Effect of Peanut Paste-based Ready-to-use School Meals With and Without Milk on Fluid Cognition in Northern Ghana: A Randomized Controlled Trial.

BACKGROUND: Few studies have investigated the role of school feeding in low- and middle-income countries as a means of improving childhood cognition. Peanut/milk ready-to-use food (PM-RUF) or cowpea offers an affordable, scalable option that might improve cognition. OBJECTIVES: To determine whether micronutrient-fortified PM-RUF or peanut/cowpea ready-to-use food (PC-RUF) would improve fluid cognition as assessed by 4 tests from the National Institutes of Health Toolbox Cognitive Battery when compared with a micronutrient-fortified millet porridge (FP) after a year of school feeding. METHODS: An individually randomly assigned, investigator-blinded, controlled clinical trial was conducted at 6 schools in Mion District in rural northern Ghana. Eight hundred seventy-one school children aged 5-12 y were randomly assigned and allocated to receive PM-RUF (n = 282), PC-RUF (n = 292), or FP (n = 297), each providing ∼400 kcal/d. The primary outcomes were 4 fluid cognition test scores: Dimensional Change Card Sort test, Flanker Inhibitory Control and Attention test, Pattern Comparison Processing Speed test, and a modified List Sorting Working Memory test. Secondary outcomes included a composite median ranking of the 4 primary outcomes and anthropometry changes. RESULTS: Among the 871 participants (median age, 8.8 y; 47% female), 795 (91%) completed endline cognitive testing. Median attendance rates exceeded 87% in all groups. PM-RUF group demonstrated better fluid cognition on the Dimensional Change Card Sort test [odds ratio (OR): 1.5; 95% CI: 1.1, 2.0; P = 0.016] and Pattern Comparison Processing Speed test (OR: 1.4; 95% CI: 1.0, 1.9; P = 0.026) than FP, whereas there were no significant differences on Flanker Inhibitory Control and Attention or List Sorting Working Memory tests. PC-RUF group demonstrated no improvement over FP on any cognitive tests. PM-RUF group had superior fluid cognition composite median rankings (OR: 1.5; 95% CI: 1.1, 2.0; P = 0.007). CONCLUSIONS: Among rural Ghanaian children aged 5-12 y, PM-RUF compared with FP resulted in superior fluid cognition. This trial was registered at clinicaltrials.gov as NCT04349007.

Enhancement of taste by retronasal odors in patients with Wolfram syndrome and decreased olfactory function.

Wolfram syndrome is a rare disease characterized by diabetes, neurodegeneration, loss of vision, and audition. We recently found, in a young sample of participants (mean age 15 years), that Wolfram syndrome was associated with impairment in smell identification with normal smell sensitivity and whole-mouth taste function. However, these senses were assessed separately, and it is unknown whether smell-taste interactions are altered in Wolfram syndrome, which was the focus of this study. Participants with Wolfram syndrome (n = 36; 18.2 ± 6.8 years) and sex-age-equivalent healthy controls (n = 34) were assessed with a battery of sensory tests. Using sip-and-spit methods, participants tasted solutions containing gustatory and olfactory stimuli (sucrose with strawberry extract, citric acid with lemon extract, sodium chloride in vegetable broth, and coffee) with and without nose clips, and rated perceived taste and retronasal smell intensities using the generalized Labeled Magnitude Scale. Participants also completed n-butanol detection thresholds and the University of Pennsylvania Smell Identification Test (UPSIT). Retronasal smell increased taste intensity of sucrose, sodium chloride, and coffee solutions similarly in both groups (P values <0.03). Compared with the control group, participants in the Wolfram group had lower UPSIT scores and reduced smell sensitivity, retronasal intensity, and saltiness (P values <0.03), but rated other taste intensities similarly when wearing the nose clip. Despite impairments in orthonasal smell identification, odor-induced taste enhancement was preserved in participants with Wolfram syndrome who still had some peripheral olfactory function. This finding suggests that odor-induced taste enhancement may be preserved in the presence of reduced olfactory intensity.

The Weekly Calendar Planning Activity to Assess Functional Cognition in Parkinson Disease.

