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Contains fulltext : 305366.pdf (Publisher’s version ) (Open Access), BACKGROUND AND PURPOSE: Arterial calcifications on unenhanced CT scans and vessel wall lesions on MRI are often used interchangeably to portray intracranial arterial disease. However, the extent of pathology depicted with each technique is unclear. We investigated the presence and distribution of these two imaging findings in patients with a history of cerebrovascular disease. MATERIALS AND METHODS: We analyzed CT and MRI data from 78 patients admitted for stroke or TIA at our institution. Vessel wall lesions were assessed on 7 T MRI sequences, while arterial calcifications were assessed on CT scans. The number of vessel wall lesions, severity of intracranial internal carotid artery (iICA) calcifications, and overall presence and distribution of the two imaging findings were visually assessed in the intracranial arteries. RESULTS: At least one vessel wall lesion or arterial calcification was assessed in 69 (88%) patients. Only the iICA and vertebral arteries (VA) showed a substantial number of both calcifications and vessel wall lesions. The other vessels showed almost exclusively vessel wall lesions. The number of vessel wall lesions was associated with the severity of iICA calcification (p = 0.013). CONCLUSIONS: The number of vessel wall lesions increases with the severity of iICA calcifications. Nonetheless, the distribution of vessel wall lesions on MRI and arterial calcifications on CT shows remarkable differences. These findings support the need for a combined approach to examine intracranial arterial disease.

Background: Low birth weight is associated with an increased risk of adulthood cerebrovascular disease (CVD). Not much is known about effects of early childhood growth. We studied whether the risk of adult CVD is associated with growth or nutritional factors during early childhood. Methods: Within the Northern Finland Birth Cohort 1966, 11 991 persons were followed from birth to 52 years of age. CVD diagnoses were extracted from national hospital and death registers with diagnostic coding based on the World Health Organization recommendations. Cox proportional hazard models were used to estimate associations of childhood growth variables, growth trajectories (by Latent Class Growth Modeling), and nutritional factors with adult CVD, for example, ischemic and hemorrhagic strokes. The analyses were adjusted for childhood socioeconomic status and birth weight. Results: A total of 453 (3.8%) CVDs were recorded during follow-up. Among females, groups with low early childhood weight and height had an increased risk for adulthood ischemic CVDs, with an adjusted hazard ratio of 1.97 (95% CI, 1.21–3.20) and 2.05 (CI, 1.11–3.81), respectively. In addition, females with body mass index over 1 SD at body mass index rebound had an increased risk for ischemic CVDs (adjusted hazard ratio, 1.90 [CI, 1.19–3.04]) compared with females with body mass index −1 to +1 SD. These associations were not found among males. Conclusions: The findings suggest that timing of weight gain during childhood is of significance for development of CVD risk among females.

Background: Severe health events may lead to reduced income among survivors. Importantly, individuals’ risks for both severe health events and for lower income are shaped by early life course. Our aim was to consider early-life factors in determining lost individual income after stroke, heart attack and cancer between ages 18 and 50. Methods: A population-based Northern Finland Birth Cohort 1966 (N = 12 058) was used. Early-life factors were collected since mid-pregnancy until age 16 years and used to match all persons with stroke, heart attack, or cancer (n = 995) with four controls. Registered annual individual income development 15 years before and after the event was compared between cases and propensity score matched controls using time-to-event mixed models, stratified for sex. Results: Compared to controls, a new decreasing income trend emerged among women after stroke (logarithmic income per time −0.54; 95% CI −0.88 to −0.20), whereas men getting stroke showed declining earnings already by the time of the event, further declining after stroke (−1.00, −1.37 to −0.63). Getting heart attack was associated with a new declining trend both in women (−0.68; −1.28 to −0.09) and men (−0.69, −1.05 to −0.32). Income declined also among control men (−0.24, −0.34 to −0.14), who had higher income but were less educated than control women. Conclusions: Stroke and heart attack but not cancer have exogenous deleterious effects on individual economy, independently of early-life factors. The effects accelerate by time. Negative income trend in control men shows that severe health events do not explain all decrease in income.

