Cognitive Outcomes and Relationships with Phenylalanine in Phenylketonuria: A Comparison between Italian and English Adult Samples
Abstract
:1. Introduction
2. Method
2.1. Participants
2.2. Ethical Approval
2.3. Metabolic Measures
2.4. Cognitive Assessment
2.4.1. Visual Attention
2.4.2. Visuo-Motor Coordination
2.4.3. Complex Executive Functions
2.4.4. Short-term Memory/Working Memory
2.4.5. Sustained Attention
2.4.6. Verbal Memory and Learning
2.4.7. Visual Memory and Learning
3. Data Analyses
4. Results
4.1. Demographics
4.2. Cognitive Performance
4.2.1. AwPKU vs. Controls
4.2.2. Italian AwPKU vs. English AwPKU
4.3. Cognitive Outcomes in Relation to Metabolic Control
5. Discussion
5.1. Metabolic Control
5.2. Cognitive Impairments
- -
- -
- Executive functions in terms of flexibility and planning (TMT B and B–A and verbal fluency), but no impairment in the WCST (see also Moyle et al. [49] for impairments in fluency, but no impairments in the TMT B; see also Brumm et al. [25]; Smith et al. [50], for impairments in the WCST; see Ris et al. [51], and Channon et al. [52], for impairments in a test similar to the WCST).
- -
- -
6. Conclusions
Limitations
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Italian AwPKU | English AwPKU | English vs. Italian | |||
---|---|---|---|---|---|
N = 19 | N = 19 | p Value | |||
Mean | SD | Mean | SD | ||
Age | 25.4 (range: 19–33) | 4.1 | 25.3 (range: 18–36) | 6.1 | n.s. |
Education (in years) | 14 | 1.8 | 14.6 | 1.9 | n.s. |
Gender (M/F) | 8//11 | 8//11 | |||
Verbal IQ | 98.8 | 12.9 | 100.4 | 8.9 | n.s. |
Performance IQ | 99.3 | 15 | 103.3 | 12.9 | n.s. |
Full IQ | 98.9 | 14.5 | 102.1 | 10.4 | n.s. |
Childhood (0–10 years) | |||||
Phe Average Median | 499 | 149 | 386 | 168 | p = 0.04 |
Phe Fluctuation | 227 | 63 | 198 | 50 | n.s. |
Mean N observationsper participant | 208 | 79 | 259 | 156 | n.s. |
Adolescence (11–16 years) | |||||
Phe Average Median | 702 | 194 | 612 | 293 | n.s. |
Phe Fluctuation | 170 | 51 | 165 | 34 | n.s. |
Mean N obs. per participant | 77 | 54 | 98 | 74 | n.s. |
Adulthood (17 years +) | |||||
Phe Average Median | 970 | 239 | 733 | 344 | p = 0.02 |
Phe Variation | 217 | 65 | 122 | 41 | p < 0.001 |
Mean N obs. per participant | 58 | 49 | 62 | 58 | n.s. |
Lifetime | |||||
Phe Average Median | 695 | 198 | 516 | 233 | p = 0.02 |
Phe Fluctuation (SD) | 208 | 46 | 171 | 33 | p < 0.01 |
Mean N observations. per participant | 344 | 149 | 419 | 232 | n.s. |
Current Phe | 1042 | 428 | 677 | 382 | p = 0.01 |
Range | 454–2081 | 65–1465 |
ITALIAN PARTICIPANTS (N = 19 In Each Group) | ENGLISH PARTICIPANTS (N = 19 In Each Group) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
AwPKU | Controls | Diff. | AwPKU | Controls | Diff. | |||||