The Weekly Calendar Planning Activity (WCPA) may improve understanding of functional cognition in people with Parkinson disease (PwPD) without dementia. We aimed to determine if WCPA performance (a) discriminates between PwPD with and without cognitive impairment and healthy controls and (b) correlates with other indicators of cognition and daily function. This was a cross-sectional study. Parkinson disease (PD) participants without dementia were divided into normal cognition (PD-NC, n = 25) and possible mild cognitive impairment (PD-MCI, n = 21) groups. Their WCPA performance was compared with that of a normative sample (n = 196) and correlated with neuropsychological test performance and self-reported cognition and participation. Both the PD-MCI and PD-NC groups had impaired WCPA performance. WCPA performance correlated with executive function, processing speed, and self-reported cognition and participation. The WCPA can detect functional cognitive deficits in PwPD without dementia and can inform occupational therapy interventions to support functional cognition, occupational performance, and participation in this population.

Psychiatric Diagnoses and Medications in Wolfram Syndrome.

Background: Wolfram Syndrome is a rare genetic disorder usually resulting from pathogenic variation in the WFS1 gene, which leads to an exaggerated endoplasmic reticulum (ER) stress response. The disorder is typically characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy, hearing loss, and neurodegenerative features. Existing literature suggests it may also have psychiatric manifestations. Objective: To examine lifetime psychiatric diagnoses and medication history in Wolfram Syndrome. Method: Child, adolescent, and young adult Wolfram Syndrome participants (n=39) were assessed by a child & adolescent psychiatrist to determine best estimate DSM-5 lifetime psychiatric diagnoses as well as psychoactive medication history. In addition, the Child & Adolescent Symptom Inventory-5 (CASI-5) Parent Checklist was used to determine likely psychiatric diagnoses based on symptom counts in Wolfram Syndrome patients (n=33), type 1 diabetes (n=15), and healthy comparison (n=18) groups. Results: Study participants with Wolfram Syndrome had high lifetime rates of anxiety disorders (77%). Also, 31% had an obsessive-compulsive spectrum disorder, 33% had a mood disorder, 31% had a neurodevelopmental or disruptive behavior disorder, and 31% had a sleep-wake disorder. More than half of Wolfram Syndrome participants had taken at least one psychoactive medication, and one third had taken at least one selective serotonin reuptake inhibitor (SSRI). Some individuals reported poor response to sertraline but better response after switching to another SSRI (fluoxetine or citalopram). In general, people with Wolfram Syndrome often reported benefit from psychotherapy and/or commonly used psychoactive medications appropriate for their psychiatric diagnoses. Conclusions: Wolfram Syndrome may be associated with elevated risk for anxiety and obsessive-compulsive spectrum disorders, which seem generally responsive to usual treatments for these disorders.

Cognitive Correlates of Instrumental Activities of Daily Living Performance in Parkinson Disease Without Dementia.

OBJECTIVE: To investigate cognitive correlates of instrumental activities of daily living (IADL) performance among people with Parkinson disease (PD) without dementia. DESIGN: Cross-sectional. SETTING: Academic medical center. PARTICIPANTS: Volunteer sample (N=161) comprising participants with PD without dementia (n=102) and healthy comparison (HC) participants (n=59). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Performance-based assessment of cognitively-demanding IADL (meal preparation, bill paying, shopping, medication management, small home repair), neuropsychological tests (attentional control/flexibility, planning, working memory, memory, crystallized intelligence), and measures of motor function and other characteristics (eg, depressive symptoms). RESULTS: There were no group differences in neuropsychological test performance (P>.06). The PD group performed more poorly than the HC group on a number of cognitive IADL tasks (P<.04). After accounting for the effects of motor impairment and other disease-related characteristics, neuropsychological test performance accounted for a small but unique portion of the variance in performance of all cognitive IADL combined, meal preparation, shopping, and medication management in the PD group (R 2=4%-13%; P≤.01). CONCLUSIONS: The PD group had cognitive IADL performance limitations despite being unimpaired on neuropsychological tests. Within PD, neuropsychological test performance accounted for a small but significant portion of the variance in cognitive IADL performance over and above the effects of motor and other impairments. These results support the added value of using performance-based IADL assessments in functional evaluations of individuals with early and mild PD without dementia.

Taste and smell function in Wolfram syndrome.

