Laura Hokkanen | University of Helsinki (original) (raw)

Papers by Laura Hokkanen

Scandinavian Journal of Medicine & Science in Sports, 2014

The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye move... more The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye movements, has shown promise as a supplemental screening test following concussion. However, limited normative data for this test have been published.The K-D test was administered to 185 professional ice hockey players as a preseason baseline test in seasons 2012-2013 and 2013-2014. Their average age was 23.8 years (median = 22.0 years, range = 16-40 years). The average K-D score was 40.0 s (SD = 6.1 s, range = 24.0-65.7 s). K-D test performance showed no association with age, education, or the number of self-reported previous concussions in this sample. The association between trials 1 and 2 of the K-D test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K-D test for professional male ice hockey players are reported. K-D test performance did not vary by age, education, or concussion history in this study.

Auditory evoked responses and spontaneous cortical activity were recorded with a whole-scalp 122-... more Auditory evoked responses and spontaneous cortical activity were recorded with a whole-scalp 122-channel neuromagnetometer from 7 patients, who had small thalamic infarctions in the region of the left anterior tuberothalamic artery and associated memory defects. In contrast to healthy control subjects, with dominant rhythmic activity at 10.6 ± 0.6 Hz in the parieto-occipital region, the spectral maximum in the patients was at 8.9 ± 0.4 Hz. Abnormal acceleration of rhythmic activity was also observed bilaterally in rolandic areas. Our findings imply that lesions of non-specific thalamic nuclei may disturb human brain rhythms in widespread cortical areas. 'Mismatch responses' to deviant tones (1.1 kHz) among standards (1.0 kHz), suggested to reflect sensory auditory memory in healthy subjects, were absent in 2 patients, markedly decreased in 3, and normal in 2, implying that pathways passing through the anteromedial thalamus contribute to modulation of these responses. We conclude that local unilateral lesions in the anteromedial thalamus may cause extensive, bilateral alterations in the brain's electric activity.

Cerebrovascular Diseases, 1994

The long-term prognosis after left tuberothalamic infarction was studied in a selected group of 7... more The long-term prognosis after left tuberothalamic infarction was studied in a selected group of 7 patients who had memory disturbances sufficiently severe to warrant neuropsychological consultation and rehabilitation. The mean age of the patients was 46.7 ± 5.6 years and the mean follow-up time 22.3 ± 15.0 months. At the acute stage 4 patients had dysphasia, 1 hemiparesis, and 1

PeerJ, 2014

Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyl... more Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the...

Electroencephalography and Clinical Neurophysiology, 1998

Spontaneous cortical activity and auditory evoked responses were recorded with a whole-scalp 122-... more Spontaneous cortical activity and auditory evoked responses were recorded with a whole-scalp 122-channel neuromagnetometer from 4 patients after left-hemisphere dominant herpes simplex encephalitis and associated memory disorders. Spontaneous activity of one patient contained periodic sharp waves over the left hemisphere; the background activity was attenuated. The sources of periodic sharp waves clustered close to the sources of auditory evoked fields in the temporal lobe. In controls, dominant rhythmic activity over the parieto-occipital region had spectral maximum at 10.6 +/- 0.6 Hz; in patients the dominant rhythmic activity peaked at 8.6 +/- 1.8 Hz. The suppression of the parieto-occipital activity in eyes-open versus eyes-closed condition was smaller in patients than in controls. The patients' peak spectral frequency was correlated with neuropsychological tests reflecting deficient attentional capacity. The observed changes probably reflect decreased subcortical control of the cortical electric activity.

Neuropsychology Review, 2000

Acute encephalitis is an inflammation of the brain parenchyma. In the USA, 20 000 cases occur yea... more Acute encephalitis is an inflammation of the brain parenchyma. In the USA, 20 000 cases occur yearly. A variety of cognitive deficits may persist after the acute stage, and they are often the sole cause of disability. Still, infectious diseases tend to be covered only briefly in neuropsychological handbooks. Recent literature demonstrates the heterogeneity of both mnestic disorders and the outcome following encephalitides. Herpes Simplex virus (HSV) is the most common single etiology of sporadic encephalitis and it usually causes the most severe symptoms. Modern antiviral medication, however, seems to improve the cognitive outcome. Much less is known about non-HSV encephalitides, where both mild and severe defects have been observed. This article summarizes the current knowledge and also calls upon a more active neuropsychological research in the area.

