This study compared brain activations during unpaced rhythmic finger tapping in 12-year old children with those of adults. The subject pressed a button at a pace initially indicated by a metronome (12 consecutive tones) and then continued for 16 seconds of unpaced tapping to provide an assessment of his/her ability to maintain a steady rhythm. In particular, the analyses focused on the superior vermis of the cerebellum, which is known to play a key role in timing.

12 adults and 12 children performed this rhythmic finger tapping task in a 3T scanner. Whole-brain analyses were performed in Brain Voyager with a random effects analysis of variance using the general linear model. A dedicated cerebellar atlas was used to localise cerebellar activations.

As in adults, unpaced rhythmic finger tapping in children showed activations in the primary motor cortex, premotor cortex, and cerebellum. However, overall activation was different in that adults showed much more deactivation in response to the task, particularly in the occipital and frontal cortex. The other main differences were additional recruitment of motor and premotor areas in children compared to adults along with increased activity in the vermal region of the cerebellum.

These findings suggest that the timing component of the unpaced rhythmic finger tapping task is less efficient and automatic in children, who needed to recruit the superior vermis more intensively to maintain the rhythm, even though they performed somewhat more poorly than the adults.

Background

Down syndrome appears to be associated with a virtually certain risk of fibrillar amyloid-β (Aβ) pathology by the age of 40 and a very high risk of dementia at older ages. The positron emission tomography (PET) ligand florbetapir F18 has been shown to characterize fibrillar Aβ in the living human brain and to provide a close correlation with subsequent Aβ neuropathology in individuals proximate to and after the end of life. The extent to which the most frequently used PET ligands can be used to detect fibrillar Aβ in patients with Down syndrome remains to be determined.

Objectives

To characterize PET estimates of fibrillar Aβ burden in a Down syndrome patient very close to the end of life and to compare them with neuropathologic assessment made after his death.

Design/Methods

With the family’s informed consent, florbetapir PET was used to study a 55-year-old Down syndrome patient with Alzheimer disease near the end of life; his brain was donated for neuropathologic assessment when he died 14 days later. Visual ratings of cerebral florbetapir uptake were performed by trained readers who were masked to the patient’s diagnosis as part of a larger study, and an automated algorithm was used to characterize regional-to-cerebellar standard uptake value ratios in 6 cerebral regions of interest. Neuropathologic assessments were performed masked to the patient’s diagnosis or PET measurements.

Results

Visual ratings and automated analyses of the PET image revealed a heavy fibrillar Aβ burden in cortical, striatal, and thalamic regions, similar to that reported for patients with late-onset Alzheimer disease. This matched neuropathologic findings of frequent neuritic and diffuse plaques, as well as frequent amyloid angiopathy, except for neuropathologically demonstrated frequent cerebellar diffuse plaques and amyloid angiopathy that were not detected by the PET scan.

Conclusions

Florbetapir PET can be used to detect increased cerebral-to-cerebellar fibrillar Aβ burden in a Down syndrome patient with Alzheimer disease, even in the presence of frequent amyloid angiopathy and diffuse plaques in the cerebellum. Additional studies are needed to determine the extent to which PET could be used to detect and to track fibrillar Aβ and to evaluate investigational Aβ-modifying treatments in the presymptomatic and symptomatic stages of Alzheimer disease.

Background: Prenatal exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) has been associated with impaired performance on attention tasks in previous studies, but the extent to which these cognitive deficits translate into behavioral problems in the classroom and attention deficit/hyperactivity disorder (ADHD) remains unknown. By contrast, lead (Pb) exposure in childhood has been associated with ADHD and disruptive behaviors in several studies.

Objectives: In this study we examined the relation of developmental exposure to MeHg, PCBs, and Pb to behavioral problems at school age in Inuit children exposed through their traditional diet.

