In the spotlight: Bioinstrumentation

金沢大学理工研究域機械工学

Measures of onset, progression and intervention in Alzheimer’s disease: the familial paradigm

Familial Alzheimer’s disease (FAD) is a valuable paradigm for the study of the more common sporadic AD (SAD). The two forms of the illness share many neuropathological, clinical and radiological characteristics but it is not yet possible to predict the onset of SAD or confirm its presence without histopathological analysis. Fully penetrant amyloid precursor protein (APP), presenilin 1 (PSEN1) or presenilin 2 (PSEN2) gene mutations permit both, and therefore lend themselves to clinical research with results which may be applied to the study of SAD. The identification of biomarkers of onset and progression are vital in the selection of research participants and in the rapid evaluation of new therapies. This thesis further characterizes FAD with a number of studies. These address the use of imaging biomarkers and help clarify the nature of the relationship between FAD and SAD. Two reports of novel pathogenic FAD mutations are included as well as other studies exploring the clinical and radiological (structural and molecular) phenotypes associated with FAD. Key findings are as follows: the novel PSEN1 p. L166del and S132A mutations are both associated with FAD; the APPV717G mutation can be associated with pure progressive amnesia reflected in an atypical structural imaging profile; APP locus duplication is a significant cause of early onset dementia in the UK and the recognised phenotype should be expanded to include early seizures and apparently sporadic disease; regional cortical thickness (CTh) decline accelerates after diagnosis in FAD mutation carriers (MC) and differences between MC and controls are detectable in presymptomatic mutation carriers more than 4 years prior to clinical diagnosis; APP and PSEN1 mutations may produce different temporal and topographical patterns of cortical change; increased 11C-PiB retention in a highly heterogeneous pattern may be detected in presymptomatic PSEN1 mutation carriers

Early detection of Alzheimer’s disease - Twin study on episodic memory and imaging biomarkers of neuroinflammation and β-amyloid

The disease process of Alzheimer’s disease (AD) causes damage to the brain for several years leading to the development of mild cognitive impairment (MCI) and finally to dementia which interferes with independent living. The early detection of AD disease process is key for the prevention and treatment of disease. The aim of this thesis was to improve the assessment of episodic memory (EM) and cognitive performance with a telephone interview and neuroimaging of early AD. The study population belonged to the older Finnish Twin Cohort study. 2631 twins (856 pairs) participated in the telephone interview (TELE, TICS) during 1999–2007 and 1817 twins (559 pairs) participated in the interview (TELE, TICS, TICS-m) during 2013– 2017. Cognitively discordant twin pairs were asked to participate in more detailed examinations. 11 twin pairs participated in [11C]PBR28 positron emission tomography (PET) imaging measuring neuroinflammation during 2014–2017 and 45 twin pairs participated in [11C]PiB PET imaging measuring β-amyloid (Aβ) deposits during 2005–2017. Twins who had co-twins with dementia (n=101) performed poorer than average in a word list learning test. When using the telephone interview TICS-m, the education‐adjusted classification resulted in a higher proportion of apolipoprotein (APOE) ε4 allele carriers among those identified as having MCI. Twins with poorer EM performance (n=10) had higher cortical [11C]PBR28 uptake compared to their better-performing co-twins. In addition, higher cortical [11C]PiB uptake was associated with poorer EM performance. The results from the telephone interview studies indicate that poorer word list learning performance may be an early marker of dementia risk and that the use of education‐adjustment may increase the accuracy of MCI classification. The twin pair setting controlling for genetic and environmental effects indicated that brain Aβ load and neuroinflammation have a negative association with EM performance.Alzheimerin taudin varhainen havaitseminen – Kaksostutkimus episodisesta muistista ja neuroinflammaation ja β-amyloidin kuvantamisbiomarkkereista Alzheimerin taudin (AT) prosessi vaurioittaa aivoja vuosien ajan ja johtaa lievään kognitiiviseen heikentymiseen (MCI) ja lopulta itsenäistä selviytymistä häiritsevään dementiaan. AT:n dementiaan johtavan prosessin varhainen havaitseminen on avainasemassa ehkäisyn ja hoidon kannalta. Tämän väitöskirjatutkimuksen tavoitteena oli kehittää puhelinhaastattelun käyttöä episodisen muistin (EM) ja muiden tiedonkäsittely- eli kognitiivisten toimintojen arvioimisessa sekä AT:n varhaista kuvantamista. Tutkimusjoukko kuului vanhempaan suomalaisen kaksoskohorttitutkimukseen. 2631 kaksosta (856 paria) osallistui puhelinhaastatteluun (TELE, TICS) 1999–2007 aikana ja 1817 kaksosta (559 paria) osallistui haastatteluun (TELE, TICS, TICS-m) 2013–2017 aikana. Kognitiivisesti diskordantit kaksosparit kutsuttiin tarkempiin jatkotutkimuksiin. 11 kaksosparia osallistui neuroinflammaatiota mittaavaan [11C]PBR28-merkkiaineen positroniemissiotomografia (PET) - kuvaukseen 2014–2017 aikana ja 45 kaksosparia osallistui aivojen β-amyloidikertymää mittaavaan [11C]PiB-merkkiaineen PET-kuvaukseen 2005–2017 aikana. Sellaisten kognitiivisesti normaalien ikääntyneiden kaksosten (n=101), joiden sisaruksella oli dementia, havaittiin suoriutuvan keskimääräistä heikommin sanalistan oppimista mittaavassa testissä. Käytettäessä TICS-m-puhelinhaastattelua koulutuskorjauksen käyttäminen johti siihen, että MCI:tä sairastavien joukossa oli suurempi osuus apolipoproteiini E:n (APOE) ε4-alleelin kantajia. Kaksosilla (n=10), jotka suoriutuivat heikommin EM-testeissä, oli suurempi aivokuoren [11C]PBR28-kertymä verrattuna paremmin suoriutuviin sisaruksiinsa. Myös suurempi aivokuoren [11C]PiB-kertymä oli yhteydessä heikompaan EM-suoritukseen. Puhelinhaastattelujen tulokset viittaavat siihen, että sanalistan oppiminen voi olla dementiariskistä kertova varhainen merkki ja että koulutuskorjauksen käyttö voi lisätä MCI-luokittelun tarkkuutta. Kaksosasetelma, joka kontrolloi geneettisten ja ympäristötekijöiden vaikutusta, osoitti, että aivojen β-amyloidikertymä ja neuroinflammaatio ovat negatiivisessa yhteydessä EM:n toiminnan kanssa