Prospective follow-up studies on long term effects of pre-and perinatal adverse conditions in adu... more Prospective follow-up studies on long term effects of pre-and perinatal adverse conditions in adulthood are rare. We will continue to follow the prospective cohort of initially 1196 subjects with predefined at-delivery risk factors out of 22,359 consecutive deliveries during 1971-74 at a single maternity hospital. The risk cohort and 93 controls have been followed up with a comprehensive clinical program at 5, 9, and 16 years of age and by questionnaire at the age of 30 years. Major medical events known to affect the development and growth of the brain, or cognitive functions and personality have been documented. Here we present a pre-protocol for the project, which we will call PLASTICITY, whose aim is to follow consenting subjects and controls into mid-adulthood and beyond, and to explore how the neonatal risk factors modulate neurodevelopmental and neurodegenerative processes such as learning disabilities, ADHD, aging, early onset mild cognitive impairment and even dementia. Our first focus is on the neurological and cognitive outcomes at age 40 years, using detailed neurological, neuropsychological, neuroimaging, genetic, blood chemistry and registry based methods. Results will be expected to offer information on the risk of neurological, psychiatric, metabolic and other medical consequences as well as the need for health and social services at the brink of middle age, when new degenerative phenomena are known to emerge. The evaluation at age 40 years will serve as a baseline for later aging studies. We welcome all comments and suggestions, which we will apply in finalizing details and inviting collaboration.

Background. Attrition is a major cause of potential bias in longitudinal studies and clinical tri... more Background. Attrition is a major cause of potential bias in longitudinal studies and clinical trials. Attrition rate above 20% raises concern of the reliability of the results. Few studies have looked at the factors behind attrition in follow-ups spanning decades. Methods. We analyzed attrition and associated factors of a 30-year follow-up cohort of subjects who were born with perinatal risks for neurodevelopmental disorders. Attrition rates were calculated at different stages of follow-up and differences between responders and non-responders were tested. To find combinations of variables influencing attrition and investigate their relative importance at birth, 5, 9, 16 and 30 years of follow-up we used the random forest classification. Results. Initial loss of potential participants was 13%. Attrition was 16% at five, 24% at nine, 35% at 16 and 46% at 30 years. The only group difference that emerged between responders and non-responders was in socioeconomic status (SES). The variables identified by random forest classification analysis were classified into Birth related, Development related and SES related. Variables from all these categories contributed to attrition, but SES related variables were less important than birth and development associated variables. Classification accuracy ranged between 0.74 and 0.96 depending on age. Discussion. Lower SES is linked to attrition in many studies. Our results point to the importance of the growth and development related factors in a longitudinal study. Parents' decisions to participate depend on the characteristics of the child. The same association was also seen when the child, now grown up, decided to participate at 30 years. In addition, birth related medical variables are associated with the attrition still at the age of 30. Our results using a data mining approach suggest that attrition in longitudinal studies is influenced by complex interactions of a multitude of variables, which are not necessarily evident using other multivariate techniques.

Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious co... more Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood. Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrations > 340 µmol/l or required blood exchange transfusion. Subjects with HB were divided into subgroups based on the presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral disorders in childhood, and compared with healthy controls. Subjects were seen at discharge, 5, 9 and 16 years of life and parent's and teacher's assessments were recorded. At 30 years they filled a questionnaire about academic and occupational achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading and writing tests at 9 years of life. Results. Compared to controls, the odds for a child with HB having neurobehavioral symptoms at 9 years was elevated (OR = 4.68). Forty-five per cent of the HB group were affected by cognitive abnormalities in childhood and continued to experience problems in adulthood. This was apparent in academic achievement (p < 0.0001) and the ability to complete secondary (p < 0.0001) and tertiary (p < 0.004) education. Also, the subgroup of affected HB reported persisting cognitive complaints e.g., problems with reading, writing and mathematics. Childhood symptoms of hyperactivity/impulsivity (p < 0.0001) and inattention (p < 0.02) were more common in HB groups, but in adulthood the symptoms were equal. The affected HB had lower scores in parameters reflecting life satisfaction, less controlled drinking, but not increased substance abuse. Discussion. Our results indicate that neonatal HB has negative consequences in adult age. A prospectively collected cohort with strict inclusion criteria enables to control most of the bias factors involved with retrospective data. The control and HB groups were remarkably similar at birth in terms of medical data, and the How to cite this article Hokkanen et al. (2014), Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates-a 30 year prospective follow-up study. PeerJ 2:e294; DOI 10.7717/peerj.294 Subjects

