the FINGER project, a multicenter randomized controlled trial aiming at preventing cognitive decline in high-risk individuals. The cognitive assessment of participants was conducted at baseline using a modified neuropsychological test battery (NTB). SMCs were evaluated with the Prospective and Retrospective Memory Questionnaire (PRMQ) in a sub-sample of 560 participants (mean age, 69.9 years). RESULTS: Having more prospective SMCs was associated with slower processing speed, but not with other NTB domains. Retrospective SMCs were linked to poorer function on NTB total score, processing speed, and memory. Executive function domain was not associated with any PRMQ ratings. Depressive symptoms and poor quality of life diluted the observed associations for NTB total score and memory. However, the association between PRMQ and processing speed remained even after full adjustments. CONCLUSIONS: Our results indicate that self-reported memory problems, measured with PRMQ, are associated with objectively measured cognitive performance. Such complaints in healthy elderly people also seem to reflect reduced mental tempo, rather than memory deficits. Slowing of processing speed may thus be negatively related to memory self-efficacy. It is also important to consider affective factors among those who report memory problems. (JINS, 2018, 24, 1099-1109).

Recovery of gestures for persons with severe non-fluent aphasia and limb apraxia: A long-term follow-up study.

Persons with severe non-fluent aphasia would benefit from using gestures to substitute for their absent powers of speech. The use of gestures, however, is challenging for persons with aphasia and concomitant limb apraxia. Research on the long-term recovery of gestures is scant, and it is unclear whether gesture performance can show recovery over time. This study evaluated the recovery of emblems and tool use pantomimes of persons with severe non-fluent aphasia and limb apraxia after a left hemisphere stroke. The Florida Apraxia Screening Test-Revised (FAST-R) was used for measurements. The test includes 30 gestures to be performed (i) after an oral request, (ii) with the aid of a pictorial cue, or (iii) as an imitation. The gestures were rated on their degree of comprehensibility. The comprehensibility of gestures after an oral request improved significantly in five out of seven participants between the first (1-3 months after the stroke) and the last (3 years after) examination. Improvement continued for all five in the period between six months and three years. The imitation model did improve the comprehensibility of gestures for all participants, whereas the pictorial cue did so just slightly. The skill of producing gestures can improve even in the late phase post-stroke. Because of this potential, we suggest that gesture training should be systematically included in the rehabilitation of communication for persons with severe non-fluent aphasia.

Brain magnetic resonance imaging findings six months after critical COVID-19: A prospective cohort study.

BACKGROUND: COVID-19 patients suffered from neurological symptoms in the acute phase. Whether this led to long-term consequences was unknown. We studied long-term brain MRI findings in ICU-treated COVID-19 patients and compared them with findings in groups with less severe acute disease. MATERIALS AND METHODS: In this prospective cohort study, 69 ICU-treated, 46 ward-treated, and 46 home-isolated patients, as well as 53 non-COVID-19 controls, underwent brain MRI six months after acute COVID-19. Plasma neurofilament light chain (NfL), a biomarker of neuroaxonal injury, was measured simultaneously. RESULTS: Ischaemic infarctions existed in 5.8% of ICU-treated patients. Cerebral microbleeds (CMBs) existed in 27 (39.1%) ICU-treated, 13 (28.3%) ward-treated, 8 (17.4%) home-isolated COVID-19 patients, and 12 (22.6%) non-COVID controls. Patients with CMBs were older (p < 0.001), had a higher level of plasma NfL (p = 0.003), and higher supplementary oxygen days (p < 0.001). In multivariable analysis, age (OR 1.06, 95% CI 1.02-1.09) and supplementary oxygen days (OR 1.07, 95% CI 1.02-1.13) were associated with CMBs. The ICU group showed prevalent distribution of CMBs in deep regions. CONCLUSION: Age and supplementary oxygen days were independently associated with CMBs; COVID-19 status showed no association. Accumulation of risk factors in the ICU group may explain the higher prevalence of CMBs. TRIAL REGISTRATION: ClinicalTrials.govNCT04864938, registered February 9, 2021.

Childhood motor difficulties and cognitive impairment in midlife: A 40-year cohort study.

