Krister Håkansson

Observations on the functional significance of regional cerebral blood flow in "resting" normal subjects.

Abstract Regional Cerebral Blood Flow (rCBF) of 16 cortical regions was measured bilaterally in 22 healthy adults, with 4–8 repeated measurements per individual. All measurements were done during “rest”, i.e. with minimal external stimulation, by the Xe-133 inhalation method. The data are presented to serve as normal controls for research and clinical work, but more importantly because of their significance for neuropsychological theory. Some rCBF variance is shown to be meaningfully related to handedness, habituation processes, biological rhythms and possibly to regional lateral dominance. Further data and discussion relate to the possible role of frontal lobe structures during non-task-oriented cognition. Finally, data are interpreted as showing that regional functional coupling across the midline, in this situation, is inversely related to the characteristic level-of-processing associated with each area.

Regional blood flow changes in the left cerebral hemisphere during word pair learning and recall

Abstract Regional cerebral blood flow measurements were made in the left hemisphere of 11 young healthy volunteers during learning and during recalling of word pair associates. Compared to the resting baseline, both tasks caused significant increases of average hemispheric flow, indicating an elevated neuronal activity level. Regionally both tasks were accompanied by considerable activation of parietal and occipital regions. The main difference between learning and recalling was that only the former task activated the prefrontal regions.

Marital Status and Cognitive Impairment among Community-Dwelling Chinese Older Adults: The Role of Gender and Social Engagement

Aims: To examine the association between marital status and cognitive impairment among community-dwelling Chinese older adults. Methods: We analyzed data from 2,498 Chinese aged 55 and older from the Singapore Longitudinal Aging Study cohort. Cognitive impairment was defined as a Mini-Mental State Examination total score of 23 or below. Odds ratios of associations were reported and adjusted for potential confounders in logistic regression models. Results: The prevalence of cognitive impairment was 12.2% (n = 306). Being single was associated with about 2.5 times increased odds of cognitive impairment compared to being married (adjusted OR = 2.53, 95% CI: 1.41-4.55). The association between marital status and cognitive impairment was much stronger in men compared to that in women, and was indeed statistically significant only for men. Among the single and widowed persons social engagement was associated with a lower risk of cognitive impairment. Compared with subjects in the lowest tertile of social engagement scores, the odds of having cognitive impairment was lowered by 50% for subjects in the second and the third tertile. Conclusion: Being single or widowed was associated with higher odds of cognitive impairment compared to being married in a cohort of older Chinese men but not women.

Midlife Work-Related Stress Increases Dementia Risk in Later Life: The CAIDE 30-Year Study

Objective To investigate the associations between midlife work-related stress and mild cognitive impairment (MCI), dementia, and Alzheimers disease later in life, in a large representative population. Method Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study participants were randomly selected from independent population-based surveys (mean age 50 years). A random sample of 2,000 individuals was invited for two reexaminations including cognitive tests (at mean age 71 and mean age 78), and 1,511 subjects participated in at least one reexamination (mean follow-up 28.5 years). Work-related stress was measured using two questions on work demands that were administered in midlife. Analyses adjusted for important confounders. Results Higher levels of midlife work-related stress were associated with higher risk of MCI (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.08-1.76), dementia (OR, 1.53; CI, 1.13-2.07), and Alzheimers disease (OR, 1.55; CI, 1.19-2.36) at the first follow-up among the CAIDE participants. Results remained significant after adjusting for several possible confounders. Work-related stress was not associated with MCI and dementia during the extended follow-up. Discussion Midlife work-related stress increases the risk for MCI, dementia, and Alzheimers disease in later life. The association was not seen after the extended follow-up possibly reflecting selective survival/participation, heterogeneity in dementia among the oldest old, and a critical time window for the effects of midlife stress.