Mean | SD | Mean | SD | p Value | Mean | SD | Mean | SD | p Value | |
Age | 25.4 | 4.1 | 24.7 | 3.4 | n.s. | 25.3 | 6.1 | 24.4 | 5.35 | n.s. |
Education (in years) | 14.0 | 1.8 | 13.9 | 1.7 | n.s. | 14.6 | 1.9 | 14.8 | 1.7 | n.s. |
Gender (M/F) | 8//11 | 8//11 | 7//12 | 6//13 | ||||||
VIQ | 98.8 | 13 | 108.5 | 13.1 | 0.03 | 100.4 | 8.9 | 109.6 | 9.6 | <0.001 # |
PIQ | 99.3 | 15 | 107.1 | 9.6 | 0.07 | 103.3 | 12.9 | 110.2 | 12.6 | n.s. |
FIQ | 98.9 | 15 | 110.1 | 12.0 | 0.01 | 102.1 | 10.4 | 111.1 | 10.3 | 0.01 |
VISUAL ATTENTION | ||||||||||
Simple Detection (RT—ms) | 325 | 46 | 315 | 44.6 | n.s. | 331 | 50.7 | 304.9 | 51.2 | 0.06 |
Detention with Distractors | ||||||||||
RT—ms | 483 | 104 | 430 | 58 | 0.02 | 433 | 56.4 | 392 | 54.2 | 0.03 |
% errors | 0.8 | 0.6 | 0.5 | 1.1 | n.s. | 0.8 | 0.8 | 0.5 | 0.6 | n.s. |
Feature Search | ||||||||||
RT—ms | 752 | 262 | 586 | 113 | 0.02 | 581 | 111 | 492.3 | 70.5 | 0.01 |
% errors | 1.6 | 4.7 | 0.6 | 1.2 | n.s. | 1.9 | 2.6 | 2.3 | 2.3 | n.s. |
Conjunction Search | ||||||||||
RT—ms | 1152 | 237 | 938 | 203 | <0.001 # | 998 | 162 | 846 | 129.0 | <0.001 # |
% errors | 3.2 | 4.7 | 2.8 | 4.7 | n.s. | 2 | 2.2 | 3.5 | 5.4 | n.s. |
VISUO-MOTOR COORDINATION | ||||||||||
Pegboard (Time–s) | 76.7 | 11 | 70.6 | 9.0 | 0.06 | 71.9 | 9.9 | 66.0 | 6.1 | 0.03 |
Digit Symbol (%errors in 90 s) | 41.6 | 12 | 39.4 | 9.1 | <0.001 # | 37.1 | 11.6 | 27.9 | 10.3 | 0.01 |
Trail-Making Test A (Time–s) | 32.4 | 15 | 29.9 | 12.1 | n.s. | 24.0 | 7.0 | 20.2 | 3.7 | 0.04 |
EXECUTIVE FUNCTIONS | ||||||||||
WCST | ||||||||||
Total errors | 13.6 | 6.9 | 13.6 | 5.3 | n.s. | 13.8 | 8.6 | 11.9 | 5.5 | n.s. |
Perseverative responses | 7.0 | 3.1 | 7.8 | 3.3 | n.s. | 7.9 | 5.1 | 7.5 | 5.3 | n.s. |
N of Completed Categories | 4.0 | 1.1 | 4.1 | 1.0 | n.s. | 3.9 | 1.2 | 4.3 | 0.9 | n.s. |
Trail-Making Test | ||||||||||
B (sec) | 79.8 | 34 | 54.4 | 19.7 | 0.01 | 42 | 10.8 | 43.2 | 16.0 | n.s. |
B–A (sec) | 47.5 | 29 | 24.4 | 13.1 | <0.001 # | 18 | 8.0 | 22.9 | 14.3 | n.s. |
Verbal Fluency | ||||||||||
Letter (correct answers) | 39.0 | 11 | 47.5 | 9.3 | 0.01 | 36.3 | 11.6 | 40.5 | 15.0 | n.s. |
Semantic (correct answers) | 20.1 | 4.8 | 23.5 | 3.6 | 0.02 | 21.6 | 5.8 | 25.1 | 5.0 | 0.06 |
Rey Auditory Verbal Learning | ||||||||||
Retention after interference (% errors A6) | 17.2 | 13 | 8.4 | 7.6 | 0.02 | 19.6 | 18.3 | 15.1 | 16.9 | n.s. |
SUSTAINED ATTENTION | ||||||||||
RVP (% of errors) | 24.2 | 12 | 15.9 | 9.6 | 0.03 | 16.8 | 9.5 | 13.2 | 9.4 | n.s. |
SHORT-TERM MEMORY | ||||||||||
Digit span | 5.9 | 0.9 | 5.9 | 1.1 | n.s. | 6.2 | 0.8 | 6.5 | 0.9 | n.s. |
Corsi Block span | 5.9 | 1.0 | 5.0 | 1.1 | 0.01 | 5.3 | 0.8 | 5.6 | 0.9 | n.s. |
(opposite to expected) | ||||||||||
MEMORY and LEARNING | ||||||||||