OBJECTIVE: We aimed to examine the association of childhood motor difficulties (MD) with cognitive impairment in midlife. METHOD: We studied 357 participants from a cohort born in 1971-1975. At age 9, they had completed the Test of Motor Impairment, which classified them into three groups: childhood MD (cMD), borderline cMD (bcMD), or no cMD. Participants with attention-deficit/hyperactivity disorder were excluded. At age 40, participants comprised 18 (5.0%) with cMD, 43 (12.0%) with bcMD, and 296 (82.9%) with no cMD. They underwent neuropsychological assessment covering six domains: executive functions, processing speed, attention and working memory, learning and memory, verbal symbolic abilities, and visuoperceptual and visuospatial abilities. A participant was considered to have an impairment if their performance was in the 15th percentile of a normative group. RESULTS: Participants with cMD were more likely than those with no cMD to have an impairment in executive functions (OR = 6.73, p < .01), processing speed (OR = 3.85, p < .05), attention and working memory (OR = 4.79, p < .01), and a cross-domain impairment (OR = 3.62, p < .01). These differences remained significant after adjusting for parents' occupation, sex, and low birth weight and after multiple imputation. No consistent difference emerged between participants with bcMD and no cMD. CONCLUSIONS: Childhood MD are associated with midlife cognitive impairment, which underscores their long-term implications. In the neuropsychological assessment of an adult patient, information on childhood motor development is of value. The assessment may help adapt the patient's physical or occupational therapy to the patient's cognitive profile. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Motor difficulties from childhood to midlife: A 40-year cohort study.

BACKGROUND: There are few studies of the persistence of childhood motor difficulties (MD) into adulthood. AIMS: To investigate the association of childhood MD with motor skills and body mass index (BMI) in midlife. METHODS AND PROCEDURES: We studied 324 adults aged 40 from a cohort born in 1971-1974. At age 9, they had undergone the Test of Motor Impairment, used to classify them into groups: childhood MD (cMD), borderline cMD (bcMD), or no cMD. At age 40, participants comprised 23 with cMD, 47 with bcMD, and 254 with no cMD. Participants completed motor tests of balance, manual dexterity, and visuomotor speed, followed by recording of their BMI. OUTCOMES AND RESULTS: At age 40, the cMD group performed worse than the no-cMD group on all motor tests (p < .001-.008). The bcMD group had slower visuomotor speed than the no-cMD group (p = .025). The groups differed in BMI (p = .002). Having cMD was associated with obesity in midlife (p < .001). After adjusting for sex, childhood socioeconomic status, and BMI at age 9, both cMD and bcMD were associated with obesity in midlife (p = .015). CONCLUSIONS AND IMPLICATIONS: Childhood MD are associated with poor motor skills, overweight, and obesity in midlife. This emphasises the importance of early intervention and follow-up when a child exhibits MD. WHAT THIS PAPER ADDS: This prospective longitudinal study presents novel evidence that individuals with a history of comprehensively and objectively assessed childhood motor difficulties (MD) have worse motor skills and a higher risk of obesity in midlife than do those with no childhood MD. There is a growing literature on adults with developmental coordination disorder or a history of MD. There is, however, a scarcity of longitudinal studies of childhood MD that continue beyond early adulthood, into midlife. In a systematic search, we could identify only one longitudinal study of objectively measured childhood MD with a reassessment of motor skills in those same participants in adulthood, and no study with a reassessment after age 20. Furthermore, longitudinal studies of the association of comprehensively and objectively assessed childhood MD with BMI in midlife have been lacking.

Health-related quality of life after surviving intensive care for COVID-19: a prospective multicenter cohort study.