Methods: In a prospective longitudinal study conducted in the Canadian Arctic, exposure to contaminants was measured at birth and at school age. An assessment of child behavior (n = 279; mean age = 11.3 years) was obtained from the child’s classroom teacher on the Teacher Report Form (TRF) from the Child Behavior Checklist, and the Disruptive Behavior Disorders Rating Scale (DBD).

Results: Cord blood mercury concentrations were associated with higher TRF symptom scores for attention problems and DBD scores consistent with ADHD. Current blood Pb concentrations were associated with higher TRF symptom scores for externalizing problems and with symptoms of ADHD (hyperactive-impulsive type) based on the DBD.

Conclusions: To our knowledge, this study is the first to identify an association between prenatal MeHg and ADHD symptomatology in childhood and the first to replicate previously reported associations between low-level childhood Pb exposure and ADHD in a population exposed to Pb primarily from dietary sources.

Background

Normal pressure hydrocephalus (NPH) is considered potentially treatable with the placement of a cerebrospinal fluid (CSF) shunt. Yet, the procedure has had variable success, particularly with respect to improving the cognitive impairment in NPH. The presence of neurologic co-morbidities, particularly Alzheimer's Disease (AD), may contribute to shunt responsiveness. Uncovering the extent to which AD and NPH co-occur has implications for diagnosis and treatment of NPH. Autopsy studies of patients with NPH during life would elucidate the frequency of such co-morbidities.

Methods

We conducted a search of the Sun Health Research Institute Brain Donation Program database between 1/1/1997 and 4/1/09 to identify all cases with neuropathologic evidence of dementia as well as those cases of clinically diagnosed NPH. We reviewed the medical records and brain findings of each NPH case.

Results

Of the 761 cases autopsied over the study interval, 563 cases were found to have neuropathological evidence meeting criteria for a dementing illness. AD was found exclusively in 313/563 (56%) cases with 94/563 cases having a secondary diagnosis of dementia.

We identified 9/761 cases with a clinical diagnosis of NPH, all nine cases were among the 563 cases with neuropathology of dementing illness at autopsy, representing 1.6% (9/563). Upon review of brain autopsy reports, 8/9 (89%) cases were found to have AD and 1/9 (11%) had progressive supranuclear palsy. Review of the medical records of the nine NPH cases revealed the following clinical co-morbidities: 5/9 with AD; 1/9 with Parkinson's Disease (PD); 1/9 with Mild Cognitive Impairment (MCI); 1/9 with seizure disorder.

Conclusions

Given the findings of our study, we support the AD-NPH theory and posit that AD is a common pathological co-morbidity in the setting of NPH and may preclude cognitive improvement post-shunt placement. This may have influence on selection of cases for shunting in the future.

Objectives

Use three-dimensional (3D) facial laser scanned images from children with fetal alcohol syndrome (FAS) and controls to develop an automated diagnosis technique that can reliably and accurately identify individuals prenatally exposed to alcohol.

Methods

A detailed dysmorphology evaluation, history of prenatal alcohol exposure, and 3D facial laser scans were obtained from 149 individuals (86 FAS; 63 Control) recruited from two study sites (Cape Town, South Africa and Helsinki, Finland). Computer graphics, machine learning, and pattern recognition techniques were used to automatically identify a set of facial features that best discriminated individuals with FAS from controls in each sample.

Results

An automated feature detection and analysis technique was developed and applied to the two study populations. A unique set of facial regions and features were identified for each population that accurately discriminated FAS and control faces without any human intervention.

Conclusion

Our results demonstrate that computer algorithms can be used to automatically detect facial features that can discriminate FAS and control faces.

Background

Although an extensive literature has documented a broad range of cognitive performance deficits in children with prenatal alcohol exposure, little is known about how the neurophysiological processes underlying these deficits may be affected. Event-related potentials (ERPs), which reflect task-specific changes in brain electrical activity, provide a method for examining multiple constituents of cognitive processing at the neural level.