Family’s socioeconomic profile collected prenatally is known to predict offspring mortality during early life, but it remains unclear whether it has the potential to predict offspring mortality until later life. In this study, 12,063 individuals belonging to the Northern Finland Birth Cohort 1966 were followed up from mid-pregnancy for 52 years (570,000 person years). Five distinct socioeconomic profiles were identified by latent class analysis based on mother’s marital status, education, and occupation; father’s occupation; number of family members; location of residence, room count, and utilities; and family’s wealth. The classes were highest status families (15.4% of the population), small families (22.1%), larger families (15.4%), average wealth families (23.4%), and rural families (23.3%). Their associations to offspring mortality, via linkage to national offspring death records, were analysed by Cox regression, stratified by sex and age groups (0—19, 20—38 and 40–52 years). In total, mortality was 9.2% among male and 5.0% among female offspring. Risk for midlife mortality was higher among male offspring from larger families (hazard ratio 2.19, 95% confidence interval 1.32—3.63), average wealth families (1.66, 1.02—2.73) and rural families (1.63, 1.00—2.68), relative to offspring from highest status families. It seems that family’s socioeconomic profile constructed prenatally has predictive value for midlife mortality among male offspring. Premature mortality of men and women seem to be two distinct phenomena with differing underlying factors as socioeconomic profile was not associated with mortality among female offspring.

The aim of this thesis was to explore associations between growth and development during childhood and risk of later stroke within the Northern Finland Birth Cohort 1966 (NFBC1966). Specifically, whether 1) pregnancy and birth related risk factors 2) height, weight, and BMI growth before school age or 3) childhood motor and language milestone achievement are associated with increased stroke risk in adulthood. The NFBC1966 is a population-based birth cohort consisting of 12,068 pregnant women and their 12,058 live-born children. This dissertation utilizes data that has been collected from medical records, national registers, clinical examinations, and questionnaires and a follow-up of up to 54 years. The results show that several early life factors are associated with increased risk of young adult strokes. A novel finding is the association of low maternal weight gain and offspring’s risk of ischemic stroke, which was independent of birth weight. Low weight, height and ponderal index at time of birth were markers of increased stroke risk in later life. Among girls also below average weight or height growth during the first 2 years of life and above average BMI before school age associated with adulthood stroke risk. In addition, the results suggest childhood developmental milestone achievement has predictive value for later life strokes. This study is one of the few to investigate early life factors in relation to adulthood stroke. The results of this thesis support the notion that early development, beginning during prenatal stages, can provide useful indicators of future processes influencing stroke risk., Tiivistelmä Tämän väitöskirjatutkimuksen tarkoituksena oli tutkia lapsuusajan kasvun ja kehityksen yhteyttä aikuisiän aivoverenkiertohäiriöriskiin vuoden 1966 Pohjois-Suomen syntymäkohortissa (NFBC1966). Tarkemmin eriteltynä, oliko 1) raskauden ja synnytyksen aikaisillä riskitekijöillä, 2) pituus-, paino- ja painoindeksikasvulla ennen kouluikää tai 3) lapsuuden motorisella tai kielellisellä kehityksellä yhteyttä lisääntyneeseen aivoverenkiertohäiriöön aikuisiällä. Pohjois-Suomen vuoden 1966 syntymäkohortti on valikoitumaton, yleisväestöpohjainen kohortti, joka sisältää tiedot 12068 raskaana olevasta naisesta ja heidän 12058 elävänä syntyneestä lapsestaan. Tässä väitöskirjatutkimuksessa hyödynnetiin tietoja sairauskertomuksista, kansallisista rekistereistä, kliinisistä tutkimuksista ja kyselyistä 54 vuoden seuranta-aikana. Tutkimuksen tulokset osoittivat, että useilla varhaiskehityksellisillä tekijöillä on yhteyttä lisääntyneeseen riskiin sairastua aivoverenkiertohäiriöön nuorena aikuisena. Uutena havaintona osoitettiin yhteys äidin raskaudenaikaisen vähäisen sekä suuren painonnousun ja lapsen kohonneen aivoverenkiertohäiriöriskin välillä. Yhteys oli riippumaton syntymäpainosta. Pieni paino, pituus ja ponderaali-indeksi syntymähetkellä ennustivat suurentunutta aikuisiän aivoverenkiertohäiriöriskiä. Naisilla myös keskimääräistä pienempi paino- tai pituuskasvu ensimmäisten 2 elinvuoden aikana ja keskimääräistä suurempi painoindeksi ennen kouluikää olivat yhteydessä myöhempään aivoverenkiertohäiriöriskiin. Lisäksi myös lapsuuden motorisella ja kielellisellä kehityksellä osoitettiin olevan ennustearvoa nuorten aikuisten aivoverenkiertohäiriöille. Tämä väitöskirjatutkimus on yksi harvoista, joissa tutkitaan varhaiskehityksen yhteyttä aikuisiän aivoverenkiertohäiriöriskiin. Tutkimuksen tulokset tukevat käsitystä, että varhaiskehitys, alkaen sikiökehityksestä, voi tarjota hyödyllisiä indikaattoreita tulevaisuuden aivoverenkiertohäiriöriskin kehittymiselle.

