Lars Bäckman

The betula prospective cohort study: Memory, health, and aging

Abstract The objective of this article is to present an overview of a prospective cohort study involving a total of 3,000 subjects whose ages were 35, 40, 45, 50, 55, 60, 65, 70, 75, and 80 years when first tested. the design of the study includes three waves of data collection. the first of these waves was conducted in 1988-1990, the second in 1993-1995, and the third will be conducted in 1998-2000. One sample of 1,000 subjects in these age cohorts underwent testing in 1988-1990 (100 subjects per cohort). This sample and two additional samples were tested in 1993-1995 and will be tested again in 1998-2000. Subjects take part in extensive health and memory examinations, and interviews about social factors. the memory testing covers a wide range of memory functions. the chief objectives of the study are to (a) examine the development of health and memory in adulthood and old age; (b) determine early preclinical signs of dementia; (c) determine risk factors for dementia; and (d) assess premorbid memory func...

Age-related differences in white matter microstructure: Region-specific patterns of diffusivity

We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

The occurrence of depressive symptoms in the preclinical phase of AD: A population-based study

Objective: To examine preclinical depressive symptoms 3 years before the diagnosis of AD. Methods: The authors compared incident AD patients and nondemented individuals in terms of baseline mood- and motivation-related symptoms of depression, and assessed whether depressive symptoms in preclinical AD are related to self-perceived memory problems. Participants came from a population-based longitudinal study on aging and dementia in Stockholm, Sweden. The sample consisted of 222 persons older than 74 years who were followed for a 3-year interval. Thirty-four individuals had developed AD at follow-up, whereas 188 remained nondemented. Dementia diagnosis was made according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised. Depressive symptoms were assessed by the Comprehensive Psychopathological Rating Scale. Results: The incident AD patients had more depressive symptoms than the nondemented persons at baseline. There was a dominance of motivation-related symptoms of depression (e.g., lack of interest, loss of energy, concentration difficulties) in preclinical AD. This association remained when adjusting for subjective memory complaints. Conclusions: Depressive symptoms are elevated preclinically in AD, and this elevation is not merely a by-product of self-perceived cognitive difficulties. Thus, depressive symptoms may be part of the preclinical phase in AD.

Linking cognitive aging to alterations in dopamine neurotransmitter functioning : Recent data and future avenues

Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D(1) and D(2) receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused review targets several recent findings pertaining to these relationships. Specifically, we discuss novel evidence concerning (a) the role of DA in within-person cognitive variability; (b) age-related differences in DA release during cognitive processing; (c) DA release following cognitive training in younger and older adults; and (d) the relationship between DA and task-induced functional brain activity. Based on these lines of empirical inquiry, we outline a series of avenues for future research on aging, DA, and cognition.

Twenty-year changes in dementia occurrence suggest decreasing incidence in central Stockholm, Sweden

Objective: To explore whether prevalence, survival, and incidence of dementia have changed from 1987–1994 to 2001–2008 in Stockholm, Sweden. Methods: This study is based on 2 cross-sectional surveys of people aged 75 years or over conducted in central Stockholm: the Kungsholmen Project (KP) (1987–1989, n = 1,700) and the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) (2001–2004, n = 1,575). In both surveys we diagnosed dementia according to DSM-III-R criteria, following the identical diagnostic procedure. Death certificates were used to determine survival status of KP participants as of December 1994 and SNAC-K participants as of June 2008. We used logistic and Cox models to compare prevalence and survival, controlling for major confounders. We inferred incidence of dementia according to its relationship with prevalence and survival. Results: At baseline, 225 subjects in KP and 298 in SNAC-K were diagnosed with dementia. The age- and sex-standardized prevalence of dementia was 17.5% (12.8% in men; 19.2% in women) in KP and 17.9% (10.8% in men; 20.5% in women) in SNAC-K. The adjusted odds ratio of dementia in SNAC-K vs KP was 1.17 (95% confidence interval 0.95–1.46). The multiadjusted hazard ratio of death in SNAC-K vs KP was 0.71 (0.57–0.88) in subjects with dementia, 0.68 (0.59–0.79) in those without dementia, and 0.66 (0.59–0.74) in all participants. Conclusions: Prevalence of dementia was stable from the late 1980s to the early 2000s in central Stockholm, Sweden, whereas survival of patients with dementia increased. These results suggest that incidence of dementia may have decreased during this period.

Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study

Abstract Objectives: To evaluate a simple three step procedure to identify people in the general population who are in the preclinical phase of Alzheimers disease and dementia. Design: Three year population based cohort study. Setting: Kungsholmen cohort, Stockholm, Sweden. Participants: 1435 people aged 75–95 years without dementia. Assessments: Single question asking about memory complaints, assessment by mini-mental state examination, and neuropsychological testing. Main outcome measure: Alzheimers disease and dementia at three year follow up. Results: None of the three instruments was sufficiently predictive of Alzheimers disease and dementia when administered separately. After participants had been screened for memory complaints and global cognitive impairment, specific tests of word recall and verbal fluency had positive predictive values for dementia of 85-100% (95% confidence intervals range from 62% to 100%). However, only 18% of future dementia cases were identified in the preclinical phase by this three step procedure. Memory complaints were the most sensitive indicator of Alzheimers disease and dementia in the whole population, but only half the future dementia cases reported memory problems three years before diagnosis. Conclusion: This three step procedure, which simulates what might occur in clinical practice, has a high positive predictive value for dementia, although only a small number of future cases can be identified. What is already known on this topic Alzheimers disease is characterised by a preclinical phase, during which cognitive deficits are seen before diagnosis Elderly people with subjective memory complaints and objective global cognitive impairment have a high risk of developing Alzheimers disease and dementia What this study adds This three step procedure (self report of memory complaints, test of global cognitive functioning, and then domain specific cognitive tests) has a positive predictivity of 85-100% for Alzheimers disease and dementia at three years However, only 18% of people in the preclinical phase can be identified using this procedure About half of the people in the preclinical phase of Alzheimers disease and dementia do not report problems with their memory three years before diagnosis