Longitudinal follow-up of ADHD suggests a poorer outcome in those affected. Studies extending to ... more Longitudinal follow-up of ADHD suggests a poorer outcome in those affected. Studies extending to 30 years however are rare. We investigated the adult outcome of ADHD associated with perinatal risks (PRs), treated non-pharmacologically. A study group of 122 participants (86 men, 36 women) with PR-associated ADHD was followed-up from birth and compared with a control group also prospectively studied. The study group showed more cognitive, motor perception, and learning impairments as well as psychiatric problems at ages 5, 9, and 16. At age 30, the study group reported less education, more involuntary job dismissals and more alcohol abuse. Self-reported ADHD symptoms were still prevalent in adulthood. ADHD symptoms persist and impair the long-term educational, occupational, and psychiatric outcome. ADHD in participants with PR appears to follow a course seen in studies of unselected ADHD.

Scandinavian Journal of Medicine & Science in Sports, 2014

The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye move... more The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye movements, has shown promise as a supplemental screening test following concussion. However, limited normative data for this test have been published.The K-D test was administered to 185 professional ice hockey players as a preseason baseline test in seasons 2012-2013 and 2013-2014. Their average age was 23.8 years (median = 22.0 years, range = 16-40 years). The average K-D score was 40.0 s (SD = 6.1 s, range = 24.0-65.7 s). K-D test performance showed no association with age, education, or the number of self-reported previous concussions in this sample. The association between trials 1 and 2 of the K-D test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K-D test for professional male ice hockey players are reported. K-D test performance did not vary by age, education, or concussion history in this study.

Annals of Dyslexia, 2013

In this study of the project DyAdd, implicit learning was investigated through two paradigms in a... more In this study of the project DyAdd, implicit learning was investigated through two paradigms in adults (18-55 years) with dyslexia (n = 36) or with attention deficit/hyperactivity disorder (ADHD, n = 22) and in controls (n = 35). In the serial reaction time (SRT) task, there were no group differences in learning. However, those with ADHD exhibited faster RTs compared to other groups. In the artificial grammar learning (AGL) task, the groups did not differ from each other in their learning (i.e., grammaticality accuracy or similarity choices). Further, all three groups were sensitive to fragment overlap between learning and test-phase items (i.e., similarity choices were above chance). Grammaticality performance of control participants was above chance, but that of participants with dyslexia and participants with ADHD failed to differ from chance, indicating impaired grammaticality learning in these groups. While the main indices of AGL performance, grammaticality accuracy and similarity choices did not correlate with the neuropsychological variables that reflected dyslexia-related (phonological processing, reading, spelling, arithmetic) or ADHD-related characteristics (executive functions, attention), or intelligence, the explicit knowledge for the AGL grammar (i.e., ability to freely generate grammatical strings) correlated positively with the variables of phonological processing and reading. Further, SRT reaction times correlated positively with full scale intelligence quotient (FIQ). We conclude that, in AGL, learning difficulties of the underlying rule structure (as measured by grammaticality) are associated with dyslexia and ADHD. However, learning in AGL is not related to the defining neuropsychological features of dyslexia or ADHD. Instead, the resulting explicit knowledge relates to characteristics of dyslexia.

Twin Research and Human Genetics, 2010

Psychological Science, 2010

Psychological Medicine, 1995

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2009

In project DyAdd, we compared the fatty acid (FA) profiles of serum phospholipids in adults with ... more In project DyAdd, we compared the fatty acid (FA) profiles of serum phospholipids in adults with attention deficit hyperactivity disorder (ADHD) (n=26), dyslexia (n=36), their comorbid combination (n=9), and healthy controls (n=36). FA proportions were analyzed in a 2x2 design with Bonferroni corrected post hoc comparisons. A questionnaire was used to assess dietary fat quality and use of supplements. Results showed that ADHD and dyslexia were not associated with total saturated FAs, monounsaturated FAs, or n-3 polyunsaturated FAs (PUFAs). However, those with ADHD had elevated proportions of total n-6 PUFAs (including gamma-linolenic and adrenic acids) as compared to those without ADHD. Dyslexia was related to a higher proportion of monounsaturated nervonic acid and a higher ratio of n-6/n-3 PUFAs. Among females none of the associations were significant. However in males, all the original associations observed in all subjects remained and ADHD was associated with elevated nervonic acid and n-6/n-3 PUFA ratio like dyslexia. Controlling for poorly diagnosed reading difficulties, education, dietary fat quality, or use of FA supplements did not generally remove the originally observed associations.