In survivors of severe coronavirus disease 2019 (COVID-19) incomplete mental and physical recovery may considerably impact daily activities and health-related quality of life (HRQoL). HRQoL can be evaluated with the RAND-36 questionnaire, a multidimensional instrument that assesses physical and mental aspects of health in eight dimensions. The objective was to investigate HRQoL in intensive care patients previously treated for COVID-19 at three Nordic university hospitals, in a prospective multi-center cohort study. HRQoL was measured using RAND-36, 3-9 months after discharge from intensive care units (ICU). One hospital performed a second follow-up 12 months after discharge. A score under the lower limit of the 95% confidence interval in the reference cohorts was considered as significantly reduced HRQoL. We screened 542 and included 252 patients. There was more than twice as many male (174) as female (78) patients and the median age was 61 (interquartile range, IQR 52-69) years. Hypertension was the most common comorbidity observed in 132 (52%) patients and 121 (48%) patients were mechanically ventilated for a median of 8 (IQR 4-14) days. In RAND-36 physical functioning, physical role functioning, general health (p < 0.001 for all) and social functioning (p < 0.05) were below reference, whereas bodily pain, emotional role functioning and mental health were not. In a time-to-event analysis female sex was associated with a decreased chance of reaching the reference HRQoL in the physical function, bodily pain and mental health dimensions. Higher body mass index was found in the physical functioning dimension and hypertension in the physical functioning, vitality and social functioning dimensions. Similar results were seen for diabetes mellitus in general health, vitality and mental health dimensions, as well as pulmonary illness in the physical role functioning dimension and psychiatric diagnosis in the social functioning dimension. Mechanical ventilation was associated with a decreased likelihood of achieving reference HRQoL in the bodily pain and physical functioning dimensions. Patients treated in an ICU because of COVID-19 had lower HRQoL 3-9 months after ICU discharge than 95% of the general population. Physical dimensions were more severely affected than mental dimensions. Female sex and several comorbidities were associated with a slower rate of recovery.Study registration: clinicaltrials.gov: NCT04316884 registered on the 13th of March 2020, NCT04474249 registered on the 29th of June 2020 and NCT04864938 registered on the 4th of April 2021.

Associations of subjective and objective cognitive functioning after COVID-19: A six-month follow-up of ICU, ward, and home-isolated patients.

Background: Subjective and objective cognitive dysfunction are reported after COVID-19 but with limited data on their congruence and associations with the severity of the acute disease. The aim of this cohort study is to describe the prevalence of subjective and objective cognitive dysfunction at three and six months after COVID-19 and the associations of subjective cognitive symptoms and psychological and disease-related factors. Methods: We assessed a cohort of 184 patients at three and six months after COVID-19: 82 patients admitted to the Intensive Care Unit (ICU), 53 admitted to regular hospital wards, and 49 isolated at home. A non-COVID control group of 53 individuals was included. Demographic and clinical data were collected. Subjective cognitive symptoms, objective cognitive impairment, and depressive and post-traumatic stress disorder (PTSD) symptoms were assessed. Results: At six months, subjective cognitive impairment was reported by 32.3% of ICU-treated, 37.3% of ward-treated, and 33.3% of home-isolated patients and objective cognitive impairment was observed in 36.1% of ICU-treated, 34.7% of ward-treated, and 8.9% of home-isolated patients. Subjective cognitive symptoms were associated with depressive and PTSD symptoms and female sex, but not with objective cognitive assessment or hospital metrics. Conclusions: One-third of COVID-19 patients, regardless of the acute disease severity, reported high levels of subjective cognitive dysfunction which was not associated with results from objective cognitive screening but with psychological and demographic factors. Our study stresses the importance of thorough assessment of patients reporting long-term subjective symptoms, screening for underlying mental health related factors such as PTSD or depression.

C9orf72 hexanucleotide repeat allele tagging SNPs: Associations with ALS risk and longevity.

C9orf72 hexanucleotide repeat expansion is a common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The C9orf72 locus may harbor residual risk outside the hexanucleotide repeat expansion, but the evidence is conflicting. Here, we first compared 683 unrelated amyotrophic lateral sclerosis cases and 3,196 controls with Finnish ancestry to find best single nucleotide polymorphisms that tag the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles. Rs2814707 was the best tagging single nucleotide polymorphisms for intermediate-length alleles with ≥7 repeats (p = 5 × 10-307) and rs139185008 for the hexanucleotide repeat expansion (p = 7 × 10-114) as well as alleles with ≥20 repeats. rs139185008*C associated with amyotrophic lateral sclerosis after removing cases with the hexanucleotide repeat expansion, especially in the subpopulation homozygous for the rs2814707*T (p = 0.0002, OR = 5.06), which supports the concept of residual amyotrophic lateral sclerosis risk at the C9orf72 haplotypes other than the hexanucleotide repeat expansion. We then leveraged Finnish biobank data to test the effects of rs2814707*T and rs139185008*C on longevity after removing individuals with amyotrophic lateral sclerosis / frontotemporal dementia diagnoses. In the discovery cohort (n = 230,006), the frequency of rs139185008*C heterozygotes decreased significantly with age in the comparisons between 50 and 80 years vs. >80 years (p = 0.0005) and <50 years vs. >80 years (p = 0.0001). The findings were similar but less significant in a smaller replication cohort (2-sided p = 0.037 in 50-80 years vs. >80 years and 0.061 in <50 years vs. >80 years). Analysis of the allele frequencies in 5-year bins demonstrated that the decrease of rs139185008*C started after the age of 70 years. The hexanucleotide repeat expansion tagging single nucleotide polymorphisms decreasing frequency with age suggests its' association with age-related diseases probably also outside amyotrophic lateral sclerosis / frontotemporal dementia.