What makes us tic?

Published work 1971-2006, comprising 4 books, various articles, 2 review discussions on a videorecording, and supporting documents

Pilot study for subgroup classification for autism spectrum disorder based on dysmorphology and physical measurements in Chinese children

Poster Sessions: 157 - Comorbid Medical Conditions: abstract 157.058 58BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder affecting individuals along a continuum of severity in communication, social interaction and behaviour. The impact of ASD significantly varies amongst individuals, and the cause of ASD can originate broadly between genetic and environmental factors. Objectives: Previous ASD researches indicate that early identification combined with a targeted treatment plan involving behavioural interventions and multidisciplinary therapies can provide substantial improvement for ASD patients. Currently there is no cure for ASD, and the clinical variability and uncertainty of the disorder still remains. Hence, the search to unravel heterogeneity within ASD by subgroup classification may provide clinicians with a better understanding of ASD and to work towards a more definitive course of action. METHODS: In this study, a norm of physical measurements including height, weight, head circumference, ear length, outer and inner canthi, interpupillary distance, philtrum, hand and foot length was collected from 658 Typical Developing (TD) Chinese children aged 1 to 7 years (mean age of 4.19 years). The norm collected was compared against 80 ASD Chinese children aged 1 to 12 years (mean age of 4.36 years). We then further attempted to find subgroups within ASD based on identifying physical abnormalities; individuals were classified as (non) dysmorphic with the Autism Dysmorphology Measure (ADM) from physical examinations of 12 body regions. RESULTS: Our results show that there were significant differences between ASD and TD children for measurements in: head circumference (p=0.009), outer (p=0.021) and inner (p=0.021) canthus, philtrum length (p=0.003), right (p=0.023) and left (p=0.20) foot length. Within the 80 ASD patients, 37(46%) were classified as dysmorphic (p=0.00). CONCLUSIONS: This study attempts to identify subgroups within ASD based on physical measurements and dysmorphology examinations. The information from this study seeks to benefit ASD community by identifying possible subtypes of ASD in Chinese population; in seek for a more definitive diagnosis, referral and treatment plan.published_or_final_versio

