Showing papers by "Miia Kivipelto published in 2006"

Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study.

Abstract: Summary Background Several vascular risk factors are associated with dementia. We sought to develop a simple method for the prediction of the risk of late-life dementia in people of middle age on the basis of their risk profiles. Methods Data were used from the population-based CAIDE study, which included 1409 individuals who were studied in midlife and re-examined 20 years later for signs of dementia. Several midlife vascular risk factors were studied to create the scoring tool. The score values were estimated on the basis of β coefficients and the dementia risk score was the sum of these individual scores (range 0–15). Findings Occurrence of dementia during the 20 years of follow-up was 4%. Future dementia was significantly predicted by high age (≥47 years), low education ( Interpretation The dementia risk score is a novel approach for the prediction of dementia risk, but should be validated and further improved to increase its predictive value. This approach highlights the role of vascular factors in the development of dementia and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions.

Fat intake at midlife and risk of dementia and Alzheimer's disease: a population-based study.

Abstract: Background: Lifestyle and vascular factors have been linked to dementia and Alzheimer’s disease (AD), but the role of dietary fats in the development of dementia is less clear. <

Body mass index and the risk of Parkinson disease

Abstract: Objective: To examine the association between body mass index (BMI) and the risk of Parkinson disease (PD). Methods: Study cohorts included 22,367 Finnish men and 23,439 women 25 to 59 years of age without a history of PD at baseline. Hazards ratios (HRs) of incident PD were estimated for different levels of BMI. Results: During a mean follow-up period of 18.8 years, 272 men and 254 women developed incident PD. After adjustment for confounding factors (age, study years, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, and alcohol, coffee, and tea consumption), the HRs of PD at different levels of BMI ( Conclusion: Body mass index is associated with a risk of Parkinson disease. The effect is graded and independent of other risk factors.

Clinical trials in mild cognitive impairment: lessons for the future

Abstract: Mild cognitive impairment (MCI) is an operational definition for a cognitive decline in individuals with a greater risk of developing dementia. The amnestic subtype of MCI is of particular interest because these individuals most likely progress to Alzheimer's disease (AD). Currently hypothesised therapeutic approaches in MCI are mainly based on AD treatment strategies. Long term secondary prevention randomised clinical trials have been completed in amnestic MCI populations, encompassing agents with various mechanisms of action: acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine), antioxidants (vitamin E), anti‐inflammatories (rofecoxib), and nootropics (piracetam). The design of clinical trials in MCI is influenced by study objectives and definition of primary end points: time to clinical diagnosis of dementia, and AD in particular, or symptom progression. As none of the drugs previously shown to have clinical efficacy in AD trials or benefit in everyday practice have met the primary objectives of the respective trials, design of future clinical trials in MCI should be further developed particularly as regards the selection of more homogeneous samples at entry, optimal treatment duration, and multidimensional and reliable outcomes.

Cholesterol as a risk factor for Alzheimer's disease – epidemiological evidence

Abstract: Although dementia is usually a late-life syndrome, it is now well known that pathological changes begin quite early in adulthood, outside the classical age borders of geriatric specialties. In order to design effective preventive strategies, adequate information can only be gathered by taking a life-long view of Alzheimer's disease (AD). Dementia risk is the result of exposure to both harmful and protective factors along the life course, and these factors, as well as their impact on the individual's health status, change over time. This review aims at presenting current epidemiological data on serum cholesterol levels and dietary fat intake as risk factors for dementia/AD, and at discussing the reasons and significance of contradictions between various studies. Reducing dementia risk may be possible by influencing the serum lipid profile. A more detailed characterization of the mechanisms behind the association of cholesterol (in both serum and brain) with dementia/AD, mechanisms about which little is currently known, would allow a better translation of research findings into clinical practice.

Rethinking the dementia diagnoses in a population-based study: what is Alzheimer's disease and what is vascular dementia?. A study from the kungsholmen project.

Abstract: Objective: To explore the hypothesis that older adults often are affected by more than one disease, making the differential diagnosis between Alzheimer’s disease (AD) and vascular dementia (VaD) difficult. Methods: Incident dementia cases (n = 308) from a population-based longitudinal study of people 75+ years were investigated. The DSM-III-R criteria were used for the clinical diagnosis of dementia. Data on vascular disorders (hypertension, cerebrovascular and ischemic heart diseases, heart failure, atrial fibrillation, diabetes) as well as type of onset/course of dementia were used retrospectively to reclassify dementias. Results: Only 47% of the AD cases were reclassified as pure AD without any vascular disorder. Among subjects with AD and with a vascular component, cerebrovascular disease was the most common (41%). Only 25% of VaD were reclassified as pure VaD. Further, 26% of the pure AD subjects developed a vascular disorder in the following 3 years. Conclusions: Both vascular and degenerative mechanisms may often contribute to the expression of dementia among the elderly. Most of the AD cases have vascular involvements, and pure dementia types in very old subjects constitute only a minority of dementia cases.