BACKGROUND: Wolfram syndrome is a rare genetic disease characterized by insulin-dependent diabetes, optic nerve atrophy, sensorineural hearing loss and neurodegeneration. Although olfactory dysfunction, a classical clinical marker of neurodegenerative processes, has been reported in Wolfram syndrome, its use as a clinical marker in Wolfram is limited due to data scarcity. In addition, it is unknown whether Wolfram syndrome affects the sense of taste. METHODS: Smell and taste perception were assessed in participants with Wolfram syndrome (n = 40) who were 15.1 ± 6.0 years of age (range: 5.1-28.7 years) and two sex- and age-matched control groups: one group with type 1 diabetes mellitus (T1D; n = 25) and a healthy control group (HC; n = 29). Smell sensitivity was assessed by measuring n-butanol detection thresholds and smell identification by using the University of Pennsylvania Smell Identification Test (UPSIT). Taste function was assessed using NIH Toolbox, which includes the assessment of sucrose (sweet) taste preference, and perceived intensity of sucrose, sodium chloride (salty), and quinine hydrochloride (bitter) both in the tip of the tongue (regional test) and the whole mouth. RESULTS: Smell sensitivity was not significantly different among groups; however, smell identification was impaired in Wolfram syndrome, as reflected by significantly lower UPSIT scores in Wolfram syndrome compared to HC and T1D (P < 0.001). Compared to participants in the control groups, participants with Wolfram syndrome had a blunted perception of sweetness and saltiness when taste stimuli were applied regionally (P < 0.05), but differences in perceived intensity were no longer significant among groups when taste stimuli were tasted with the whole mouth. Groups preferred similar sucrose concentrations. CONCLUSION: Wolfram syndrome was associated with olfactory dysfunction. However, the olfactory dysfunction was qualitative (related to smell identification) and not secondary to olfactory insensitivity or diabetes, suggesting is arising from dysfunction in central olfactory brain regions. In contrast to olfaction, and despite decreased perception of taste intensity in the anterior tongue, the sense of taste was overall well-conserved in individuals with Wolfram syndrome. Future longitudinal studies of taste and smell perception in Wolfram syndrome will be important to determine the use of the chemical senses as clinical markers of disease progression.

Understanding activity participation among individuals with Wolfram Syndrome.

INTRODUCTION: Wolfram Syndrome (WFS) is a rare genetic disease associated with a variety of progressive metabolic and neurologic impairments. Previous research has focused on WFS-related impairments and biomarkers for disease progression; however, information about how WFS impacts participation in daily activities is lacking. METHODS: WFS (n=45; 20 children, 25 adults) participants completed an online questionnaire about activity participation. Thirty-six non-WFS comparison participants (11 children; 25 adults) completed a portion of the questionnaire. Symptom data from a subset of WFS participants (n=20) were also examined in relation to participation data. RESULTS: WFS children and adults had lower participation than non-WFS children and adults in almost all activity domains, and social and exercise-related activities were the most problematic. In the subset of WFS adults with symptom data, poorer vision, balance, gait, hearing, and overall symptom severity related to lower participation. CONCLUSIONS: WFS appears to negatively impact participation in a variety of activities, and this effect may increase as people age and/or WFS progresses. The most functionally-pertinent WFS symptoms are those associated with neurodegeneration especially vision loss and walking and balance problems. This study revealed symptoms and activity domains that are most relevant for people with WFS and, thus, can inform current practice and treatment development research.

Self-management program participation and social support in Parkinson's disease: Mixed methods evaluation.

Aims: To explore the potential influence of the Stanford Chronic Disease Self-Management Program (CDSMP) on social support in Parkinson disease (PD). Methods: This was a quasi-experimental mixed methods design. Volunteers with PD (n=27) and care partners (n=6) completed the CDSMP, questionnaires of social support and self-management outcomes, and an interview about social support in relation to CDSMP participation. PD participants (n=19) who did not participate in the CDSMP completed the questionnaires for quantitative comparison purposes. Results: Regarding the quantitative data, there were no significant effects of CDSMP participation on social support questionnaire scores; however, there were some positive correlations between changes in social support and changes in self-management outcomes from pre- to post-CDSMP participation. Three qualitative themes emerged from the interviews: lack of perceived change in amount and quality of social support, positive impact on existing social networks, and benefit from participating in a supportive PD community. Conclusions: Although participants did not acknowledge major changes in social support, there were some social support-related benefits of CDSMP participation for PD participants and care partners. These findings provide a starting point for more in-depth studies of social support and self-management in this population.

The effects of disease-related symptoms on daily function in Wolfram Syndrome.