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2009

Both attention deficit hyperactivity disorder (ADHD) and dyslexia are suggested to co-occur with ... more Both attention deficit hyperactivity disorder (ADHD) and dyslexia are suggested to co-occur with altered fatty acid (FA) metabolism, but it is unknown how FAs are associated with the cognitive domains that characterize these disorders. In the project DyAdd, we investigated the associations between FAs in serum phospholipids and phonological processing, reading, spelling, arithmetic, executive functions, and attention. Healthy controls (n=36), adults with ADHD (n=26), dyslexia (n=36), or both (n=9) were included in the study. FAs included saturated, monounsaturated, total polyunsaturated, n-3, and n-6 FAs, together with n-6/n-3, AA/EPA, and LA/ALA ratios. When all the study subjects were included in the analyses, especially polyunsaturated FAs (PUFAs) were positively associated with cognition, but reading was least associated with FAs. These associations were modulated by gender, intelligence, n-3 PUFA intake, and group. Accordingly, within the ADHD group, only few associations emerged with PUFAs, n-6 PUFAs, and cognitive domains, whereas in the dyslexia group the more prevalent associations appeared with PUFAs and n-3 PUFAs.

Pharmacology Biochemistry and Behavior, 1994

The cognitive effects of high-dose human leukocyte alpha-interferon (IFN-alpha) treatment were ev... more The cognitive effects of high-dose human leukocyte alpha-interferon (IFN-alpha) treatment were evaluated among 15 patients with the newly diagnosed spinal form of amyotrophic lateral sclerosis (ALS). To confirm the earlier findings showing reversible effects on cognitive performance and to exclude confounding effects, a randomized blinded placebo controlled study was conducted. Twelve patients with continuous intravenous IFN-alpha-infusion treatment over five days and 3 placebo control patients were neuropsychologically evaluated. The neuropsychological examination included tests of intelligence, memory, complex mental processing, visuoconstructional skills, writing, and calculation. A clear difference in the performance profiles of the placebo and the IFN-alpha-treated patient groups was detected: The IFN-alpha group showed significant deterioration during treatment in the digit span backwards task, logical verbal memory task, calculation ability, and writing time, while improvement was seen after treatment. Concomitant fever did not explain the findings. In the placebo group an improvement indicating a learning effect in the three consecutive measurements was found. The reversible cognitive deterioration indicates a clear CNS effect during the IFN-alpha treatment.

Parkinsonism & Related Disorders, 2008

Cognitive dysfunction is common in Parkinson&amp;amp;#39;s disease (PD). Low plasma uric acid... more Cognitive dysfunction is common in Parkinson&amp;amp;#39;s disease (PD). Low plasma uric acid level is a risk factor for PD but its association with cognitive impairment in PD has not been previously studied. In the present study urine uric acid level as well as plasma uric acid- and homocysteine levels were measured in 40 patients with PD. Comprehensive neuropsychological tests including computerized tasks were performed on all. Both low plasma and low urine uric acid levels associated with decreased neuropsychological performance. In multiple linear regression low urine uric acid level predicted worse performance in the Picture completion subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (p=0.003) and in the Rule shift cards test of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) (p=0.04). Low plasma uric acid level predicted worse performance both in the Picture completion (p=0.02) and Similarities subtest of the WAIS-R (p=0.02). Reaction time and the time spent on cognitive processing in the Statement verification task were inversely correlated with the uric acid levels (p=0.0001). There was no correlation between the homocysteine level and neuropsychological performance. Instead, the plasma uric acid and homocysteine levels correlated significantly and their possible association in PD is discussed.

Scandinavian Journal of Medicine & Science in Sports, 2014

The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye move... more The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye movements, has shown promise as a supplemental screening test following concussion. However, limited normative data for this test have been published.The K-D test was administered to 185 professional ice hockey players as a preseason baseline test in seasons 2012-2013 and 2013-2014. Their average age was 23.8 years (median = 22.0 years, range = 16-40 years). The average K-D score was 40.0 s (SD = 6.1 s, range = 24.0-65.7 s). K-D test performance showed no association with age, education, or the number of self-reported previous concussions in this sample. The association between trials 1 and 2 of the K-D test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K-D test for professional male ice hockey players are reported. K-D test performance did not vary by age, education, or concussion history in this study.