Feelings of Hopelessness in Midlife and Cognitive Health in Later Life: A Prospective Population-Based Cohort Study

Background Several studies have found depression and depressive feelings to be associated with subsequent dementia. As dementias typically have a long preclinical development phase, it has been difficult to determine whether depression and depressive feelings reflect a concurrent underlying dementia disease, rather than playing a causative role. Our aim was to investigate hopelessness, one dimension of depressive feelings, and evaluate the likelihood of a prodromal versus a causative role of hopelessness feelings in dementia development. Methods We invited a random sample of 2000 survivors from a representative population in Eastern Finland, originally investigated in midlife between 1972 and 1987, for re-examination an average of 21 years later. The age of the 1449 persons who accepted the invitation was between 39 and 64 years (mean 50.4 years) in midlife and between 65 and 80 (mean 71.3) at follow-up. To measure feelings of hopelessness in midlife and at follow-up, the participants indicated their level of agreement to two statements about their own possible future. We used logistic regression to investigate the association between the combined scores from these two items and cognitive health at follow-up, while adjusting for several health and life-style variables from midlife and for apolipoprotein E4 (ApoE4) status, depression and hopelessness feelings at follow-up. We compared the associations with late-life cognitive health when feelings of hopelessness were either measured in midlife or at the follow-up. In addition we analyzed the changes in hopelessness scores from midlife to follow-up in participants who were either cognitively healthy or impaired at follow-up. Results We found higher levels of hopelessness in midlife, but not at follow-up, to be associated with cognitive impairment at follow-up; the adjusted odds ratio for each step of the five-level hopelessness scale was 1.30 (95% confidence interval 1.11–1.51) for any cognitive impairment and 1.37 (1.05–1.78) for Alzheimer’s disease. These associations remained significant also after the final adjustments for depressive feelings and for hopelessness at follow-up. The individual changes in hopelessness scores between midlife and follow-up were not systematically related to cognitive health at the follow-up. Conclusion Our results suggest that feelings of hopelessness already in midlife may have long-term implications for cognitive health and increase the risk of Alzheimer’s disease in later life.

A Rare Success against Alzheimer's

Two hundred experimental drugs intended to treat Alzheimers disease have failed in the past 30 years. Without new therapies, the number of patients worldwide will increase dramatically by 2050.A r ...

Mid-life work-related stress increases dementia risk in late-life: The caide 30-year study

Background: The associations between work-related stress and various health outcomes in mid-life are well documented, yet less is known about the effects on late-life cognitive process and dementia. The current study investigated the associations between work-related stress in mid-life and the development of cognitive impairment and Alzheimer’s disease in late-life. Methods: The data was derived from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) study; a prospective cohort study. Participants were randomly selected from four independent population-based samples that completed cardiovascular surveys. First baseline examinations occurred when participants were 50 years old on average, in 1972, 1977, 1982, or 1987. A random sample of 2,000 individ- uals was selected for re-examinations (carried out in 1998 and 2005-2008), where 1,511 subjects participated in at least one re-examination. The re- examinations included an extensive neuropsychological and cognitive assessment. Follow-up time was on average 28 (S.E.M. 1⁄4 0.17) years. Work-related stress comprised the total score of two questions adminis- tered in mid-life. The questions asked participants to rate their stress related to meeting demands at work, and constant hurry at work. Groups were categorized so that those with high or medium levels of stress were compared to those with low levels or no work-related stress. Results: High levels of work-related stress in mid-life were associated with higherrisk of cognitive impairment (where participants with cognitive impair- ment and dementia were compared to the group with no cognitive impair- ment) [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.1], and Alzheimer’s disease [OR, 2.1; CI, 1.1-3.9], when assessed at the first or second follow-up. Results remained significant after adjusting for age, ed- ucation, marital status, chronic health conditions, apolipoprotein E e 4 allele (APOE e 4), measures of hopelessness and loneliness. Conclusions: High levels of mid-life work-related stress predict the risk of developing dementia in late-life. The evidence suggests that individuals experiencing high levels of work-related stress form an important at-risk population. Preventive interventions are needed for this population in order to post- pone or prevent the development of cognitive impairment and Alzheimer’s disease.