OBJECTIVE: To investigate daily function among individuals with Wolfram Syndrome (WFS) and examine whether any limitations are related to disease-related symptoms. METHODS: WFS (n = 31), Type 1 diabetic (T1DM; n = 25), and healthy control (HC; n = 29) participants completed the Pediatric Quality of Life Questionnaire (PEDSQL) Self and Parent Report. PEDSQL domain scores were compared among these groups and between WFS patients with and without specific disease-related symptoms. Relationships between PEDSQL scores and symptom severity as assessed by the Wolfram Unified Rating Scale (WURS) Physical Scale were also examined. RESULTS: Across most domains, the WFS group had lower PEDSQL Self and Parent Report scores than the T1DM and HC groups. WFS participants with urinary, sleep, and temperature regulation problems had lower PEDSQL scores than those without. The WURS Physical Scale correlated with Self and Parent Report PEDSQL domains. WFS group Self and Parent Reports correlated with each other. CONCLUSIONS: The WFS group reported lower daily function compared to T1DM and HC groups. Within WFS, worse symptom severity and the specific symptoms of sleep, temperature regulation, and urinary problems were associated with poorer daily function. These findings provide rationale for an increased emphasis on identifying, treating and understanding these less well-known symptoms of WFS.

A longitudinal investigation of cognitive function in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: Cross-sectional studies find altered cognition in youth with type 1 diabetes mellitus (T1DM). However, few longitudinal studies have examined the trajectories of their cognitive performance over time. The aims of this study were to explore longitudinal change in cognitive function in youth with T1DM as compared with nondiabetic sibling controls, and how glycemic control and age of onset influence cognitive performance over time. METHODS: We assessed crystallized intelligence, visual-spatial ability, delayed memory, and processing speed at 3 time points using the same cognitive tasks in youth with T1DM and sibling controls. Hierarchical linear modeling examined relationships between diabetes, hyperglycemia (HbA1c values), age of onset, and cognition over 5.5 y. RESULTS: Youth with diabetes performed worse than controls on visual-spatial ability and memory tasks over time, and did not improve as much in processing speed. Greater hyperglycemia was associated with lower crystallized intelligence and slower processing speed but better memory across all time points. There was a stronger negative relationship between hyperglycemia and visual-spatial ability for youth with earlier compared with later onset diabetes. Importantly, within-person decreases in hyperglycemia between time points were associated with improved visual-spatial ability and faster processing speed. CONCLUSIONS: On average, differences in cognitive function between youth with T1DM and nondiabetic relatives are maintained or increase during childhood and adolescence. Hyperglycemia and age of onset can have negative effects on the developmental trajectories of cognitive processes in youth with T1DM. However, treatments that lower hyperglycemia may lead to improved cognitive function in youth with T1DM.

Prenatal DHA supplementation and infant attention.

BACKGROUND: Results of randomized trials on the effects of prenatal docosahexaenoic acid (DHA) on infant cognition are mixed, but most trials have used global standardized outcomes, which may not be sensitive to effects of DHA on specific cognitive domains. METHODS: Women were randomized to 600 mg/d DHA or a placebo for the last two trimesters of pregnancy. Infants of these mothers were then followed on tests of visual habituation at 4, 6, and 9 mo of age. RESULTS: DHA supplementation did not affect look duration or habituation parameters but infants of supplemented mothers maintained high levels of sustained attention (SA) across the first year; SA declined for the placebo group. The supplemented group also showed significantly reduced attrition on habituation tasks, especially at 6 and 9 mo. CONCLUSION: The findings support with the suggestion that prenatal DHA may positively affect infants' attention and regulation of state.

Clinical presentation and memory function in youth with type 1 diabetes.

OBJECTIVE: While cerebral edema and diabetic ketoacidosis (DKA) in type 1 diabetes (T1DM) have well-described acute effects on cognition, little is known about the impact of clinical presentation on longer term cognitive outcomes. We hypothesized that clinical factors (degree of hyperglycemia exposure and DKA) at the time of diagnosis would relate to cognition within 3.5 months later in children with T1DM. METHODS: Cognitive testing was performed on children 7-17 years old with T1DM (n = 66) within 3.5 months of diagnosis and siblings without T1DM (n = 33). Overall intelligence, processing speed, and memory (including a sensitive long-delay spatial memory test; spatial delayed response or SDR) were assessed. Medical records were reviewed for hemoglobin A1c (HbA1c), DKA status, and other clinical factors at diagnosis. RESULTS: Within the group with T1DM, 17 children presented in DKA and 49 did not. After adjusting for age, gender, and socioeconomic status, the subgroup with T1DM and DKA at diagnosis performed worse on the long-delay SDR task compared to sibling controls (p = 0.006). In addition, within the group with T1DM, higher HbA1c at diagnosis was associated with worse performance on the long-delay SDR task (p = 0.027). Performance on the other cognitive tasks was not different across groups or subgroups. CONCLUSIONS: DKA and degree of hyperglycemia exposure at diagnosis have implications for long-delay spatial memory function within 3.5 months of diagnosis. These findings suggest that early detection of T1DM, which decreases risk for prolonged exposure to hyperglycemia and DKA, may avoid negative effects on memory function.