The Effect of Apolipoprotein Polymorphism on Brain in Mild Cognitive Impairment: A Voxel-Based Morphometric Study

Abstract: We investigated the effect of apolipoprotein E (ApoE) on the whole brain in 51 individuals with mild cognitive impairment using voxel-based morphometry. Between cases heterozygous for the ApoE E4 (n = 15) and those who were ApoE E4 noncarriers (n = 28), only the right parahippocampal gyrus, with the entorhinal cortex included, reached the level of statistical significance. In cases homozygous for the E4 allele (n = 8) versus noncarriers, the greatest atrophy was located in the right amygdala followed by the right parahippocampal gyrus, the left amygdala and the left medial dorsal thalamic nucleus.

The new cholesterol controversy – a little bit of history repeating?

Abstract: The most exciting phrase to hear in science, the one that heralds new discoveries, is not Eureka! (I found it!) but rather, ‘hmm… that's funny….’ Isaac Asimov

Cerebral embolism and Alzheimer's disease.

Abstract: Until recently, advanced age and genes were the only well established risk factors for Alzheimer's disease; hence it has not been possible to develop preventive strategies. Now, evidence of modifiable risk factors for Alzheimer's disease is increasing. On p 1119, Purandare and colleagues report an association between spontaneous cerebral emboli and dementia.1 This case-control study provides evidence for the longlasting debate on the causes of Alzheimer's disease versus those of vascular dementia. Purandare and colleagues used transcranial Doppler to detect spontaneous cerebral emboli, monitoring patients with Alzheimer's disease, patients with vascular dementia, and age and sex matched controls for an hour. These emboli were detected significantly more frequently in patients with dementia, and the frequency was similar in Alzheimer's disease and vascular dementia. This study thus joins a series of articles that have pointed out a necessary shift from the concept of two sharply separated types of dementia to a dementia spectrum, with pure Alzheimer's disease and pure vascular dementia at the extremes and a mixture of the two in various degrees as the rule rather than the exception. One of the main characteristics of research on dementia has been the tendency to separate neurodegenerative and vascular pathology. However, the complexity of the relation between the two main subtypes is now obvious, as more and more research data show considerable overlap in risk factors, neuropathology, and clinical features. Several epidemiological studies have suggested an association between Alzheimer's disease and vascular risk factors including hypertension, hypercholesterolemia, obesity, diabetes mellitus, dietary fat intake, and physical inactivity.2,3 Moreover, carotid atherosclerosis4 and atrial fibrillation,5 two important sources of spontaneous cerebral emboli, have also been suggested as risk factors for dementia. The coexistence of Alzheimer's-type changes and vascular neuropathological changes seems to be more common than would be expected by chance alone, and the two types of pathology have a synergistic effect, rather than simply additive effect, on the expression of dementia.6 In addition, studies comparing neuropathological findings at autopsy with clinical diagnoses of dementia indicate important discrepancies between clinical labels and pathological reality.7 The typical clinical picture of Alzheimer's disease includes a long preclinical phase with an insidious onset of dementia, while the classical description of cognitive decline due to vascular causes comprises a stepwise onset and course. While there are cases that match this classical representation, in many situations identifying a date of onset proves impossible.8 For example, large emboli may cause clinically visible strokes and lead to textbook cases of multi-infarct dementia, but small and clinically silent emboli occurring repeatedly over several months or years tend to cause slowly progressive brain damage and cognitive deficits. The study by Purandare and colleagues is cross sectional and cannot draw a definite conclusion about cause and effect. The authors did not find any direct association between spontaneous cerebral emboli and cardiovascular risk factors (including carotid atherosclerosis and atrial fibrillation) in patients with dementia, implying that spontaneous cerebral emboli may be a universal phenomenon in dementia. But what mechanisms would lie behind an association between such emboli and dementia? It has to be kept in mind that factors such as blood pressure, serum cholesterol concentration, and body mass index often decline before dementia becomes obvious,3 perhaps as a consequence of the disease, which may attenuate their effect in a cross sectional design. Indeed, Purandare and colleagues mention that body mass index was lower in both groups of patients with dementia than in the control group. Even if this study leaves the question of mechanisms unanswered, it emphasises one very important issue related to preventing and treating dementia. The classical view of dementia has strongly influenced therapeutic approaches, making it difficult to tailor treatments to patients' various needs. If the diagnosis is vascular dementia, treatment aimed at cognitive impairment is sometimes overlooked, and if the diagnosis is Alzheimer's disease, vascular factors may be overlooked. Artificially labelling patients with one single diagnosis is less helpful than trying to identify and treat all possible aetiopathogenic factors. Early and effective treatment of vascular risk factors may have positive effects not only for cardiac health but may also help in preventing or postponing the onset of dementia.