Methods

We recorded ERPs in 217 children from Inuit communities in Arctic Quebec (M age = 11.3 yr) during two different tasks—Go/No-go response inhibition and continuous recognition memory. Children were classified as either alcohol-exposed (ALC) or controls (CON) depending on whether the mother reported binge drinking during pregnancy.

Results

Both groups performed comparably in terms of accuracy and reaction time on the tasks, and both tasks elicited the expected effects on ERPs when responses were compared across conditions. However, the ALC group showed slower P2 latencies on Go/No-go, suggesting an altered neurophysiological response associated with initial visual processing of the stimuli. On the memory task, the ALC group showed reduced FN400 amplitude to new items, known as the familiarity effect, and reduced amplitude for the late positive component, possibly reflecting impairment in memory retrieval.

Conclusions

These findings show that, even in tasks in which alcohol-exposed children exhibit behavioral performance that is comparable to controls, fetal alcohol exposure is associated with altered neurophysiological processing of response inhibition and recognition memory. The data suggest that fetal alcohol exposure is associated with reduced efficiency in the initial extracting of the meaning of a stimulus, reduced allocation of attention to the task, and poorer conscious, explicit recognition memory processing.

Background

Poor arithmetic performance is among the most sensitive outcomes associated with prenatal alcohol exposure and is also common in individuals with attention deficit hyperactivity disorder (ADHD). We hypothesized that prenatal alcohol exposure would be associated with deficits in the most fundamental aspects of number processing, representation of quantity and distance; whereas ADHD would be associated with deficits in calculation, the form of number processing most dependent on attention and memory.

Methods

262 inner-city, African American adolescents, who had been evaluated prospectively for prenatal alcohol exposure and ADHD, were assessed on a number processing test comprised of 7 subtests.

Results

More heavily alcohol-exposed adolescents were four times more likely to meet diagnostic criteria for ADHD than those whose mothers abstained from alcohol use during pregnancy. Two dimensions of number processing were identified in a factor analysis—magnitude comparison and calculation. As hypothesized, prenatal alcohol exposure was more strongly related to the former; ADHD, to the latter. Moreover, the relation of prenatal alcohol to calculation was fully mediated by magnitude comparison, whereas the relation of ADHD to calculation was mediated by IQ but not by magnitude comparison.

Conclusion

These data confirm findings from previous studies identifying arithmetic as a particularly sensitive developmental endpoint for prenatal alcohol exposure. Whereas difficulties with arithmetic in ADHD are mediated by domain-general deficits in overall cognitive ability, fetal alcohol-related arithmetic difficulties are mediated primarily by a specific deficit in the core quantity system involving the ability to mentally represent and manipulate number. These data suggest that different interventions are likely to be effective for remediating arithmetic problems in children with prenatal alcohol exposure than in non-exposed children with ADHD.

Objective

Compare the frequency of REM sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS) in Parkinson’s disease (PD), restless legs syndrome (RLS), essential tremor (ET), and control subjects.

Methods

Subjects enrolled in a longitudinal clinicopathologic study, and when available an informant, completed the Mayo Sleep Questionnaire, which asks “Have you ever been told that you act out your dreams?”, and the Epworth Sleepiness Scale (ESS).

Results

Probable RBD (based on informant response to the questionnaire) was much more frequent in PD (34/49, 69%, p<0.001) than in RLS (6/30, 20%), ET (7/53, 13%), or control subjects (23/175, 13%), with an odds ratio of 11 for PD compared to controls. The mean ESS and the number of subjects with an ESS ≥ 10 was higher in PD (29/60, 48%, p<0.001) and RLS (12/39, 31%, p<0.001) compared with ET (12/93, 13%) and Controls (34/296, 11%).

Conclusions

Probable RBD is much more frequent in PD with no evidence to suggest an increase in either RLS or ET. Given the evidence that RBD is a synucleinopathy, the lack of an increased frequency of RBD in subjects with ET or RLS suggests the majority of ET and RLS subjects are unlikely to be at increased risk for developing PD.