Project DyAdd: classical eyeblink conditioning in adults with dyslexia and ADHD.

In this study of the project DyAdd (Adult Dyslexia and Attention Deficit Disorder in Finland), classical eyeblink conditioning (EBC) was investigated in both delay and trace paradigms in adults (18-55 years) with dyslexia (n = 37), attention deficit-hyperactivity disorder (ADHD; n = 21), their comorbid combination (n = 8), and healthy controls (n = 35). In addition, the profiles of three participants with a rare autosomal dominant cerebellar disease were assessed (episodic ataxia type 2, EA-2). We found that participants with dyslexia were overall slower learners than controls in eyeblink conditioning. Further, they were the only group that had a reduced number of CRs in mediotemporal-dependent trace paradigm compared to the more cerebellum-dependent delay paradigm. Second, ADHD was found to be related to larger CR amplitude. Third, those with a comorbid condition learned faster and manifested CRs that were not well timed. Fourth, the cerebellar patients showed nearly no conditioning at all. Correlations between EBC and various neuropsychological domains (phonological processing, reading, spelling, arithmetic, executive functions, attention, and fine motor control) over all participants resulted in significant relations only for the delay paradigm: Increased amount of reading errors related with later peak latency and increased amount of self-corrections in fine motor control related with larger response magnitude. Within those who conditioned, relations emerged only for the trace paradigm: better spelling was related to larger response magnitude. These results do not lend support to the cerebellar hypothesis of dyslexia. On the contrary, dyslexia in its pure form seems to be related to a relative dysfunction of a larger hippocampal-cerebellar network. Further, larger responses in the ADHD group are suggested to result from their lowered responding threshold.

Project DyAdd: visual attention in adult dyslexia and ADHD.

In this study of the project DyAdd, three aspects of visual attention were investigated in adults (18-55years) with dyslexia (n=35) or attention deficit/hyperactivity disorder (ADHD, n=22), and in healthy controls (n=35). Temporal characteristics of visual attention were assessed with Attentional Blink (AB), capacity of visual attention with Multiple Object Tracking (MOT), and spatial aspects of visual attention with Useful Field of View (UFOV) task. Results showed that adults with dyslexia had difficulties performing the AB and UFOV tasks, which were explained by an impaired ability to process dual targets, longer AB recovery time, and deficits in processing rapidly changing visual displays. The ADHD group did not have difficulties in any of the tasks. Further, performance in the visual attention tasks predicted variation in measures of phonological processing and reading when all of the participants were considered together. Thus, difficulties in tasks of visual attention were related to dyslexia and variation of visual attention had a role in the reading ability of the general population.

Status of Clinical Neuropsychology Training in Finland.

This paper provides information on different training models within clinical neuropsychology in Finland. Systematic specialization training program began in Finland in 1983. It was first organized mainly by the Finnish Neuropsychological Society and since 1997 by the Finnish universities. At present, close to 400 clinical neuropsychologists have completed the training. The number of professionals still does not cover the needs of the country (population 5.5 million, area 338,440 km2), and geographical disparities are a constant concern. The training models in Finland have changed over the years and will continue to evolve. Specialization training can be organized by national societies or by universities. It can lead to an academic degree or a diploma. It can be linked to doctoral studies or form a parallel track. Financial model can involve student fees or be governed by ministries (such as the Ministry of Education or Ministry of Health). This paper describes and compares different strategies in education that have impact on the output of professionals. One model does not fit all, or even one country at all times. The strategies of the stakeholder ministries can change over time. The experiences from Finland can be useful for other countries that are developing their models. The estimated need of practitioners and the educational resources including the available financial models for training differ between countries. The guiding principles in specialist training should focus on the advanced competencies expected from the neuropsychologist when entering the profession.

No Clinically Relevant Memory Effects in Perinatal Hyperglycemia and Hypoglycemia: A 40-Year Follow-Up of a Small Cohort.