Performance level modulates adult age differences in brain activation during spatial working memory

Working memory (WM) shows pronounced age-related decline. Functional magnetic resonance imaging (fMRI) studies have revealed age differences in task-related brain activation. Evidence based primarily on episodic memory studies suggests that brain activation patterns can be modulated by task difficulty in both younger and older adults. In most fMRI aging studies on WM, however, performance level has not been considered, so that age differences in activation patterns are confounded with age differences in performance level. Here, we address this issue by comparing younger and older low and high performers in an event-related fMRI study. Thirty younger (20–30 years) and 30 older (60–70 years) healthy adults were tested with a spatial WM task with three load levels. A region-of-interest analysis revealed marked differences in the activation patterns between high and low performers in both age groups. Critically, among the older adults, a more “youth-like” load-dependent modulation of the blood oxygen level-dependent signal was associated with higher levels of spatial WM performance. These findings underscore the need of taking performance level into account when studying changes in functional brain activation patterns from early to late adulthood.

Prerequisites for lack of age differences in memory performance

Free recall performance of young and old adults was examined in three memory tasks: acts carried out by the subjects (subject-performed tasks or SPTs), sentences with imagery instructions, and sentences. The subjects were presented with the same verbal information in all three tasks. No age differences were observed on free recall of SPTs, whereas typical aging effects were obtained on free recall of the other tasks. This way the data from a previous study of no age effects on SPT recall were replicated. A hypothesis about imagery as a critical factor for the lack of age differences on SPT recall gained no support. Two main concepts were proposed to account for the data: Compensation among the elderly by means of the multimodal and rich properties of SPTs, and a superior ability for a spontaneous recoding of verbal information among young adults. The results were also discussed in relation to a presumption of memory tasks as varying in attentional demands.

Recognition memory across the adult life span: the role of prior knowledge.

Two experiments were performed to investigate the effects of prior knowledge on recognition memory in young adults, younger old adults, 76-year-olds, and 85-year-olds. In Experiment 1, we examined episodic recognition of dated and contemporary famous persons presented as faces, names, and faces plus names. In Experiment 2, four types of faces were presented for later recognition: dated familiar, contemporary familiar, old unfamiliar, and young unfamiliar. The results of both experiments showed that young adults performed better with contemporary than with dated famous persons, whereas the reverse was true for all groups of older adults. In addition, the data of Experiment 2 indicated that (1) young adults showed better recognition for young than for old unfamiliar faces, (2) younger old adults performed better with old than with young unfamiliar faces, and (3) the two oldest age groups showed no effect of age of face. These results suggest that the ability to utilize rich semantic knowledge to improve episodic memory is preserved in very old age, although the aging process may be associated with deficits in the ability to utilize prior knowledge to support memory when the underlying representation lacks semantic and contextual features. The overall data pattern was discussed in relation to the notion that, with increasing adult age, there is an increase in the level of cognitive support required to enhance episodic remembering.

Accelerated Progression from Mild Cognitive Impairment to Dementia in People with Diabetes

OBJECTIVE The effect of diabetes on mild cognitive impairment (MCI) and its conversion to dementia remains controversial. We sought to examine whether diabetes and pre-diabetes are associated with MCI and accelerate the progression from MCI to dementia. RESEARCH DESIGN AND METHODS In the Kungsholmen Project, 963 cognitively intact participants and 302 subjects with MCI (120 with amnestic MCI [aMCI ] and 182 with other cognitive impairment no dementia [oCIND]) age ≥75 years were identified at baseline. The two cohorts were followed for 9 years to detect the incident MCI and dementia following international criteria. Diabetes was ascertained based on a medical examination, hypoglycemic medication use, and random blood glucose level ≥11.0 mmol/l. Pre-diabetes was defined as random blood glucose level of 7.8–11.0 mmol/l in diabetes-free participants. Data were analyzed using standard and time-dependent Cox proportional-hazards models. RESULTS During the follow-up period, in the cognitively intact cohort, 182 people developed MCI (42 aMCI and 140 oCIND), and 212 developed dementia. In the MCI cohort, 155 subjects progressed to dementia, the multi-adjusted hazard ratio (95% CI) of dementia was 2.87 (1.30–6.34) for diabetes, and 4.96 (2.27–10.84) for pre-diabetes. In a Kaplan-Meier survival analysis, diabetes and pre-diabetes accelerated the progression from MCI to dementia by 3.18 years. Diabetes and pre-diabetes were neither cross-sectionally nor longitudinally associated with MCI. CONCLUSIONS Diabetes and pre-diabetes substantially accelerate the progression from MCI to dementia, and anticipate dementia occurrence by more than 3 years in people with MCI. The association of diabetes with the development of MCI is less evident in old people.