| 1. |
- Gil-Bea, Francisco J, et al.
(author)
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Insulin levels are decreased in the cerebrospinal fluid of women with prodomal Alzheimer's disease
- 2010
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In: Journal of Alzheimer's Disease. - Amsterdam; Washington : IOS Press. - 1387-2877 .- 1875-8908. ; 22:2, s. 405-413
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Journal article (peer-reviewed)abstract
- Previous studies have failed to reach consensus on insulin levels in cerebrospinal fluid of Alzheimer's disease (AD) patients and on its relation to pathological features. We performed a new analysis in patients at different stages of AD, and investigated the relationship of insulin levels with biochemical disease markers and with cognitive score. We included 99 patients from our Memory Clinic (Karolinska University Hospital, Sweden), including: 27 patients with mild AD, 13 that progressed from mild cognitive impairment (MCI) to AD in two years time, 26 with MCI stable after two years, and 33 with subjective cognitive impairment. Insulin was significantly decreased in the cerebrospinal fluid of both women and men with mild AD. Insulin deficits were seen in women belonging to both MCI groups, suggesting that this occurs earlier than in men. Insulin was positively associated with amyloid-β 1-42 (Aβ1-42) levels and cognitive score. Furthermore, total-tau/(Aβ1-42*insulin) ratio showed strikingly better sensitivity and specificity than the total-tau/Aβ1-42 ratio for early AD diagnosis in women.
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| 2. |
- Hagman, Göran, et al.
(author)
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Midlife hopelessness and white matter lesions two decades later : A population-based study
- 2010
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In: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 7:4, Supplement, s. 595-595
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Journal article (other academic/artistic)abstract
- 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.
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| 3. |
- Hooshmand, Babak, et al.
(author)
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Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly : a longitudinal study
- 2012
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 271:2, s. 204-212
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Journal article (peer-reviewed)abstract
- Objectives: To examine the associations of serum homocysteine (tHcy), Holotranscobalamin (holoTC), the biologically active fraction of vitamin B12, and folate with cognitive functioning in a longitudinal population-based study of Finnish elderly. Subjects and design: tHcy, holoTC, and folate were measured at baseline in 274 dementia-free subjects aged 65-79 years derived from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study. Subjects were re-investigated 7 years later and global cognition, episodic memory, executive functioning, verbal expression, and psychomotor speed were assessed. Results: Higher baseline tHcy values were associated with poorer performance on global cognition: relative difference (95% confidence interval) was: 0.90 (0.81 - 0.99); episodic memory: 0.87 (0.77 - 0.99); executive functions: 0.86 (0.75 - 0.98), and verbal expression: 0.89 (0.81 - 0.97) at follow-up. Increased holoTC levels were related to better performance on global cognition: 1.09 (1.00 - 1.19), executive functions: 1.11 (1.01 - 1.21), and psychomotor speed: 1.13 (1.01 - 1.26). After excluding 20 incident dementia cases, increased tHcy remained associated with poorer performance in episodic memory, execution functions, and verbal expression. Higher holoTC values tended to relate to better performance in executive functions and psychomotor speed while elevated serum folate concentrations were significantly related to higher scores in global cognition and verbal expression tests. Conclusions: tHcy, holoTC, and folate measured 7 years earlier are related to cognitive performance even in non-demented elderly. Randomized trials are needed to determine the impact of vitamin B12 and folate supplementations on preventing cognitive decline in the elderly.
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| 4. |
- Hooshmand, Babak, et al.