Alzheimer's Disease: back to the future

Abstract: Looking on the panorama of so many past and current scientific results and achievements, we may feel that we have moved ahead considerably. But the sobering fact still remains that, although we have provided some help to many individuals with Alzheimer’s disease (AD) by our diagnostic and therapeutic advances, we have not thus far effectively treated the disease or reduced the problem as it affects the whole population. The majority of AD cases are sporadic, but the image we have of this disease has been strongly influenced by research on the familial AD type (which accounts for only 1–2% of all cases). The inherited form is mainly the result of an interaction between genes and proteins. It is however much more clear now that what we call AD is not a single nosological entity, as the sporadic AD type differs from the familial type and presents considerable heterogeneity in terms of risk factor profiles, pathogenesis and neuropathological findings. In this markedly multifactorial sporadic AD, the involvement of lipids (from both plasma and brain) should not be underestimated, even if we are still used to talking first about genes and proteins. It took several decades for data on peripheral lipid metabolism to emerge, and it will (again) take time to elucidate brain lipid metabolism and the interactions between the two lipid pools. However, we have good reasons to believe that this research process may advance at a much faster pace, as was illustrated by the articles in the Supplement presenting significant findings about oxysterols, lipid rafts and the involvement of cholesterol in AD pathology. Deeper understanding about cholesterol homeostasis disturbances in AD will hopefully lead to effective interventional tools and markers for early detection and monitoring of the disease. New risk factors, new diagnostic markers, new therapeutic targets and new treatments will probably be discovered on the way. But what is most important at this point is a new sight of old views. It is well known that clinicians tend to feel more confident in formulating case management strategies when they succeed in applying a clear diagnostic label to the patient. This can however lead to an oversimplification of reality. Trying to determine with certainty whether the diagnosis is AD or vascular dementia is less beneficial for the patient than trying to identify all aetiopathogenic factors involved. As many studies have already shown, mixed pathology is the rule, rather than the exception, in dementia. And even if AD type and vascular changes are both so common that they inevitably occur together in many cases, their relationship appears to be far more complex, as there is considerable overlapping in risk factors, clinical features and neuropathology. We do not know yet to what extent these changes are coincidental, contributory or causal, but the concept of a dementia spectrum (from purely degenerative to combinations of AD type and vascular changes in different degrees to purely vascular) seems now more adequate than the previous dichotomy. Diagnostic criteria need to be adjusted to this updated image of reality. The classical view vascular vs degenerative diseases has also strongly influenced dementia therapy, making it difficult to tailor treatments to the patients various needs. If the diagnosis is vascular dementia, there is a chance that cognition-directed treatment is overlooked, while if the diagnosis is AD, vascular changes may be overlooked. Kivipelto M, Solomon A, Winblad B. Alzheimer’s Disease: back to the future. Acta Neurol Scand 2006: 114 (Suppl. 185): 119–120. Blackwell Munksgaard 2006. M. Kivipelto, A. Solomon, B. Winblad Department of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland

P3-125: Fat intake at midlife and cognitive impairment later in life: A population-based study

Abstract: derly subjects, 906 households were eligible and 682 subjects participated. Subjective memory complaints were assessed by subjective memory complaint questionnaire (SMCQ), which consists of 14 items reflecting general memory function and everyday memory function. Variables associated with SMC including cognitive function, depressive symptoms, hearing impairment and daytime sleepiness were evaluated by trained research nurses using Geriatric Health Assessment Package (GHAP). Bivariate associations between SMCQ and clinical variables were investigated using simple linear regression analysis. To determine which variables were independently associated with SMCQ and its two subscales, stepwise multiple linear regression analysis was performed for each scale. Results: The following were associated with SMC in simple linear regression analysis: cognitive function, depressive symptoms, visual and hearing impairment, excessive daytime sleepiness, activities of daily living function, history of urinary incontinence, fall and pain (p 0.05). In stepwise multiple linear regression analysis, excessive daytime sleepiness and hearing impairment were independently and consistently associated with SMC after controlling for objective cognitive function and depressive function. Moreover, these noncognitive variables were stronger predictors of SMC than objective cognitive function. Conclusions: Among elderly subjects in the general population, noncognitive variables including daytime sleepiness and hearing impairment were associated with SMC independent of depression and objective cognitive function. Moreover, association of SMC with daytime sleepiness and hearing impairment was stronger than that of cognitive function. Our results suggested that SMC are not a simple reflection of objective cognitive function. Thus, clinicians should carefully evaluate the multiple noncognitive domains when elderly subjects report memory complaints.

S1-01-06

Abstract: Cognitive impairment affects at least 10% of elders aged 65 years and older, increasing in prevalence to 50% of elders 85 years of age and older. In hopes of identifying agents that may prevent cognitive impairment, there has been tremendous interest in the role of both exogenous and endogenous hormones and risk of Alzheimer’s disease (AD) and pre-clinical cognitive decline, especially in women. Indeed, estogen receptors (ER) (both ER and ER ) are located throughout the brain, especially in regions involved in learning and memory such as the hippocampus and amygdala. However, studies in women involving estrogens have been conflicting with the predonderance of observational studies suggesting benefit and the randomized trials suggesting no benefit and possible harm. We will review the current evidence of the effect of exogenous estrogen and the risk of developing dementia. In addition, we will discuss results from studies of selective estrogen receptor modulators (SERMs) and highlight areas of future research with these and other novel estrogenic compounds. We will also review the literature on endogenous estrogens and cognitive function and risk of AD and suggest future directions for research.