Background

Alcohol consumption during pregnancy, a known teratogen often associated with drug use and smoking, is a well-known public health concern.

Aim

This study provides prevalence data for alcohol, smoking, and illicit drug use before, during, and after pregnancy among Inuit. Factors associated with alcohol use are also identified.

Methods

248 Inuit women from Arctic Quebec were interviewed at mid-pregnancy, and at 1 and 11 months postpartum to provide descriptive data on smoking, alcohol, and drug use during pregnancy, and the year before and after pregnancy. Sociodemographic and family characteristics potentially associated with alcohol use were documented.

Results

92% of the women reported smoking and 61% reported drinking during pregnancy. Episodes of binging during pregnancy were reported by 62% of the alcohol users, which corresponds to 38% of pregnant women. 36% of the participants reported using marijuana during pregnancy. Alcohol use and binge drinking during pregnancy were more likely to be reported by women who lived in less crowded houses, had a better knowledge of a second language, drank alcohol more often and in larger amounts prior to pregnancy, and used illicit drugs. Binge drinkers were more likely to be single women and to have had fewer previous pregnancies. Postpartum distress and violence were more likely to be experienced by women who used alcohol during pregnancy. Binge drinking during pregnancy was best predicted by drinking habits before pregnancy, maternal symptoms of depression, the use of illicit drugs during pregnancy and the number of young children living with the mother.

Conclusions

These results confirm that alcohol is a major risk factor to maternal and child health in this population, underscoring the need for culturally relevant and effective prevention programs.

Identification of children with fetal alcohol spectrum disorders (FASD) is difficult because information regarding prenatal exposure is often lacking, a large proportion of affected children do not exhibit facial anomalies, and no distinctive behavioral phenotype has been identified. Castellanos and Tannock have advocated going beyond descriptive symptom-based approaches to diagnosis to identify biomarkers derived from cognitive neuroscience. Classical eyeblink conditioning and magnitude comparison are particularly promising biobehavioral markers of FASD—eyeblink conditioning because a deficit in this elemental form of learning characterizes a very large proportion of alcohol-exposed children; magnitude comparison because it is a domain of higher order cognitive function that is among the most sensitive to fetal alcohol exposure. Because the neural circuitry mediating both these biobehavioral markers is well understood, they have considerable potential for advancing understanding of the pathophysiology of FASD, which can contribute to development of treatments targeted to the specific deficits that characterize this disorder.

Background: Lead (Pb) and polychlorinated biphenyls (PCBs) are neurotoxic contaminants that have been related to impairment in response inhibition.

Objectives: In this study we examined the neurophysiological correlates of the response inhibition deficits associated with these exposures, using event-related potentials (ERPs) in a sample of school-age Inuit children from Arctic Québec exposed through their traditional diet.

Methods: In a prospective longitudinal study, we assessed 196 children (mean age, 11.3 years) on a visual go/no-go response inhibition paradigm. Pb, PCB, and mercury (Hg) concentrations were analyzed in cord and current blood samples. Hierarchical multiple regression analyses were conducted to examine the associations of contaminant levels to go/no-go performance (mean reaction time, percent correct go, percent correct no-go) and five ERPs [N2, P3, error-related negativity, error positivity (Pe), and correct response positivity (Pc)] after control for confounding variables.

Results: Current blood Pb concentrations were associated with higher rates of false alarms and with decreased P3 amplitudes to go and no-go trials. Current plasma PCB-153 concentrations were associated with slower reaction times and with reduced amplitudes of the Pe and Pc response-related potentials. Hg concentrations were not related to any outcome on this task but showed significant interactions with other contaminants on certain outcomes.

Conclusions: These results suggest that Pb exposure during childhood impairs the child’s ability to allocate the cognitive resources needed to correctly inhibit a prepotent response, resulting in increased impulsivity. By contrast, postnatal PCB exposure appears to affect processes associated with error monitoring, an aspect of behavioral regulation required to adequately adapt to the changing demands of the environment, which results in reduced task efficiency.