Auditory evoked responses and spontaneous cortical activity were recorded with a whole-scalp 122-... more Auditory evoked responses and spontaneous cortical activity were recorded with a whole-scalp 122-channel neuromagnetometer from 7 patients, who had small thalamic infarctions in the region of the left anterior tuberothalamic artery and associated memory defects. In contrast to healthy control subjects, with dominant rhythmic activity at 10.6 ± 0.6 Hz in the parieto-occipital region, the spectral maximum in the patients was at 8.9 ± 0.4 Hz. Abnormal acceleration of rhythmic activity was also observed bilaterally in rolandic areas. Our findings imply that lesions of non-specific thalamic nuclei may disturb human brain rhythms in widespread cortical areas. 'Mismatch responses' to deviant tones (1.1 kHz) among standards (1.0 kHz), suggested to reflect sensory auditory memory in healthy subjects, were absent in 2 patients, markedly decreased in 3, and normal in 2, implying that pathways passing through the anteromedial thalamus contribute to modulation of these responses. We conclude that local unilateral lesions in the anteromedial thalamus may cause extensive, bilateral alterations in the brain's electric activity.

Cerebrovascular Diseases, 1994

The long-term prognosis after left tuberothalamic infarction was studied in a selected group of 7... more The long-term prognosis after left tuberothalamic infarction was studied in a selected group of 7 patients who had memory disturbances sufficiently severe to warrant neuropsychological consultation and rehabilitation. The mean age of the patients was 46.7 ± 5.6 years and the mean follow-up time 22.3 ± 15.0 months. At the acute stage 4 patients had dysphasia, 1 hemiparesis, and 1

PeerJ, 2014

Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyl... more Hereditary gelsolin amyloidosis (AGel amyloidosis) is an autosomal dominant form of systemic amyloidosis caused by a c.640G>A or c.640G>T mutation in the gene coding for gelsolin. Principal clinical manifestations include corneal lattice dystrophy, cranial neuropathy and cutis laxa with vascular fragility. Signs of minor CNS involvement have also been observed, possibly related to cerebral amyloid angiopathy (CAA). To investigate further if AGel amyloidosis carries a risk for a specific neuropsychological or psychiatric symptomatology we studied 35 AGel patients and 29 control subjects. Neuropsychological tests showed abnormalities in visuocontructional and -spatial performance in AGel patients, also some indication of problems in processing efficacy was found. At psychiatric evaluation the patient group showed more psychiatric symptomatology, mainly depression. In brain MRI, available in 16 patients and 14 controls, we found microhemorrhages or microcalcifications only in the...

Electroencephalography and Clinical Neurophysiology, 1998

Spontaneous cortical activity and auditory evoked responses were recorded with a whole-scalp 122-... more Spontaneous cortical activity and auditory evoked responses were recorded with a whole-scalp 122-channel neuromagnetometer from 4 patients after left-hemisphere dominant herpes simplex encephalitis and associated memory disorders. Spontaneous activity of one patient contained periodic sharp waves over the left hemisphere; the background activity was attenuated. The sources of periodic sharp waves clustered close to the sources of auditory evoked fields in the temporal lobe. In controls, dominant rhythmic activity over the parieto-occipital region had spectral maximum at 10.6 +/- 0.6 Hz; in patients the dominant rhythmic activity peaked at 8.6 +/- 1.8 Hz. The suppression of the parieto-occipital activity in eyes-open versus eyes-closed condition was smaller in patients than in controls. The patients&amp;amp;amp;amp;#39; peak spectral frequency was correlated with neuropsychological tests reflecting deficient attentional capacity. The observed changes probably reflect decreased subcortical control of the cortical electric activity.

