A test of the frontal‐specificity hypothesis in the cognitive performance of adults with phenylketonuria

Smith, Mary Lou; Klim, Paula; Mallozzi, Elfio; Hanley, William

doi:10.1080/87565649609540656

Cited by 35 publications

(48 citation statements)

References 25 publications

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“…For example, deficits in working memory (White, Nortz, Mandernach, Huntington, & Steiner, 2002), inhibitory control (Diamond, 1994;Stemerdink et al, 1999), conceptual reasoning (Leuzzi et al, 2004;Smith, Klim, & Hanley, 2000;Stemerdink et al, 1999), planning ability (Leuzzi et al, 2004;, selective and sustained attention Schmidt, Burgard, & Rupp, 1996;Weglage, Pietsch, Fünders, Koch, & Ullrich, 1996), mental flexibility (Diamond, Prevor, Callender, & Druin, 1997;, and organizational strategy (White, Nortz, Mandernach, Huntington, & Steiner, 2001) have been identified in this population. Furthermore, a number of studies have found executive skills to be poorer in children with higher concurrent PHE levels (Diamond, 1994;Schmidt et al, 1996;Smith, Klim, Mallozzi, & Hanley, 1996;Weglage et al, 1996;, consistent with the premise that these deficits are associated with dopamine depletion. In many cases, dietary restriction of PHE is either discontinued or relaxed during adolescence, and according to the prefrontal dysfunction hypothesis, executive impairments should increase at this time.…”

Section: Prefrontal Dysfunction Hypothesismentioning

confidence: 61%

“…In many cases, dietary restriction of PHE is either discontinued or relaxed during adolescence, and according to the prefrontal dysfunction hypothesis, executive impairments should increase at this time. In agreement with this rationale, working memory deficits have been shown to increase with age (White et al, 2002), and executive impairments have been identified in adults with early-treated PKU (Brumm et al, 2004;Channon et al, 2004;Ris, Williams, Hunt, Berry, & Leslie, 1994;Smith et al, 1996).…”

Section: Prefrontal Dysfunction Hypothesismentioning

confidence: 73%

“…A double blind crossover randomized controlled trial of TYR supplementation indicated that this intervention provides no cognitive benefits (Smith et al, 1998), however this may be due to the minimal impact TYR supplementation had on the PHE to TYR ratio, which in turn, influences the transportation of LNAAs across the BBB (Kalsner, Rohr, Strauss, Korson, & Levy, 2001). Finally, research with this population has also indicated slow reaction times (Feldmann et al, 2002;Schmidt et al, 1994), compromised interhemispheric transfer (Banich, Passarotti, White, Nortz, & Steiner, 2000;Gourovitch, Craft, Dowton, Ambrose, & Sparts, 1994), memory problems (Brumm et al, 2004;Smith et al, 2000;Smith et al, 1996), language deficits (Brumm et al, 2004), perceptual difficulties (Smith et al, 1996), and mild neurological impairment (Burlina et al, 2000;Weglage, Pietsch, Funders, Koch, & Ullrich, 1995). Clearly executive dysfunction is not the sole cognitive impairment exhibited by children with early-treated PKU, and the impact of basic cognitive processes such as speed of processing, interhemispheric transfer, and perceptual abilities on executive functioning in this population is yet to be determined.…”

Section: Prefrontal Dysfunction Hypothesismentioning

confidence: 93%

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Are Neuropsychological Impairments in Children with Early-Treated Phenylketonuria (PKU) Related to White Matter Abnormalities or Elevated Phenylalanine Levels?

Anderson

Wood

Francis

et al. 2007

Developmental Neuropsychology

120

101

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This study aimed to enhance our understanding of neuropsychological functioning in children with early-treated phenylketonuria (PKU) and assess the relative impact of white matter abnormalities (WMA) and neurotransmitter deficiencies on cognitive functions in this population. The study consisted of 33 children with early-treated PKU and 34 healthy control children aged between 7 to 18 years. All children had a neuropsychological evaluation that included measures of general intelligence, attention, processing speed, memory and learning, executive function, and academic achievement. Children in the PKU group also had a magnetic resonance (MR) brain scan. When compared with the control group, the PKU group exhibited global cognitive impairment including lower IQ, attention problems, slow information processing, reduced learning capacity, mild executive impairments, and educational difficulties. Children in the PKU group with extensive WMA (n = 14) displayed significant impairments across all cognitive domains. Metabolic control correlated weakly to moderately with attention, executive, and memory/learning factors. Within the PKU group, regressions revealed that executive function and attention factors were independently related to severity of WM pathology and age, while the memory and learning factor was independently related to metabolic control and age. It is concluded that children with early-treated PKU exhibit a global pattern of impairment, with a particular deficit in processing speed. WM pathology extending into frontal and subcortical regions correlates with the greatest deficits and a profile of impairment consistent with diffuse WM damage. Our findings also offer some support for dopamine depletion in the prefrontal cortex, however adverse consequences as a result of norepinephrine and serotonin deficiencies should not be discounted.