(author)
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Plasma homocysteine, Alzheimer and cerebrovascular pathology : a population-based autopsy study
- 2013
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 136, s. 2707-2716
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Journal article (peer-reviewed)abstract
- Elevated plasma total homocysteine is associated with increased risk of dementia/Alzheimer's disease, but underlying pathophysiological mechanisms are not fully understood. This study investigated possible links between baseline homocysteine, and post-mortem neuropathological and magnetic resonance imaging findings up to 10 years later in the Vantaa 85+ population including people aged epsilon 85 years. Two hundred and sixty-five individuals had homocysteine and autopsy data, of which 103 had post-mortem brain magnetic resonance imaging scans. Methenamine silver staining was used for amyloid-beta and modified Bielschowsky method for neurofibrillary tangles and neuritic plaques. Macroscopic infarcts were identified from cerebral hemispheres, brainstem and cerebellum slices. Standardized methods were used to determine microscopic infarcts, cerebral amyoloid angiopathy, and alpha-synuclein pathology. Magnetic resonance imaging was used for visual ratings of the degree of medial temporal lobe atrophy, and periventricular and deep white matter hyperintensities. Elevated baseline homocysteine was associated with increased neurofibrillary tangles count at the time of death: for the highest homocysteine quartile, odds ratio (95% confidence interval) was 2.60 (1.28-5.28). The association was observed particularly in people with dementia, in the presence of cerebral infarcts, and with longer time between the baseline homocysteine assessment and death. Also, elevated homocysteine tended to relate to amyloid-beta accumulation, but this was seen only with longer baseline-death interval: odds ratio (95% confidence interval) was 2.52 (0.88-7.19) for the highest homocysteine quartile. On post-mortem magnetic resonance imaging, for the highest homocysteine quartile odds ratio (95% confidence interval) was 3.78 (1.12-12.79) for more severe medial temporal atrophy and 4.69 (1.14-19.33) for more severe periventricular white matter hyperintensities. All associations were independent of several potential confounders, including common vascular risk factors. No relationships between homocysteine and cerebral macro- or microinfarcts, cerebral amyoloid angiopathy or alpha-synuclein pathology were detected. These results suggest that elevated homocysteine in adults aged epsilon 85 years may contribute to increased Alzheimer-type pathology, particularly neurofibrillary tangles burden. This effect seems to be more pronounced in the presence of cerebrovascular pathology. Randomized controlled trials are needed to determine the impact of homocysteine-lowering treatments on dementia-related pathology.
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| 5. |
- Hooshmand, Babak, et al.
(author)
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Vitamin D in Relation to Cognitive Impairment, Cerebrospinal Fluid Biomarkers, and Brain Volumes
- 2014
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 69:9, s. 1132-1138
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Journal article (peer-reviewed)abstract
- Background. Low vitamin D status is associated with poorer cognitive function in older adults, but little is known about the potential impact on cerebrospinal fluid (CSF) biomarkers and brain volumes. The objective of this study was to examine the relations between plasma 25-hydroxyvitamin D (25(OH)D) and cognitive impairment, CSF biomarkers of Alzheimer's disease (AD), and structural brain tissue volumes. Methods. A total of 75 patients (29 with subjective cognitive impairment, 28 with mild cognitive impairment, 18 with AD) referred to the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden were recruited. Plasma 25(OH)D, CSF levels of amyloid beta (A beta(1-42)), total-tau, and phosphorylated tau, and brain tissue volumes have been measured. Results. After adjustment for several potential confounders, the odds ratios (95% confidence interval) for cognitive impairment were as follows: 0.969 (0.948-0.990) per increase of 1 nmol/L of 25(OH) D and 4.19 (1.30-13.52) for 24(OH) D values less than 50 nmol/L compared with values greater than or equal to 50 nmol/L. Adjusting for CSF A beta(1-42) attenuated the 25(OH) D-cognition link. In a multiple linear regression analysis, higher 25(OH)D levels were related to higher concentrations of CSF A beta(1-42) and greater brain volumes (eg, white matter, structures belonging to medial temporal lobe). The associations between 25(OH)D and tau variables were not significant. Conclusions. This study suggests that vitamin D may be associated with cognitive status, CSF A beta(1-42) levels, and brain tissue volumes.
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| 6. |
- Kivipelto, Miia, et al.
(author)
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Fokus på tidig diagnos och förebyggande i Alzheimer forskning
- 2013
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In: Finska Läkaresällskapets Handlingar. - Helsingfors. - 0015-2501. ; 173:2, s. 11-19
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Research review (peer-reviewed)abstract
- Alzheimers sjukdom identifieras traditionellt med demenssyndrom. De nya förslagen till diag- noskriterier öppnar ett nytt perspektiv där sjukdomen kan identifieras innan patienterna får demens. Tidig diagnos innebär bättre möjligheter till att hitta effektiva läkemedel och andra demensförebyggande interventioner. Epidemiologiska studier har visat att förutom hög ålder och genetiska faktorer finns det många påverkbara vaskulära, livsstilsrelaterade och psyko- sociala riskfaktorer för Alzheimers sjukdom. I Finland har steget redan tagits från observation till intervention, med fokus på stora multifaktoriella interventionsstudier där flera riskfaktorer och mekanismer påverkas samtidigt (t.ex. FINGER-studien). Tillsammans med två liknande studier i Frankrike och Nederländerna ingår FINGER i European Dementia Prevention Initiative. Resultaten av detta internationella samarbete kommer att leda fram till rekommendationer om en hälsosam livsstil för förebyggande av kognitiv svikt och demens hos äldre. Sådana rekommendationer behövs både för folkhälsan och inom sjukvården.