Neuropsychology Review, 2000

Acute encephalitis is an inflammation of the brain parenchyma. In the USA, 20 000 cases occur yea... more Acute encephalitis is an inflammation of the brain parenchyma. In the USA, 20 000 cases occur yearly. A variety of cognitive deficits may persist after the acute stage, and they are often the sole cause of disability. Still, infectious diseases tend to be covered only briefly in neuropsychological handbooks. Recent literature demonstrates the heterogeneity of both mnestic disorders and the outcome following encephalitides. Herpes Simplex virus (HSV) is the most common single etiology of sporadic encephalitis and it usually causes the most severe symptoms. Modern antiviral medication, however, seems to improve the cognitive outcome. Much less is known about non-HSV encephalitides, where both mild and severe defects have been observed. This article summarizes the current knowledge and also calls upon a more active neuropsychological research in the area.

Prospective follow-up studies on long term effects of pre-and perinatal adverse conditions in adu... more Prospective follow-up studies on long term effects of pre-and perinatal adverse conditions in adulthood are rare. We will continue to follow the prospective cohort of initially 1196 subjects with predefined at-delivery risk factors out of 22,359 consecutive deliveries during 1971-74 at a single maternity hospital. The risk cohort and 93 controls have been followed up with a comprehensive clinical program at 5, 9, and 16 years of age and by questionnaire at the age of 30 years. Major medical events known to affect the development and growth of the brain, or cognitive functions and personality have been documented. Here we present a pre-protocol for the project, which we will call PLASTICITY, whose aim is to follow consenting subjects and controls into mid-adulthood and beyond, and to explore how the neonatal risk factors modulate neurodevelopmental and neurodegenerative processes such as learning disabilities, ADHD, aging, early onset mild cognitive impairment and even dementia. Our first focus is on the neurological and cognitive outcomes at age 40 years, using detailed neurological, neuropsychological, neuroimaging, genetic, blood chemistry and registry based methods. Results will be expected to offer information on the risk of neurological, psychiatric, metabolic and other medical consequences as well as the need for health and social services at the brink of middle age, when new degenerative phenomena are known to emerge. The evaluation at age 40 years will serve as a baseline for later aging studies. We welcome all comments and suggestions, which we will apply in finalizing details and inviting collaboration.

Background. Attrition is a major cause of potential bias in longitudinal studies and clinical tri... more Background. Attrition is a major cause of potential bias in longitudinal studies and clinical trials. Attrition rate above 20% raises concern of the reliability of the results. Few studies have looked at the factors behind attrition in follow-ups spanning decades. Methods. We analyzed attrition and associated factors of a 30-year follow-up cohort of subjects who were born with perinatal risks for neurodevelopmental disorders. Attrition rates were calculated at different stages of follow-up and differences between responders and non-responders were tested. To find combinations of variables influencing attrition and investigate their relative importance at birth, 5, 9, 16 and 30 years of follow-up we used the random forest classification. Results. Initial loss of potential participants was 13%. Attrition was 16% at five, 24% at nine, 35% at 16 and 46% at 30 years. The only group difference that emerged between responders and non-responders was in socioeconomic status (SES). The variables identified by random forest classification analysis were classified into Birth related, Development related and SES related. Variables from all these categories contributed to attrition, but SES related variables were less important than birth and development associated variables. Classification accuracy ranged between 0.74 and 0.96 depending on age. Discussion. Lower SES is linked to attrition in many studies. Our results point to the importance of the growth and development related factors in a longitudinal study. Parents&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; decisions to participate depend on the characteristics of the child. The same association was also seen when the child, now grown up, decided to participate at 30 years. In addition, birth related medical variables are associated with the attrition still at the age of 30. Our results using a data mining approach suggest that attrition in longitudinal studies is influenced by complex interactions of a multitude of variables, which are not necessarily evident using other multivariate techniques.

Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious co... more Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood. Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n = 1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrations > 340 µmol/l or required blood exchange transfusion. Subjects with HB were divided into subgroups based on the presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral disorders in childhood, and compared with healthy controls. Subjects were seen at discharge, 5, 9 and 16 years of life and parent's and teacher's assessments were recorded. At 30 years they filled a questionnaire about academic and occupational achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading and writing tests at 9 years of life. Results. Compared to controls, the odds for a child with HB having neurobehavioral symptoms at 9 years was elevated (OR = 4.68). Forty-five per cent of the HB group were affected by cognitive abnormalities in childhood and continued to experience problems in adulthood. This was apparent in academic achievement (p < 0.0001) and the ability to complete secondary (p < 0.0001) and tertiary (p < 0.004) education. Also, the subgroup of affected HB reported persisting cognitive complaints e.g., problems with reading, writing and mathematics. Childhood symptoms of hyperactivity/impulsivity (p < 0.0001) and inattention (p < 0.02) were more common in HB groups, but in adulthood the symptoms were equal. The affected HB had lower scores in parameters reflecting life satisfaction, less controlled drinking, but not increased substance abuse. Discussion. Our results indicate that neonatal HB has negative consequences in adult age. A prospectively collected cohort with strict inclusion criteria enables to control most of the bias factors involved with retrospective data. The control and HB groups were remarkably similar at birth in terms of medical data, and the How to cite this article Hokkanen et al. (2014), Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates-a 30 year prospective follow-up study. PeerJ 2:e294; DOI 10.7717/peerj.294 Subjects