Maternal diabetes mellitus in pregnancy is associated with impairments in memory functions of the offspring in childhood and adolescence but has not been studied in adulthood. The association of perinatal hypoglycemia with memory has not been studied in adulthood either. The combined sequelae of these two risk factors have not been directly compared. We studied general cognitive ability and memory functions in a prospective follow-up of a cohort born in 1971 to 1974. The sample included participants exposed to prenatal hyperglycemia (n = 24), perinatal hypoglycemia (n = 19), or both (n = 7). It also included controls with no early risks (n = 82). We assessed the participants' Intelligence quotient (IQ), working memory, and immediate and delayed recall of both verbal and visual material at the age of 40. We did not find significant differences in IQ or the memory tests between the groups. We did identify an interaction (p = 0.03) of the early risk with the type of digit span task: compared to the controls, the participants exposed to perinatal hypoglycemia had a larger difference between the forward digit span, a measure of attention, and the backward digit span, a measure of working memory processing (p = 0.022). The interaction remained significant when birth weight was controlled for (p = 0.026). Thus, in this small cohort, prenatal hyperglycemia, perinatal hypoglycemia, and their combination appeared relatively benign disorders. The association of these conditions with neurocognitive impairments in adulthood remains unconfirmed. The significance of the working memory difference needs to be verified with a larger sample.

Core Competencies in Clinical Neuropsychology as a Training Model in Europe.

The multitude of training models and curricula for the specialty of clinical neuropsychology around the world has led to organized activities to develop a framework of core competencies to ensure sufficient expertise among entry-level professionals in the field. The Standing Committee on Clinical Neuropsychology of the European Federation of Psychologists' Associations is currently working toward developing a specialty certification in clinical neuropsychology to establish a cross-national standard against which to measure levels of equivalency and uniformity in competence and service provision among professionals in the field. Through structured interviews with experts from 28 European countries, we explored potential areas of core competency. Specifically, questions pertained to the perceived importance of a series of foundational, functional, and other competencies, as well as current training standards and practices, and optimal standards. Our findings revealed considerable agreement (about three quarters and above) on academic and clinical training, despite varied actual training requirements currently, with fewer respondents relegating importance to training in teaching, supervision, and research (a little over half), and even fewer to skills related to management, administration, and advocacy (fewer than half). European expert clinical neuropsychologists were in agreement with previous studies (including those conducted in the United States, Australia, and other countries) regarding the importance of sound theoretical and clinical training but management, administrative, and advocacy skills were not central to their perspective of a competent specialist in clinical neuropsychology. Establishing a specialty certificate in clinical neuropsychology based on core competencies may enable mobility of clinical neuropsychologists across Europe, and, perhaps, provide an impetus for countries with limited criteria to reconsider their training requirements and harmonize their standards with others.

Shortening of Saccades as a Possible Easy-to-Use Biomarker to Detect Risk of Alzheimer's Disease.

BACKGROUND: Wide-ranging functional defects in eye movements have been reported in Alzheimer's disease (AD) dementia. The detection of abnormal eye movements and reading problems may identify persons at risk of AD when clear clinical symptoms are lacking. OBJECTIVE: To examine whether computer-based eye-tracking (ET) analysis of King-Devick (KD) test results differentiates cognitively healthy persons from persons with minor problems in cognitive testing or diagnosed mild AD. METHODS: We recruited 78 participants (57 non-demented, 21 with mild AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating (CDR) interview. The non-demented participants were further divided into control (normal CERAD subtests, mean MMSE = 28) and objective mild cognitive impairment (MCI; decline in at least one CERAD memory score, mean MMSE = 27) groups. The KD reading test was performed using computer-based ET. The total time used for the reading test, errors made, fixation and saccade durations, and saccade amplitudes were analyzed. RESULTS: We found significant differences between the control, objective MCI, and AD groups in regard to the mean saccade amplitude (3.58, 3.33, and 3.21 ms, respectively, p < 0.03) and duration (27.1, 25.3, and 24.8 ms, respectively, p < 0.05). The KD error scores in the AD group differed significantly (p < 0.01) from the other groups. CONCLUSION: Computed ET analysis of the KD test may help detect persons with objective MCI early when clear clinical symptoms are lacking. The portable device for ET is easy to use in primary health care memory clinics.