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| 7. |
- Kivipelto, Miia, et al.
(author)
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Nya kriterier för Alzheimers sjukdom: användning av biomarkörer ger tidigare och mer precis diagnos
- 2011
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In: Läkartidningen. - Stockholm : Läkartidningen förlag. - 0023-7205 .- 1652-7518. ; 108:32-33, s. 1491-1492
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Journal article (peer-reviewed)abstract
- Förslag till nya kriterier för olika stadier av Alzheimers sjukdom har (efter 27 år!) publicerats.De nya riktlinjerna inkluderar användning av nya biomarkörer och ger oss möjlighet att ställa diagnosen »preklinisk alzheimer« relativt långt innan de kliniska symtomen uppträder. Den nya diagnosen preklinisk alzheimer rekommenderas för närvarande endast för forskning.För närvarande saknas sjukdomsmodifierande behandling för alzheimer. Att ställa diagnosen preklinisk alzheimer på en frisk person, om än bara i forskning, blir därför en stor etisk fråga.En annan aspekt är hur hälso- och sjukvårdsapparaten klarar att utreda och ta hand om alla »nya« patienter.Vår slutsats är att kriterierna behöver valideras, men de kommer utan tvekan att leda till en tidigare och mer precis diagnos och dessutom vara till stor nytta när vi förhoppningsvis får nya sjukdomsmodifierande läkemedel.
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| 8. |
- Kivipelto, Miia, et al.
(author)
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The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) : Study design and progress
- 2013
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In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:6, s. 657-665
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Journal article (peer-reviewed)abstract
- Background: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. Materials: Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score >= 6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures. Results: Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014. Conclusions: The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
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| 9. |
- Kivipelto, Miia, et al.
(author)
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Till Klarhet med Alzheimer
- 2013
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In: Äldre i Centrum. Tidskrift för aktuell äldreforskning.. - Stockholm : Äldrecentrum. - 1653-3585. ; 27:4, s. 13-15
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Research review (other academic/artistic)
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| 10. |
- Kulmala, J., et al.
(author)
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Association between mid- to late life physical fitness and dementia : evidence from the CAIDE study
- 2014
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 276:3, s. 296-307
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Journal article (peer-reviewed)abstract
- Objectives. This study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid-to late life and dementia risk. Design. Prospective cohort study. Setting. Cardiovascular risk factors, ageing and incidence of dementia (CAIDE) study. Subjects. Subjects were selected from four independent, random samples of population-based cardiovascular surveys and were first examined in 1972, 1977, 1982 or 1987, when they were on average 50 years old. The CAIDE target population included 3559 individuals. A random sample of 2000 individuals still alive in 1997 was drawn for re-examinations (performed in 1998 and 2005-2008) that consisted of cognitive assessments, with 1511 subjects participating in at least one re-examination. Dementia diagnoses were also confirmed from national registers for the entire target population. Main outcome measure. All-cause dementia. Results. Poor physical fitness at midlife was associated with increased dementia risk in the entire target population [hazard ratio (HR), 1.5; 95% confidence interval (CI), 1.1-2.0]. In participants, odds ratio (OR) was 2.0 (95% CI, 0.9-4.0). This association was significant in apolipoprotein E epsilon 4 allele (APO epsilon 4) noncarriers (OR, 4.3; 95% CI, 1.4-13.3), men (HR, 1.8; 95% CI, 1.1-3.0) and people with chronic conditions (HR, 2.9; 95% CI, 1.3-6.6). A decline in fitness after midlife was also associated with dementia (OR, 3.0; 95% CI, 1.7-5.1), which was significant amongst both men and women and more pronounced in APOE epsilon 4 carriers (OR, 4.4; 95% CI, 2.1-9.1). Conclusions. Perceived poor physical fitness reflects a combination of biological and lifestyle-related factors that can increase dementia risk. A simple question about perceived physical fitness may reveal at-risk individuals who could benefit from preventive interventions.
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