Longitudinal follow-up of ADHD suggests a poorer outcome in those affected. Studies extending to ... more Longitudinal follow-up of ADHD suggests a poorer outcome in those affected. Studies extending to 30 years however are rare. We investigated the adult outcome of ADHD associated with perinatal risks (PRs), treated non-pharmacologically. A study group of 122 participants (86 men, 36 women) with PR-associated ADHD was followed-up from birth and compared with a control group also prospectively studied. The study group showed more cognitive, motor perception, and learning impairments as well as psychiatric problems at ages 5, 9, and 16. At age 30, the study group reported less education, more involuntary job dismissals and more alcohol abuse. Self-reported ADHD symptoms were still prevalent in adulthood. ADHD symptoms persist and impair the long-term educational, occupational, and psychiatric outcome. ADHD in participants with PR appears to follow a course seen in studies of unselected ADHD.

Scandinavian Journal of Medicine & Science in Sports, 2014

The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye move... more The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye movements, has shown promise as a supplemental screening test following concussion. However, limited normative data for this test have been published.The K-D test was administered to 185 professional ice hockey players as a preseason baseline test in seasons 2012-2013 and 2013-2014. Their average age was 23.8 years (median = 22.0 years, range = 16-40 years). The average K-D score was 40.0 s (SD = 6.1 s, range = 24.0-65.7 s). K-D test performance showed no association with age, education, or the number of self-reported previous concussions in this sample. The association between trials 1 and 2 of the K-D test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K-D test for professional male ice hockey players are reported. K-D test performance did not vary by age, education, or concussion history in this study.

Annals of Dyslexia, 2013

In this study of the project DyAdd, implicit learning was investigated through two paradigms in a... more In this study of the project DyAdd, implicit learning was investigated through two paradigms in adults (18-55 years) with dyslexia (n = 36) or with attention deficit/hyperactivity disorder (ADHD, n = 22) and in controls (n = 35). In the serial reaction time (SRT) task, there were no group differences in learning. However, those with ADHD exhibited faster RTs compared to other groups. In the artificial grammar learning (AGL) task, the groups did not differ from each other in their learning (i.e., grammaticality accuracy or similarity choices). Further, all three groups were sensitive to fragment overlap between learning and test-phase items (i.e., similarity choices were above chance). Grammaticality performance of control participants was above chance, but that of participants with dyslexia and participants with ADHD failed to differ from chance, indicating impaired grammaticality learning in these groups. While the main indices of AGL performance, grammaticality accuracy and similarity choices did not correlate with the neuropsychological variables that reflected dyslexia-related (phonological processing, reading, spelling, arithmetic) or ADHD-related characteristics (executive functions, attention), or intelligence, the explicit knowledge for the AGL grammar (i.e., ability to freely generate grammatical strings) correlated positively with the variables of phonological processing and reading. Further, SRT reaction times correlated positively with full scale intelligence quotient (FIQ). We conclude that, in AGL, learning difficulties of the underlying rule structure (as measured by grammaticality) are associated with dyslexia and ADHD. However, learning in AGL is not related to the defining neuropsychological features of dyslexia or ADHD. Instead, the resulting explicit knowledge relates to characteristics of dyslexia.