Background

Differentiating amnestic mild cognitive impairment (aMCI) from normal cognition is difficult in clinical settings. Self-reported and informant-reported memory complaints occur often in both clinical groups, which then necessitates the use of a comprehensive neuropsychological examination to make a differential diagnosis. However, the ability to identify cognitive symptoms that are predictive of aMCI through informant-based information may provide some clinical utility in accurately identifying individuals who are at risk for developing Alzheimer's disease (AD).

Methods

The current study utilized a case-control design using data from an ongoing validation study of the Alzheimer's Questionnaire (AQ), an informant-based dementia assessment. Data from 51 cognitively normal (CN) individuals participating in a brain donation program and 47 aMCI individuals seen in a neurology practice at the same institute were analyzed to determine which AQ items differentiated aMCI from CN individuals.

Results

Forward stepwise multiple logistic regression analysis which controlled for age and education showed that 4 AQ items were strong indicators of aMCI which included: repetition of statements and/or questions [OR 13.20 (3.02, 57.66)]; trouble knowing the day, date, month, year, and time [OR 17.97 (2.63, 122.77)]; difficulty managing finances [OR 11.60 (2.10, 63.99)]; and decreased sense of direction [OR 5.84 (1.09, 31.30)].

Conclusions

Overall, these data indicate that certain informant-reported cognitive symptoms may help clinicians differentiate individuals with aMCI from those with normal cognition. Items pertaining to repetition of statements, orientation, ability to manage finances, and visuospatial disorientation had high discriminatory power.

Objective

To assess the long-term effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) intake during gestation on visual development.

Study design

We examined the long-term effects in 136 school-age Inuit children exposed to high levels of n-3 PUFAs during gestation using visual evoked potentials (VEPs). VEP protocols using color and motion stimuli were used to assess parvo- and magnocellular responses. Concentrations of the two major n-3 PUFAs (DHA and EPA) were measured in umbilical cord and child plasma phospholipids, reflecting pre- and postnatal exposure, respectively.

Results

After adjustment for confounders, cord plasma DHA was associated with shorter latencies of the N1 and P1 components of the color VEPs. No effects were found for current n-3 PUFA body burden or motion-onset VEPs.

Conclusion

This study demonstrates beneficial effects of DHA intake during gestation on visual system function at school age. DHA is particularly important for the early development and long-term function of the visual parvocellular pathway.

OBJECTIVES

This study examined effects of iron deficiency anemia (IDA) on specific domains of infant cognitive function and the role of IDA-related socioemotional deficits in mediating and/or moderating these effects.

METHODS

Infants were recruited during routine 9-month visits to an inner-city clinic. IDA was defined as hemoglobin level <110 g/L with ≥2 abnormal iron deficiency indicators (mean corpuscular volume, red cell distribution width, zinc protoporphyrin, transferrin saturation, and ferritin). At 9 and 12 months, the Fagan Test of Infant Intelligence (FTII); A-not-B task; Emotionality, Activity, and Sociability Temperament Survey; and Behavior Rating Scale were administered. Analyses were adjusted for potential confounders, including age and sociodemographic variables.

RESULTS

Twenty-eight infants met criteria for IDA, 28 had nonanemic iron deficiency (NA ID) and 21 had iron sufficiency (IS). There was a linear effect for object permanence at 9 months: infants with IDA were least likely to exhibit object permanence, IS most likely, and NA ID intermediate. Infants with IDA and those with hemoglobin level ≤105 g/L showed poorer recognition memory on the FTII than infants without IDA. The Behavior Rating Scale orientation/engagement measure partially mediated these effects. Stronger effects of IDA on these outcomes were seen in infants who scored more poorly on the socioemotional measures.