Background and purpose: For prevention of cerebrovascular diseases at younger age, it is important to understand the risk factors occurring early in life. We investigated the relationship between mothers’ general health during pregnancy and the offspring’s risk of cerebrovascular disease in age of 15 to 52 years. Methods: Within the population-based prospective Northern Finland Birth Cohort 1966, 11,926 persons were followed from antenatal period to 52 years of age. Information on their mother’s ill health conditions, i.e., hospitalizations, chronic diseases, medications, vitamin or iron supplement, fever, anemia, mood, and smoking was collected from 24th gestational week onwards. Ischemic and hemorrhagic cerebrovascular diseases of the offspring were identified from national registers in Finland. Cox proportional hazard models were used to estimate the association of mother’s health conditions with incidence of cerebrovascular disease in the offspring, with adjustments for potential confounders. Results: During 565,585 person-years of follow-up, 449 (2.8%) of the offspring had a cerebrovascular disease. Hospitalization during pregnancy was associated with an increased risk of cerebrovascular disease in the offspring (hazard ratio (HR) = 1.49; 95% confidence interval (CI) 1.06–2.08) after adjustment for confounders, as was having more than three ill health conditions (HR = 1.89; CI 1.14–3.11). Not using vitamin or iron supplement was associated with increased risk for cerebrovascular disease in the offspring (HR = 1.39; CI 1.01–1.89). Conclusions: The results suggest that the risk of cerebrovascular disease may start as early as during the antenatal period, and the health characteristics of mothers during pregnancy may play a role in cerebrovascular disease risk of the offspring.

Smoking remains among the leading causes of mortality worldwide. Obtaining a comprehensive understanding of a population’s smoking behaviour is essential for tobacco control. Here, we aim to characterize lifelong smoking patterns and explore underlying sociodemographic and lifestyle factors in a population-based birth cohort population followed up for 46 years. Our analysis is based on 5797 individuals from the Northern Finland Birth Cohort 1966 who self-reported their tobacco smoking behaviour at the ages of 14, 31 and 46. Data on sex, education, employment, body mass index, physical activity, alcohol consumption, and substance addiction were also collected at the follow-ups. We profile each individual’s annual smoking history from the age of 5 to 47, and conduct a latent class trajectory analysis on the data. We then characterize the identified smoking trajectory classes in terms of the background variables, and compare the heaviest smokers with other classes in order to reveal specific predictors of non-smoking and discontinued smoking. Six smoking trajectories are identified in our sample: never-smokers (class size 41.0%), youth smokers (12.6%), young adult quitters (10.8%), late adult quitters (10.5%), late starters (4.3%), and lifetime smokers (20.7%). Smoking is generally associated with male sex, lower socioeconomic status and unhealthier lifestyle. Multivariable between-class comparisons identify unemployment (odds ratio [OR] 1.28–1.45) and physical inactivity (OR 1.20–1.52) as significant predictors of lifetime smoking relative to any other class. Female sex increases the odds of never-smoking and youth smoking (OR 1.29–1.33), and male sex increases the odds of adult quitting (OR 1.30–1.41), relative to lifetime smoking. We expect future initiatives to benefit from our data by exploiting the identified predictors as direct targets of intervention, or as a means of identifying individuals who may benefit from such interventions.