Twin Research and Human Genetics, 2010

Psychological Science, 2010

Psychological Medicine, 1995

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2009

In project DyAdd, we compared the fatty acid (FA) profiles of serum phospholipids in adults with ... more In project DyAdd, we compared the fatty acid (FA) profiles of serum phospholipids in adults with attention deficit hyperactivity disorder (ADHD) (n=26), dyslexia (n=36), their comorbid combination (n=9), and healthy controls (n=36). FA proportions were analyzed in a 2x2 design with Bonferroni corrected post hoc comparisons. A questionnaire was used to assess dietary fat quality and use of supplements. Results showed that ADHD and dyslexia were not associated with total saturated FAs, monounsaturated FAs, or n-3 polyunsaturated FAs (PUFAs). However, those with ADHD had elevated proportions of total n-6 PUFAs (including gamma-linolenic and adrenic acids) as compared to those without ADHD. Dyslexia was related to a higher proportion of monounsaturated nervonic acid and a higher ratio of n-6/n-3 PUFAs. Among females none of the associations were significant. However in males, all the original associations observed in all subjects remained and ADHD was associated with elevated nervonic acid and n-6/n-3 PUFA ratio like dyslexia. Controlling for poorly diagnosed reading difficulties, education, dietary fat quality, or use of FA supplements did not generally remove the originally observed associations.

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2009

Both attention deficit hyperactivity disorder (ADHD) and dyslexia are suggested to co-occur with ... more Both attention deficit hyperactivity disorder (ADHD) and dyslexia are suggested to co-occur with altered fatty acid (FA) metabolism, but it is unknown how FAs are associated with the cognitive domains that characterize these disorders. In the project DyAdd, we investigated the associations between FAs in serum phospholipids and phonological processing, reading, spelling, arithmetic, executive functions, and attention. Healthy controls (n=36), adults with ADHD (n=26), dyslexia (n=36), or both (n=9) were included in the study. FAs included saturated, monounsaturated, total polyunsaturated, n-3, and n-6 FAs, together with n-6/n-3, AA/EPA, and LA/ALA ratios. When all the study subjects were included in the analyses, especially polyunsaturated FAs (PUFAs) were positively associated with cognition, but reading was least associated with FAs. These associations were modulated by gender, intelligence, n-3 PUFA intake, and group. Accordingly, within the ADHD group, only few associations emerged with PUFAs, n-6 PUFAs, and cognitive domains, whereas in the dyslexia group the more prevalent associations appeared with PUFAs and n-3 PUFAs.

Pharmacology Biochemistry and Behavior, 1994

The cognitive effects of high-dose human leukocyte alpha-interferon (IFN-alpha) treatment were ev... more The cognitive effects of high-dose human leukocyte alpha-interferon (IFN-alpha) treatment were evaluated among 15 patients with the newly diagnosed spinal form of amyotrophic lateral sclerosis (ALS). To confirm the earlier findings showing reversible effects on cognitive performance and to exclude confounding effects, a randomized blinded placebo controlled study was conducted. Twelve patients with continuous intravenous IFN-alpha-infusion treatment over five days and 3 placebo control patients were neuropsychologically evaluated. The neuropsychological examination included tests of intelligence, memory, complex mental processing, visuoconstructional skills, writing, and calculation. A clear difference in the performance profiles of the placebo and the IFN-alpha-treated patient groups was detected: The IFN-alpha group showed significant deterioration during treatment in the digit span backwards task, logical verbal memory task, calculation ability, and writing time, while improvement was seen after treatment. Concomitant fever did not explain the findings. In the placebo group an improvement indicating a learning effect in the three consecutive measurements was found. The reversible cognitive deterioration indicates a clear CNS effect during the IFN-alpha treatment.

Parkinsonism & Related Disorders, 2008

Cognitive dysfunction is common in Parkinson&amp;amp;#39;s disease (PD). Low plasma uric acid... more Cognitive dysfunction is common in Parkinson&amp;amp;#39;s disease (PD). Low plasma uric acid level is a risk factor for PD but its association with cognitive impairment in PD has not been previously studied. In the present study urine uric acid level as well as plasma uric acid- and homocysteine levels were measured in 40 patients with PD. Comprehensive neuropsychological tests including computerized tasks were performed on all. Both low plasma and low urine uric acid levels associated with decreased neuropsychological performance. In multiple linear regression low urine uric acid level predicted worse performance in the Picture completion subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (p=0.003) and in the Rule shift cards test of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) (p=0.04). Low plasma uric acid level predicted worse performance both in the Picture completion (p=0.02) and Similarities subtest of the WAIS-R (p=0.02). Reaction time and the time spent on cognitive processing in the Statement verification task were inversely correlated with the uric acid levels (p=0.0001). There was no correlation between the homocysteine level and neuropsychological performance. Instead, the plasma uric acid and homocysteine levels correlated significantly and their possible association in PD is discussed.