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Section: Prefrontal Dysfunction Hypothesismentioning

confidence: 61%

Section: Prefrontal Dysfunction Hypothesismentioning

confidence: 73%

Section: Prefrontal Dysfunction Hypothesismentioning

confidence: 93%

See 1 more Smart Citation

Are Neuropsychological Impairments in Children with Early-Treated Phenylketonuria (PKU) Related to White Matter Abnormalities or Elevated Phenylalanine Levels?

Anderson

Wood

Francis

et al. 2007

Developmental Neuropsychology

120

101

View full text Add to dashboard Cite

show abstract

“…Experimental studies with nonhuman primates have shown that dopamine depletion in the prefrontal cortex has a functional impact resulting in poorer performance of executive skills such as working memory (Sawaguchi and Goldman-Rakic 1991). Similar executive dysfunction has been described in children with ETPKU (Welsh et al 1990, Smith et al 1996, Diamond et al 1997, Stemerdink et al 1999, White et al 2001, Huijbregts et al 2002, providing further support for the dopamine depletion hypothesis.…”

Section: Discussionmentioning

confidence: 88%

Neuropsychological functioning in children with early-treated phenylketonuria: impact of white matter abnormalities

Anderson

Wood

Francis

et al. 2004

Dev Med Child Neurol

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Impact of white matter abnormalities (WMAs) on neuropsychological functioning in children with early-treated phenylketonuria (ETPKU) was examined. Children with ETPKU (20 males, 12 females, mean age 11 years 2 months, SD 3 years 6 months) and controls (20 males, 14 females, mean age 10 years 4 months, SD 3 years 1 month) aged 7 to 18 years were assessed using tests of attention, processing speed, memory and learning, executive function, and academic achievement. Those with ETPKU, exhibiting WMAs extending into subcortical/frontal regions (n=14), displayed significant impairments in a number of domains. Children with ETPKU but no WMAs (n=6), or pathology restricted to the posterior periventricular region (n=12), displayed only mild deficits. Concurrent phenylalanine levels correlated weakly with cognitive parameters, whereas lifetime phenylalanine levels were associated with deficits in several cognitive domains. Impairments in children with extensive WMAs are consistent with compromised neural transmission, which is characterized by dysmyelination. However, children with no detectable, or mild WMAs, also displayed cognitive problems, indicating that neuropsychological functioning in children with ETPKU is determined by a complex interaction of biological and environmental factors.

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“…The degree of deficits in PKU has often been associated with concurrent and historical Phe levels (Diamond et al, 1997;Smith et al, 1996). High Phe levels during critical age periods may interfere with the development of cognitive abilities.…”

Section: Developmental Time Tables Of Processing Speed and Aspects Ofmentioning

confidence: 99%

Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria.

et al. 2003

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This study examined motor control in 61 early and continuously treated patients with phenylketonuria (PKU) and 69 control participants, aged 7 to 14 years. The pursuit task demanded concurrent planning and execution of unpredictable movements, whereas the tracking task required a highly automated circular movement that could be planned in advance. PKU patients showed significantly poorer motor control in both tasks compared with control participants. Deficits were particularly observed for younger patients (age Ͻ 11 years). Differences between control participants and PKU patients were significantly greater in the pursuit task compared with the tracking task, indicating more serious deficits when a higher level of controlled processing is required. Correlations with historical phenylalanine levels indicated a later maturation of the level of control required by the pursuit task compared with the tracking task.

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A test of the frontal‐specificity hypothesis in the cognitive performance of adults with phenylketonuria

Cited by 35 publications

References 25 publications

Are Neuropsychological Impairments in Children with Early-Treated Phenylketonuria (PKU) Related to White Matter Abnormalities or Elevated Phenylalanine Levels?

Are Neuropsychological Impairments in Children with Early-Treated Phenylketonuria (PKU) Related to White Matter Abnormalities or Elevated Phenylalanine Levels?

Neuropsychological functioning in children with early-treated phenylketonuria: impact of white matter abnormalities

Motor function under lower and higher controlled processing demands in early and continuously treated phenylketonuria.

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