| 1. |
- Enache, Daniela, et al.
(author)
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CAIDE Dementia Risk Score and biomarkers of neurodegeneration in memory clinic patients without dementia
- 2016
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In: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 42, s. 124-131
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Journal article (peer-reviewed)abstract
- The aim of this study was to explore cross-sectional associations between Cardiovascular Risk Factors, Aging and Dementia Study (CAIDE) Dementia Risk Score and dementia-related cerebrospinal fluid and neuroimaging biomarkers in 724 patients without dementia from the Memory Clinic at Karolinska University Hospital, Huddinge, Sweden. We additionally evaluated the score's capacity to predict dementia. Two risk score versions were calculated: one including age, gender, obesity, hyperlipidemia, and hypertension; and one additionally including apolipoprotein E (APOE) ε4 carrier status. Cerebrospinal fluid was analyzed for amyloid β (Aβ), total tau, and phosphorylated tau. Visual assessments of medial temporal lobe atrophy (MTA), global cortical atrophy-frontal subscale, and Fazekas scale for white matter changes (WMC) were performed. Higher CAIDE Dementia Risk Score (version without APOE) was significantly associated with higher total tau, more severe MTA, WMC, and global cortical atrophy-frontal subscale. Higher CAIDE Dementia Risk Score (version with APOE) was associated with reduced Aβ, more severe MTA, and WMC. CAIDE Dementia Risk Score version with APOE seemed to predict dementia better in this memory clinic population with short follow-up than the version without APOE.
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| 2. |
- 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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| 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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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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| 5. |
- 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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| 6. |
- 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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| 7. |
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| 8. |
- Solomon, Alina, et al.
(author)
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Practical Lessons from Amyloid Immunotherapy Trials in Alzheimer Disease
- 2012
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In: Current Alzheimer Research. - : Bentham Science Publishers Ltd.. - 1567-2050 .- 1875-5828. ; 9:10, s. 1126-1134
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Journal article (peer-reviewed)abstract
- Objectives: Amyloid immunotherapy trials are central in Alzheimer disease (AD) drug development, with the potential to influence all future disease-modifying randomized controlled trials (RCTs). This study investigates practical experiences of staff and participants in immunotherapy RCTs. Setting and methods: The Clinical Trial Research Unit of the Memory Clinic at Karolinska University Hospital, Sweden is an experienced centre specialized in Alzheimer RCTs, where four active and passive phase I/II immunotherapy trials are currently ongoing. Meetings were held with staff members, who were asked to describe their experiences and suggest necessary improvements. In addition, a pilot study was conducted to investigate motivations and expectations of participants in immunotherapy RCTs. A questionnaire was sent to 20 patients, and another similar questionnaire to their caregivers. Results: The main issues emphasized by staff members concerned the critical window of opportunity for recruiting RCTs participants, the much higher level of effort required of patients and caregivers in immunotherapy RCTs compared to classical cholinesterase inhibitor RCTs, problematic informed consent procedures, and confidentiality limitations in trials with different sponsors. For patients and caregivers, the main reason for participating in RCTs was the wish to help research and other people, followed by the need for information, continuity of care, safety and support. Compared to patients, caregivers' expectations of trial results were more realistic. Conclusions: More open debates of practical experiences from different trial centres and sponsors are essential for optimizing trial designs and improving conditions for participants.
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