Rey Auditory Verbal Learning | ||||||||||
Trial A1–A5 (% errors) | 20.8 | 8.8 | 19.7 | 6.1 | n.s. | 24.5 | 11.4 | 21.7 | 9.3 | n.s. |
Delayed Recall (% errors) | 10.2 | 11 | 4.9 | 7.0 | 0.08 | 18.6 | 18 | 14.7 | 14.8 | n.s. |
Paired Associate Visual learning (% errors) | 2.3 | 2.2 | 1.2 | 1.3 | 0.07 | 2.5 | 3 | 1.8 | 1.8 | n.s. |
Italian AwPK Z Score | English AwPKU Z Score | Diff. | |||
---|---|---|---|---|---|
DOMAIN/TASK | Mean | SD | Mean | SD | p |
IQ | 1.0 | 1.0 | 0.9 | 1.0 | n.s. |
VISUO-SPATIAL ATTENTION RTs | |||||
Simple Detection—ms | 0.2 | 1.0 | 0.5 | 1.0 | n.s. |
Detention with Distractors—ms | 1.3 | 2.1 | 0.8 | 1.0 | n.s. |
Feature Search—ms | 1.5 | 2.3 | 1.3 | 1.6 | n.s. |
Conjunction Search ms | 1.1 | 1.2 | 1.2 | 1.2 | n.s. |
VISUAL ATTENTION accuracy | |||||
Detention with Distractors—% errors | 0.2 | 0.6 | 0.5 | 1.3 | n.s. |
Feature Search—% errors | 0.9 | 4.0 | −0.2 | 1.1 | n.s. |
Conjunction Search—% errors | 0.1 | 1.0 | −0.3 | 0.4 | n.s. |
VISUO-MOTOR COORDINATION | |||||
Pegboard—s | 0.7 | 1.2 | 1.0 | 1.6 | n.s. |
Digit Symbol—% errors in 90 s | 0.2 | 1.3 | 0.9 | 1.1 | n.s. |
Trail-Making Test A—s | 0.2 | 1.2 | 1.0 | 1.9 | n.s. |
EXECUTIVE FUNCTIONS | |||||
WCST | |||||
Total errors | 0.0 | 1.3 | 0.3 | 1.5 | n.s. |
Perseverative responses | −0.3 | 0.8 | 0.1 | 1.0 | n.s. |
N of Completed Categories | 0.1 | 1.0 | 0.3 | 1.3 | n.s. |
Trail-Making Tests | |||||
B (s) | 1.3 | 1.7 | −0.1 | 0.7 | <0.001# |
B–A (s) | 1.8 | 2.2 | −0.3 | 0.6 | <0.001# |
Verbal Fluency | |||||
Letter (correct answers) | 0.9 | 1.1 | 0.3 | 0.8 | 0.05 |
Semantic (correct answers) | 1.0 | 1.3 | 0.7 | 1.2 | n.s. |
Rey Auditory Verbal Learning | |||||
Retention after interference (% errors A6) | 1.1 | 1.7 | 0.3 | 1.0 | 0.07 |
SUSTAINED ATTENTION | |||||
RVP (% of errors) | 0.9 | 1.3 | 0.4 | 1.0 | n.s. |
SHORT-TERM MEMORY | |||||
Digit span | 0.0 | 0.8 | 0.3 | 0.9 | n.s. |
Corsi Block span | −0.8 | 0.9 | 0.3 | 0.9 | <0.001# |
LEARNING | |||||
Rey Auditory Verbal Learning Test | |||||
Trial A1–A5—% errors | 0.2 | 1.4 | 0.3 | 1.2 | n.s. |
Delayed Recall—% errors | 0.8 | 1.5 | 0.3 | 1.2 | n.s. |
Paired Associate Visual learning—% err | 0.9 | 1.7 | 0.4 | 1.7 | n.s. |
OVERALL Z SCORE excluding IQ | |||||
mean | 0.59 | 0.42 | n.s. | ||
SD | 0.76 | 0.58 |
VISUAL ATTENTION SPEED | VISUO-MOTOR | EF-MONITORING | SUST. | LEARNING AND MEMORY | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ITALIAN PKU | FSIQ | Simple | Detection | Feature | Conj. | Peg-Board | Digit | WCST | TMT | Digit | Corsi | Sem | ATTENT | Rey | Rey | Paired Ass. |
PHE | RT | With distractors RT | Search RT | Search RT | Sec. | Symbol | Total err | b–a | Span | Span | Fluency | RVP % | Words a1–a5 | Words Delayed | Visual Learning | |