The aim of this thesis was to explore the associations between the use of nervous system medications and suicidal ideation and behaviour in various different diagnostic groups in a large population-based cohort. Information on prescribed antipsychotic, antidepressant, benzodiazepine and antiepileptic medications within the Northern Finland Birth Cohort 1966 was collected from the register of the Social Insurance Institution of Finland and from a postal questionnaire sent to all cohort members in 1997. The presence of suicidal ideation and depression and anxiety symptoms was assessed via the Hopkins Symptom Checklist-25 questionnaire in 1997. Data on suicides were collected from the cause-of-death statistics and on suicide attempts from the Finnish Care Register for Health Care in a 15-year follow up. The use of antipsychotic, antidepressant, or benzodiazepine medication was associated with increased suicidal ideation, suicide attempts, and suicides. Antiepileptic medication was not associated with increased suicidality. The polypharmacy of nervous system medications was associated with increased suicidality. All nervous system medications were associated with increased severity of depression and anxiety symptoms. When depression and anxiety symptoms were taken into account, most of the associations between medication and suicidal ideation were statistically non-significant. Regarding specific groups, among those who did not have psychosis, high doses of antipsychotic medication correlated particularly with increased suicidal ideation even when other symptoms of depression and anxiety were taken into account. Among those with insomnia, the use of antidepressant medication associated with increased suicidal ideation also when other symptoms were taken into account. Although nervous system medication is associated with increased suicidal ideation, the association with other symptoms is also strong, and therefore it could not be stated that medication associate, Tiivistelmä Tämän väitöstutkimuksen tarkoituksena oli tutkia hermostoon vaikuttavien lääkkeiden, lähinnä psykoosilääkkeiden, masennuslääkkeiden, bentsodiatsepiinien sekä epilepsialääkkeiden, yhteyttä itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Aihetta tutkittiin eri diagnoosiluokissa suuressa väestöaineistossa, Pohjois-Suomen vuoden 1966 syntymäkohortissa. Tieto tutkimushenkilöiden lääkkeenkäytöstä vuodelta 1997 kerättiin Kelan lääkeostorekisteristä sekä postikyselyn avulla. Itsetuhoisten ajatusten ja muiden masennus- ja ahdistusoireiden vakavuutta mitattiin Hopkins Symptom Checklist-25 -kyselyn avulla vuonna 1997. Tieto itsemurhista kerättiin 15 vuoden seurannassa kuolinsyyrekisteristä ja tieto itsemurhayrityksistä hoitoilmoitusrekisteristä. Psykoosilääkkeiden, masennuslääkkeiden ja bentsodiatsepiinien käyttö oli yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, itsemurhayrityksiin ja itsemurhiin. Epilepsialääkkeet eivät liittyneet itsetuhoisuuteen. Usean hermostoon vaikuttavan lääkkeen yhtäaikainen käyttö oli yhteydessä lisääntyneeseen itsetuhoisuuteen. Kaikki hermostoon vaikuttavat lääkkeet liittyivät lisääntyneisiin masennus- ja ahdistusoireisiin. Kun lääkityksen yhteys masennus- ja ahdistusoireisiin otettiin huomioon, lääkkeet eivät olleet erityisesti yhteydessä itsetuhoisiin ajatuksiin. Diagnostisten ryhmien välillä ei ollut eroa hermostoon vaikuttavien lääkkeiden ja itsemurhayritysten tai itsemurhien välisessä yhteydessä. Henkilöillä, joilla ei ole psykoosia, suuremmat psykoosilääkeannokset olivat yhteydessä itsetuhoisten ajatusten vakavuuteen kun muiden masennus- ja ahdistusoireiden vakavuus otettiin huomioon. Unettomuudesta kärsivillä henkilöillä masennuslääkkeen käyttö oli liittyi lisääntyneisiin itsetuhoisiin ajatuksiin kun muut oireet huomioitiin. Hermostoon vaikuttavat lääkkeet ovat yhteydessä lisääntyneisiin itsetuhoisiin ajatuksiin, mutta ne ovat myös vahvasti yhteydessä muihin masennus- ja ahdistusoireisiin. Tietyt henkilöt voiva