Cons and Pros of Epidemiological Versus Experimental Approaches to Answer Questions About Risk and Protective Factors for Alzheimer’s Disease: A Personal Journey

This text is a personal account of the research process that led to a dissertation about the long-term relevance of social and emotional factors for cognitive health. It describes how research idea ...

THE FEASIBILITY OF A HOME-BASED, SUBJECT-CONTROLLED, INTERACTIVE PHYSICAL EXERCISE PROGRAM TO PROMOTE COGNITIVE HEALTH IN OLDER ADULTS

Background:Increased physical activity (PA) is associated with better cognitive function. We investigated whether individuals with memory problems and additional cerebrovascular risk factors (CVD) could increase PA in the short-term and maintain adherence to a PA program in the long-term. We also examined factors influencing PA adherence.Methods:The AIBLActive trial recruited participants with mild cognitive impairment (MCI) or subjective memory complaints (SMC) and at least 1 CVD risk factor from The Australian Imaging Biomarkers and Lifestyle Flagship Study of Aging (AIBL). They were randomly assigned to a control or PA group. The control group continued their usual PA throughout the study. The PA group was given a 24-month home-based program with a target of 150 minutes/week of moderate PA and a behavioral intervention. Scheduled group-specific phone calls (n1⁄418) and newsletters (n1⁄417) were administered to both groups over 24 months. The PA group recorded sessions in diaries and adherence was calculated from the number of sessions recorded expressed as the percentage of the sessions prescribed. At baseline, 6, 12 and 24 months participants completed fitness (6-minute walk distance); PA and PA self-efficacy (one’s confidence to be physically active) questionnaires; cognitive and health assessments. Results:The adherence results for the PA group (n1⁄455) comprising of 53% women are reported. At baseline 24% were defined as inactive; men were significantly older than women; 74.7(6SD 5.6) versus 70.1(4.8) years respectively. Five participants did not start the intervention. After 24 months 96% were still in the study. After 6 months mean PA adherence was 83.5% and declined over the trial with mean 24-month adherence being 75.2%. Age, gender andMCI did not significantly influence adherence. Higher baseline self-efficacy (p<0.05) was associated with higher adherence in the first 6months with higher baseline self-efficacy (p<0.05) and fitness (p<0.01) associated with higher 24-month adherence. Positive program enjoyment, helpfulness of the telephone calls and newsletters were reported by 94%; 98% and 93% of participants respectively. Conclusions:The high retention and adherence rates in both the short and long-term demonstrate that this PA program was both achievable and acceptable in this target group.

Midlife hopelessness and white matter lesions two decades later: A population-based study

Background: Hopelessness has been associated with increased cardiovas- cular disease mortality and morbidity, subclinical atherosclerosis and meta- bolic syndrome. This study investigates the relation between midlife hopelessness and white matter lesions (WMLs) 20 years later in a Finnish population of men and women. Methods: Participants of the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study in Finland were derived from random, population-based samples previously surveyed in 1972,1977, 1982 or 1987. In 1998, 1449 (73%) individuals aged 65-79 years participated in the re-examination. A subgroup (n1⁄4112, including 39 dementia cases, 31 mild cognitive impairment (MCI) cases and 42 con- trols) underwent 1.5T MRI scanning at re-examination, and WMLs were as- sessed from FLAIR-images using a semi-quantitative visual rating scale. Hopelessness was measured by 2 questionnaire items (expectations about future and reaching goals). Results: Subjects with increased hopelessness had a significantly higher risk of developing more severe WMLs two de- cades later. OR (95% CI) was 4.35 (1.36-13.46) in ordinal regression anal- yses adjusted for age, sex education, follow-up time, presence of the APOEe4 allele, systolic blood pressure, BMI, history of stroke, heart infarct, smoking and level of midlife leisure physical activity. Conclusions: Higher levels of hopelessness at midlife seem to be related to more severe WMLs later in life. Since WMLs may contribute to late-life cognitive impairment, lifestyle management of midlife vascular risk factors (which also increase the risk of dementia and cognitive impairment) may have better effects if people’s expectations are more thoroughly discussed.