CONCLUSIONS

These data indicate poorer object permanence and short-term memory encoding and/or retrieval in infants with IDA at 9 months. These cognitive effects were attributable, in part, to IDA-related deficits in socioemotional function. Children with poor socioemotional performance seem to be more vulnerable to the effects of IDA on cognitive function.

By contrast to the adult literature, in which a consistent parieto-frontal network for number processing has been identified, the data from studies of number processing in children have been less consistent, probably due to differences in study design and control conditions. Number processing was examined using functional MRI in 18 right-handed children (8–12 years) from the Cape Coloured community in Cape Town, South Africa using Proximity Judgment (PJ) and Exact Addition (EA) tasks. The findings were consistent with the hypothesis that, as in adults, the anterior horizontal intraparietal sulcus (HIPS) plays a major role in the representation and manipulation of quantity in children. The posterior medial frontal cortex, believed to be involved in performance monitoring in more complex arithmetic manipulations in adults, was extensively activated even for relatively simple symbolic number processing in the children. Other areas activated to a greater degree in the children included the left precentral sulcus, which may mediate number knowledge, and, for EA, the head of the caudate nucleus, which is part of a fronto-subcortical circuit involved in the behavioral execution of sequences. Two regions that have been linked to number processing in adults—the angular gyrus and posterior superior parietal lobule—were not activated in the children. The data are consistent with the inference that, although the functional specialization of the anterior HIPS may increase as symbolic number processing becomes increasingly automatic, this region and other elements of the parieto-frontal network identified in adults are already reliably and robustly activated by middle childhood.

Motor development, which allows infants to explore their environment, promoting cognitive, social, and perceptual development, can be influenced by cultural practices and nutritional factors, such as iron deficiency. This study compared fine and gross motor development in 209 9-month-old infants from urban areas of China, Ghana, and USA (African-Americans) and considered effects of iron status. Iron deficiency anemia was most common in the Ghana sample (55%) followed by USA and China samples. Controlling for iron status, Ghanaian infants displayed precocity in gross motor development and most fine-motor reach-and-grasp tasks. US African-Americans performed the poorest in all tasks except bimanual coordination and the large ball. Controlling for cultural site, iron status showed linear trends for gross motor milestones and fine motor skills with small objects. Our findings add to the sparse literature on infant fine motor development across cultures. The results also indicate the need to consider nutritional factors when examining cultural differences in infant development.

Objective

To describe a case of early-onset Alzheimer's disease (AD) in an apolipoprotein (Apo) ∊2/∊2 homozygote.

Background

Apo ∊2/∊2 is the rarest of the ApoE genotypes, representing only 1.4% of the population. Cognitive decline in ApoE ∊2 homozygotes has rarely been reported. Case Report/Methods: We report a 58-year-old Apo ∊2/∊2 female who meets clinical criteria for probable AD as confirmed by neuropsychological testing, positron emission/computed tomography scan, CSF analysis and genetic screening for known mutations.

Results

The clinical course is typical of AD, with progressive cognitive and functional decline.

Conclusion

Clinically confirmed early-onset AD is atypical in ApoE2 homozygotes but can occur.

Infant symbolic play was examined in relation to prenatal alcohol exposure and socioenvironmental background and to predict which infants met criteria for fetal alcohol syndrome (FAS) at 5 years. 107 Cape Coloured, South African infants born to heavy drinking mothers and abstainers/light drinkers were recruited prenatally. Complexity of play, socio-demographic and psychological correlates of maternal alcohol use, and quality of parenting were assessed at 13 months, and IQ and FAS diagnosis at 5 years. The effect of drinking on spontaneous play was not significant after control for social environment. By contrast, prenatal alcohol and quality of parenting related independently to elicited play. Elicited play predicted 5-year Digit Span and was poorer in infants subsequently diagnosed with FAS/partial FAS and in nonsyndromal heavily exposed infants, compared with abstainers/light drinkers. Thus, symbolic play may provide an early indicator of risk for alcohol-related deficits. The independent effects of prenatal alcohol and quality of parenting suggest that infants whose symbolic play is adversely affected by alcohol exposure may benefit from stimulation from a responsive caregiver.