0–10 yrs | ||||||||||||||||
Average | 0.38 | 0.43 | 0.42 | 0.15 | 0.30 | 0.05 | 0.28 | 0.19 | 0.55 * | 0.57 * | 0.37 | 0.03 | 0.43 | 0.17 | 0.08 | 0.30 |
SD | 0.31 | 0.73 ** | 0.73 ** | 0.34 | 0.49 * | 0.02 | 0.13 | −0.10 | 0.55 * | 0.66 ** | 0.42 | 0.08 | 0.57 * | 0.34 | 0.25 | 0.36 |
11–16 yrs | ||||||||||||||||
Average | 0.53 * | 0.08 | 0.30 | 0.41 | 0.35 | 0.18 | 0.38 | 0.28 | 0.44 | 0.32 | 0.29 | 0.41 | 0.63 ** | 0.14 | 0.08 | 0.49 * |
SD | 0.02 | 0.29 | 0.32 | 0.37 | 0.20 | −0.25 | −0.10 | −0.08 | 0.20 | 0.16 | −0.04 | 0.38 | 0.37 | −0.18 | −0.29 | 0.30 |
17 yr to now | ||||||||||||||||
Average | 0.58 ** | 0.03 | 0.37 | 0.38 | 0.41 | 0.32 | 0.60 ** | 0.59 ** | 0.56 * | 0.60 ** | 0.60 ** | 0.24 | 0.48 * | 0.11 | 0.09 | 0.30 |
SD | 0.52 * | −0.06 | 0.06 | 0.16 | 0.22 | 0.29 | 0.43 | 0.46 * | 0.52 * | 0.38 | 0.28 | 0.21 | 0.33 | 0.05 | −0.11 | −0.20 |
Current | 0.41 | −0.10 | 0.05 | 0.03 | 0.01 | 0.12 | 0.61 ** | 0.58 ** | 0.54 * | 0.60 ** | 0.37 | 0.00 | 0.30 | 0.21 | 0.16 | 0.11 |
Lifetime | ||||||||||||||||
Average | 0.55 * | 0.23 | 0.42 | 0.29 | 0.39 | 0.03 | 0.37 | 0.31 | 0.55 * | 0.58 ** | 0.33 | 0.23 | 0.58 * | 0.12 | 0.12 | 0.38 |
SD | 0.47 * | 0.45 | 0.54 * | 0.40 | 0.45 | 0.05 | 0.24 | 0.16 | 0.60 * | 0.55 * | 0.35 | 0.28 | 0.58 * | 0.13 | 0.00 | 0.26 |
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Romani, C.; Manti, F.; Nardecchia, F.; Valentini, F.; Fallarino, N.; Carducci, C.; De Leo, S.; MacDonald, A.; Palermo, L.; Leuzzi, V. Cognitive Outcomes and Relationships with Phenylalanine in Phenylketonuria: A Comparison between Italian and English Adult Samples. Nutrients 2020, 12, 3033. https://doi.org/10.3390/nu12103033
Romani C, Manti F, Nardecchia F, Valentini F, Fallarino N, Carducci C, De Leo S, MacDonald A, Palermo L, Leuzzi V. Cognitive Outcomes and Relationships with Phenylalanine in Phenylketonuria: A Comparison between Italian and English Adult Samples. Nutrients. 2020; 12(10):3033. https://doi.org/10.3390/nu12103033
Chicago/Turabian StyleRomani, Cristina, Filippo Manti, Francesca Nardecchia, Federica Valentini, Nicoletta Fallarino, Claudia Carducci, Sabrina De Leo, Anita MacDonald, Liana Palermo, and Vincenzo Leuzzi. 2020. "Cognitive Outcomes and Relationships with Phenylalanine in Phenylketonuria: A Comparison between Italian and English Adult Samples" Nutrients 12, no. 10: 3033. https://doi.org/10.3390/nu12103033
APA StyleRomani, C., Manti, F., Nardecchia, F., Valentini, F., Fallarino, N., Carducci, C., De Leo, S., MacDonald, A., Palermo, L., & Leuzzi, V. (2020). Cognitive Outcomes and Relationships with Phenylalanine in Phenylketonuria: A Comparison between Italian and English Adult Samples. Nutrients, 12(10), 3033. https://doi.org/10.3390/nu12103033