Timo Erkinjuntti

Haptoglobin (Hp) is a plasma protein that binds free hemoglobin and protects tissues from oxidative damage. An Hp2 allele has been associated with an increased risk of cardiovascular complications. On the other hand, recent studies have suggested that Hp1 allele increases risk to develop severe cerebral small vessel disease. We aimed to replicate this finding in a first-ever stroke patient cohort. Hp was genotyped by PCR and gel electrophoresis in the Helsinki Stroke Aging Memory Study in patients with DNA and magnetic resonance imaging (MRI) available (SAM; n = 316). Lacunar infarcts and white matter lesions (WML) classified by Fazekas grading from brain MRI were associated with Hp genotypes. As population controls, we used participants of Cardiovascular diseases—a sub study of Health 2000 Survey (n = 1417). In the SAM cohort, 63.0% of Hp1-1 carriers (n = 46), 52.5% of Hp1-2 carriers (n = 141) and 51.2% of Hp2-2 carriers (n = 129) had severe WML (p = 0.372). There was no difference in severe WMLs between Hp1-1 vs. Hp1-2 and Hp2-2 carriers (p = 0.201). In addition, 68.9% of Hp1-1 carriers (n = 45), 58.5% of Hp1-2 carriers (n = 135), and 61.8% of Hp2-2 carriers (n = 126) had one or more lacunar lesions (p = 0.472). There was no difference in the number of patients with at least one lacunar infarct between Hp1-1 vs. Hp1-2 and Hp2-2 groups (p = 0.322). Neither was there any difference when diabetic patients (type I and II) were examined separately. Hp1 allele is not associated with an increased risk for cerebral small vessel disease in a well-characterized Finnish stroke patient cohort.

Background and purpose: Cerebral small vessel disease (SVD) is characterized by a wide range of focal and global brain changes. We used automated MRI segmentation to quantify multiple types of SVD brain changes and examined their individual and combined predictive value on cognitive and functional abilities. Methods: MRI scans of 560 subjects of the Leukoaraiosis and Disability Study (LADIS) were analyzed using automated atlas- and convolutional neural network-based segmentation methods yielding volumetric measures of white matter hyperintensities (WMH), lacunes, cortical infarcts, enlarged perivascular spaces and regional brain atrophy. The subjects were followed up with annual neuropsychological examinations for 3 years and evaluation of instrumental activities of daily living for 7 years. Results: The strongest predictors of cognitive performance and functional outcome over time were total volumes of WMH, grey matter (GM) and hippocampi (p<0.001 for global cognitive function, processing speed, executive functions and memory; and p<0.001 for poor functional outcome). Volumes of lacunes, cortical infarcts and EVPS were significantly associated with part of the outcome measures, but their contribution was weaker. In a multivariable linear mixed model, volumes of WMH, lacunes, GM and hippocampi remained as independent predictors of cognitive impairment. A combined measure of these markers based on z-scores strongly predicted cognitive and functional outcomes (p<0.001) even above the contribution of the individual brain changes. Conclusions: Global burden of SVD-related brain changes as quantified by automated image segmentation is a powerful predictor of long-term cognitive decline and functional disability. A combined measure of WMH, lacunar, GM and hippocampal volumes could be used as an imaging identification model of vascular cognitive impairment.

Women die of stroke more often than men. After menopause, the incidence of ischemic stroke increases rapidly. Elevated fibrinogen levels and smoking have been associated with an increased risk of stroke. In gene-cluster haplotype analyses, the beta-fibrinogen (FGB) promoter −455 G/A polymorphic locus was most strongly associated with elevated plasma fibrinogen levels. We investigated whether the FGB −455 G/A polymorphism and smoking might interact with sex on longterm survival of acute stroke sufferers. The Stroke Aging Memory (SAM) cohort comprising 486 consecutive stroke patients (55–85 years, 246 men, 240 women) subjected to clinical and MRI examination was followed over 12.5 years. During this period 347 (71.4%) patients died. The genotypes of the FGB −455 G/A polymorphism were determined by PCR. The FGB −455 G/A polymorphism genotype distributions were 64.7%, 32.1%, and 3.2% for GG, GA, and AA, respectively. During the follow-up, the FGB −455 A + genotype did not associate with survival, nor was there any genotype-by-smoking interaction on poor outcome in the total study population. However, women aged 55–71 years who carried the FGB −455 A-allele showed worse survival regardless of smoking status compared to non-smoking FGB −455 GG homozygotes (non-smokers, crude HR = 5.21, 95% CI: 1.38-19.7; smokers, crude HR = 7.03, 95% CI: 1.81-27.3). This association persisted in adjusted analyses. No such association was observed for women in the oldest age-group, nor among men. The A + genotype of the FGB −455 G/A polymorphism associated with poor survival among 55–71 years old Caucasian women in the Finnish stroke cohort.

Indications for brain imaging include potentially treatable intracranial causes (e.g. normal-pressure hydrocephalus, tumors, subdural hematoma) and especially characteristic features of memory disorders and differential diagnostics of such conditions. Since the primary structural changes in the most common progressive memory disorder, Alzheimer's disease, are seen in the inner temporal lobe, appropriate imaging of these structures is essential in early diagnosis.

The evaluation of cognitive functions by using CERAD (Consortium to Establish a Registry for Alzheimer's Disease) is recommended as a tool in basic health care for screening of memory diseases. The reliability of this method, adopted in Finland in 1999, has been impaired by the fact that there have been no comprehensive Finnish norms to serve as the basis for the cut-off limits of the test tasks. This article presents the new, revised cut-off values for the CERAD procedure, based on the comparison of Finnish population-based normative data with those of persons having very mild or mild Alzheimer's disease.

Any complaints from a patient about their memory should be examined. Diagnosis is based on international criteria. The basic evaluation consists of the medical history, clinical evaluation, cognitive tests and brain imaging, especially using MRI. When a diagnosis of Alzheimer's disease, AD with cerebrovascular disease or with Lewy Body disease, or Dementia associated with Parkinson's disease or LBD is made, evidence based medical therapy is indicated as part of comprehensive care. An acetylcholinesterase inhibitor or memantine can be used. These drugs are ineffective in the case of frontotemporal degenerations. For severe behavioural disorders, other psychoactive medications can be applied.

Vascular cognitive impairment, the recent modification of the terminology related to vascular burden of the brain, reflects the all-encompassing effects of vascular disease or lesions on cognition. It incorporates the complex interactions between vascular aetiologies, risk factors and cellular changes within the brain and cognition. The concept covers the frequent poststroke cognitive impairment and dementia, as well as cerebrovascular disease (CVD) as the second most common factor related to dementia. CVD as well as vascular risk factors including arterial hypertension, history of high cholesterol, diabetes or forms of heart disease are independently associated with an increased risk of cognitive impairment and dementia. Traditional vascular risk factors and stroke are also independent factors for the clinical presentation of Alzheimer’s disease (AD). In addition to these vascular factors, CVD/strokes, infarcts and white-matter lesions may trigger and modify the progression of AD as the most common cause of neurodegenerative dementia. The main subtypes of previously defined vascular dementia (VaD) include the cortical VaD or multi-infarct dementia also referred as poststroke VaD, subcortical ischaemic vascular disease and dementia or small-vessel dementia and strategic-infarct dementia. Whilst CVD is preventable and treatable, it is clearly a major factor in the prevalence of cognitive impairment in the elderly worldwide.