The aim of this pilot study is to determine the feasibility and clinical utility of a brief, informant-based screening questionnaire for Alzheimer’s disease (AD) that can be administered in a primary care setting. The Alzheimer’s Questionnaire (AQ) was administered to the informants of 188 patients in 3 dementia clinics (50 cognitively normal, 69 mild cognitive impairment (MCI), 69 AD). Total score for the AQ is based upon the sum of clinical symptom items in which the informant responds as being present. Clinical symptoms which are known to be highly predictive of the clinical AD diagnosis are given greater weight in the total AQ score. The mean time of administration of the AQ was 2.6 ± 0.6 minutes. Sensitivity and specificity were found to be high for detecting both AD (98.55, 96.00) and MCI (86.96, 94.00) with ROC curves yielding AUC values of 0.99 and 0.95, respectively. This pilot study indicates that the AQ is a brief, sensitive measure for detecting both MCI and AD and could be easily implemented in a primary care setting.

Many previous attempts by fetal alcohol spectrum disorders researchers to compare data across multiple prospective and retrospective human studies have failed due to both structural differences in the collected data as well as difficulty in coming to agreement on the precise meaning of the terminology used to describe the collected data. Although some groups of researchers have an established track record of successfully integrating data, attempts to integrate data more broadly amongst different groups of researchers have generally faltered. Lack of tools to help researchers share and integrate data has also hampered data analysis. This situation has delayed improving diagnosis, intervention, and treatment before and after birth. We worked with various researchers and research programs in the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CI-FASD) to develop a set of common data dictionaries to describe the data to be collected, including definitions of terms and specification of allowable values. The resulting data dictionaries were the basis for creating a central data repository (CI-FASD Central Repository) and software tools to input and query data. Data entry restrictions ensure that only data which conform to the data dictionaries reach the CI-FASD Central Repository. The result is an effective system for centralized and unified management of the data collected and analyzed by the initiative, including a secure, long-term data repository. CI-FASD researchers are able to integrate and analyze data of different types, collected using multiple methods, and collected from multiple populations, and data are retained for future reuse in a secure, robust repository.

Given the level of interest and activity in the race to find a treatment for Alzheimer's disease, it is expected that a reasonably safe and effective drug will be identified within the next decade. It may be worthwhile to pause periodically during the course of this race to take stock of what we have learned. Over the past few years, a number of trials have been conducted with promising new compounds (including some with novel mechanisms of action) that failed to meet primary endpoints and so were discontinued from clinical development. This article reviews a set of molecules with a range of mechanisms that have been trialed but with negative results. This article also examines the reasons for the negative findings and summarizes some of what we have learned from these experiences.

Objective

This study was conducted to compare quality of mother-infant interactions during feeding in infants with or without iron deficiency anemia (IDA).

Method

Infants and caregivers were screened at their 9- to 10-month-old health maintenance visits at an inner-city clinic in Detroit. Those who were full-term and healthy received a venipuncture blood sample to assess iron status. Of the 77 infants who met final iron status criteria, 68 infants and mothers were videotaped during feeding interaction at the Child Development Research Laboratory. The quality of mother-infant interaction during feeding was scored on the Nursing Child Assessment Feeding Scale (NCAFS). Twenty-five infants with IDA (HB < 110 g/L and at least 2 abnormal iron measures) were compared to 43 non-anemic infants (HB ≥ 110 g/L) using ANOVA and GLM models with covariate control.

Results

Mothers of IDA infants responded with significantly less sensitivity to infant cues and less cognitive and social-emotional growth fostering behavior than mothers of non-anemic infants. The pattern of results was similar for scales of contingent behaviors. The magnitude of the differences in maternal ratings was large (0.8-1.0 SD after covariate adjustment). IDA infants were rated significantly lower on clarity of cues and overall (effect sizes 0.5 SD).