Selective cognitive and psychiatric manifestations in Wolfram Syndrome.

BACKGROUND: Wolfram Syndrome (WFS) is known to involve diabetes mellitus, diabetes insipidus, optic nerve atrophy, vision loss, hearing impairment, motor abnormalities, and neurodegeneration, but has been less clearly linked to cognitive, sleep, and psychiatric abnormalities. We sought to determine whether these abnormalities are present in children, adolescents, and young adults with WFS compared to age- and gender-matched individuals with and without type 1 diabetes using standardized measures. METHODS: Individuals with genetically-confirmed WFS (n = 19, ages 7-27) were compared to age- and gender- equivalent groups of individuals with type 1 diabetes (T1DM; n = 25), and non-diabetic healthy controls (HC: n = 25). Cognitive performance across multiple domains (verbal intelligence, spatial reasoning, memory, attention, smell identification) was assessed using standardized tests. Standardized self- and parent-report questionnaires on psychiatric symptoms and sleep disturbances were acquired from all groups and an unstructured psychiatric interview was performed within only the WFS group. RESULTS: The three groups were similar demographically (age, gender, ethnicity, parental IQ). WFS and T1DM had similar duration of diabetes but T1DM had higher HbA1C levels than WFS and as expected both groups had higher levels than HC. The WFS group was impaired on smell identification and reported sleep quality, but was not impaired in any other cognitive or self-reported psychiatric domain. In fact, the WFS group performed better than the other two groups on selected memory and attention tasks. However, based upon a clinical evaluation of only WFS patients, we found that psychiatric and behavioral problems were present and consisted primarily of anxiety and hypersomnolence. CONCLUSIONS: This study found that cognitive performance and psychological health were relatively preserved WFS patients, while smell and sleep abnormalities manifested in many of the WFS patients. These findings contradict past case and retrospective reports indicating significant cognitive and psychiatric impairment in WFS. While many of these patients were diagnosed with anxiety and hypersomnolence, self-reported measures of psychiatric symptoms indicated that the symptoms were not of grave concern to the patients. It may be that cognitive and psychiatric issues become more prominent later in life and/or in later stages of the disease, but this requires standardized assessment and larger samples to determine. In the relatively early stages of WFS, smell and sleep-related symptoms may be useful biomarkers of disease and should be monitored longitudinally to determine if they are good markers of progression as well. TRIAL REGISTRATION: Current Clinicaltrials.gov Trial NCT02455414 .

Long-chain polyunsaturated fatty acid supplementation in infancy reduces heart rate and positively affects distribution of attention.

A double-blind, randomized, controlled, parallel-group prospective trial was conducted to determine whether a dose-response existed for four different levels of docosahexaenoic acid (DHA) supplementation on the cognitive performance of infants. A total of 122 term infants were fed one of four different formulas varying in their DHA composition (0.00, 0.32, 0.64, and 0.96% of total fatty acids as DHA) from birth to 12 mo. The three DHA-supplemented formulas also contained 0.64% of total fatty acids as arachidonic acid (ARA, 20:4n-6). Infants were tested at 4, 6, and 9 mo of age on a visual habituation protocol that yielded both behavioral and psychophysiological indices of attention. Infants in all DHA+ARA-supplemented conditions had lower heart rates than those in the unsupplemented condition; there was no dose-response for this effect. The distribution of time that infants spent in different phases of attention (a cognitive index derived from the convergence of behavioral and cardiac responses) varied as a function of dosage. Infants supplemented at the two lower DHA doses spent proportionately more time engaged in active stimulus processing than infants fed the unsupplemented formula, whereas infants fed the highest dose were intermediate and did not differ from any other group.