Effects of Diversity and Neuropsychological Performance in an NFL Cohort

Objective: The aim of this study was to examine the effect of ethnicity on neuropsychological test performance by comparing scores of white and black former NFL athletes on each subtest of the WMS. Participants and Methods: Data was derived from a de-identified database in South Florida consisting of 63 former NFL white (n=28, 44.4%) and black (n=35, 55.6%) athletes (Mage= 50.38; SD= 11.57). Participants completed the following subtests of the WMS: Logical Memory I and II, Verbal Paired Associates I and II, and Visual Reproduction I and II. Results: A One-Way ANOVA yielded significant effect between ethnicity and performance on several subtests from the WMS-IV. Black athletes had significantly lower scores compared to white athletes on Logical Memory II: F(1,61) = 4.667, p= .035, Verbal Paired Associates I: F(1,61) = 4.536, p = .037, Verbal Paired Associates: II F(1,61) = 4.677, p = .034, and Visual Reproduction I: F(1,61) = 6.562, p = .013. Conclusions: Results suggest significant differences exist between white and black athletes on neuropsychological test performance, necessitating the need for proper normative samples for each ethnic group. It is possible the differences found can be explained by the psychometric properties of the assessment and possibility of a non-representative sample for minorities, or simply individual differences. Previous literature has found white individuals to outperform African-Americans on verbal and non-verbal cognitive tasks after controlling for socioeconomic and other demographic variables (Manly & Jacobs, 2002). This highlights the need for future investigators to identify cultural factors and evaluate how ethnicity specifically plays a role on neuropsychological test performance. Notably, differences between ethnic groups can have significant implications when evaluating a sample of former athletes for cognitive impairment, as these results suggest retired NFL minorities may be more impaired compared to retired NFL white athletes

Distinguishing Performance on Tests of Executive Functions Between Those with Depression and Anxiety

Objective: To see if there are differences in executive functions between those diagnosed with Major Depressive Disorder (MDD) and those with Generalized Anxiety Disorder (GAD).Participants and Methods: The data were chosen from a de-identified database at a neuropsychological clinic in South Florida. The sample used was adults diagnosed with MDD (n=75) and GAD (n=71) and who had taken the Halstead Category Test, Trail Making Test, Stroop Test, and the Wisconsin Card Sorting Test. Age (M=32.97, SD=11.75), gender (56.7% female), and race (52.7% White) did not differ between groups. IQ did not differ but education did (MDD=13.41 years, SD=2.45; GAD=15.11 years, SD=2.40), so it was ran as a covariate in the analyses. Six ANCOVAs were run separately with diagnosis being held as the fixed factor and executive function test scores held as dependent variables. Results: The MDD group only performed worse on the Category Test than the GAD group ([1,132]=4.022, p\u3c .05). Even though both WCST scores used were significantly different between the two groups, both analyses failed Levene’s test of Equality of Error Variances, so the data were not interpreted. Conclusions: Due to previous findings that those diagnosed with MDD perform worse on tests of executive function than normal controls (Veiel, 1997), this study wanted to compare executive function performance between those diagnosed with MDD and those with another common psychological disorder. The fact that these two groups only differed on the Category Test shows that there may not be much of a difference in executive function deficits between those with MDD and GAD. That being said, not being able to interpret the scores on the WCST test due to a lack of homogeneity of variance indicates that a larger sample size is needed to compare these two types of patients, as significant differences may be found. The results of this specific study, however, could mean that the Category Test could be used in assisting the diagnosis of a MDD patient

The Effect of Ethnicity on Neuropsychological Test Performance of Former NFL Athletes

Objective: To investigate the effect of ethnicity on neuropsychological test performance by specifically exploring differences between white and black former NFL athletes on subtests of the WAIS-IV. Participants and Methods: Data was derived from a de-identified database in Florida consisting of 63 former NFL athletes (Mage=50.38; SD=11.57); 28 white and 35 black. Participants completed the following subtests of the WAIS-IV: Block Design, Similarities, Digit Span, Matrix Reasoning, Arithmetic, Symbol Search, Visual Puzzles, Coding, and Cancellation. Results: One-Way ANOVA yielded a significant effect between ethnicity and performance on several subtests. Black athletes had significantly lower scaled scores than white athletes on Block Design F(1,61)=14.266, p\u3c.001, Similarities F(1,61)=5.904, p=.018, Digit Span F(1,61)=8.985, p=.004, Arithmetic F(1,61)=16.07, p\u3c.001 and Visual Puzzles F(1,61)=16.682, p\u3c .001. No effect of ethnicity was seen on performance of Matrix Reasoning F(1,61)=2.937, p=.092, Symbol Search F(1,61)=3.619, p=.062, Coding F(1,61)=3.032, p=.087 or Cancellation F(1,61)=2.289, p=.136. Conclusions: Results reveal significant differences between white and black athletes on all subtests of the WAIS-IV but those from the Processing Speed Scale and Matrix Reasoning. These findings align with previous literature that found white individuals to outperform African-Americans on verbal and non-verbal tasks after controlling for socioeconomic and demographic variables (Manly & Jacobs, 2002). These differences may also be a reflection of the WAIS-IV’s psychometric properties and it is significant to consider the normative sample used may not be appropriate for African-Americans. This study highlights the need for future research to identify how ethnicity specifically influences performance, sheds light on the importance of considering cultural factors when interpreting test results, and serves as a call to action to further understand how and why minorities may not be accurately represented in neuropsychological testing