Conclusion

IDA in infancy was associated with less optimal mother-infant interactions during feeding. Future interventions might target feeding interaction and consider effects on infant iron status and developmental/behavioral outcomes among IDA infants, as well as infant feeding practices per se.

Background

Iron deficiency (ID) during early development impairs myelination and basal ganglia function in animal models.

Aims

To examine the effects of iron deficiency anemia (IDA) and iron deficiency (ID) without anemia on infant motor skills that are likely related to myelination and basal ganglia function.

Study design

Observational study.

Subjects

Full-term inner-city African-American 9- to 10-month-old infants who were free of acute or chronic health problems with iron status indicators ranging from IDA to iron sufficiency (n = 106). Criteria for final iron status classification were met by 77 of these infants: 28 IDA, 28 non-anemic iron-deficient (NA ID), and 21 iron-sufficient (IS).

Outcome measures

Gross motor developmental milestones, Peabody Developmental Motor Scale, Infant Neurological International Battery (INFANIB), motor quality factor of the Bayley Behavioral Rating Scale, and a sequential/bi-manual coordination toy retrieval task. General linear model analyses tested for linear effects of iron status group and thresholds for effects.

Results

There were linear effects of iron status on developmental milestones, Peabody gross motor (suggestive trend), INFANIB standing item, motor quality, and toy retrieval. The threshold for effects was ID with or without anemia for developmental milestones, INFANIB standing item, and motor quality and IDA for toy retrieval.

Conclusions

Using a comprehensive and sensitive assessment of motor development, this study found poorer motor function in ID infants with and without anemia. Poorer motor function among non-anemic ID infants is particularly concerning, since ID without anemia is not detected by common screening procedures and is more widespread than IDA.

Objective

To determine if longer breastfeeding is associated with higher infant lead concentrations.

Study design

Data were analyzed from 3 studies of developmental effects of iron deficiency in infancy: Costa Rica (1981–1984), Chile (1991–1996), and Detroit (2002–2003). Pearson product-moment or partial correlation coefficients assessed the relation between duration of breastfeeding and lead levels.

Results

Over 93% of Costa Rica and Chile samples was breastfed, n = 179 and 323 breastfed infants, respectively (mean weaning age, 8–10 months), as was 35.6% of the Detroit sample, n = 53 breastfed infants (mean weaning age, 4.5 months). Lead concentrations averaged 10.8 μg/dL (Costa Rica, 12–23 months), 7.8 μg/dL (Chile, 12 months), and 2.5 μg/dL (Detroit, 9–10 months). Duration of breastfeeding as sole milk source and total breastfeeding correlated with lead concentration in all samples (r values = .14 to .57, p values = .06 to <.0001).

Conclusions

Longer breastfeeding was associated with higher infant lead concentration in 3 countries, in 3 different decades, in settings differing in breastfeeding patterns, environmental lead sources, and infant lead levels. The results suggest that monitoring lead concentrations in breastfed infants be considered.

This study assessed 9 kinematic characteristics of infants’ reach and grasp to test the hypothesis that iron deficiency anemia (IDA) delays upper extremity motor development. Reach and grasp movements, recorded with a 3D-motion capture system, were compared in 9- to 10-month-old infants (4 IDA vs. 5 iron-sufficient [IS]). Based on normative motor development data available for 6 characteristics, the results indicated poorer upper extremity control in IDA infants: 2 characteristics showed statistically significant group differences despite small n, and the other 4 had strong indications for such results (effect sizes [Cohen's d] > 1.2). The remaining 3 measures, for which normative studies do not show developmental changes in this age period, showed significant or moderate-to- large effect differences. Poorer upper-extremity control in IDA infants in the short-term in this study and in the long-term despite iron therapy in other studies suggests that a motor intervention may be warranted when IDA is detected in infancy.