| 1. |
- Voevodskaya, Olga, et al.
(författare)
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Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease
- 2016
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 86:19, s. 1754-1761
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We aimed to test whether in vivo levels of magnetic resonance spectroscopy (MRS) metabolites myo-inositol (mI), N-acetylaspartate (NAA), and choline are abnormal already during preclinical Alzheimer disease (AD), relating these changes to amyloid or tau pathology, and functional connectivity.METHODS: In this cross-sectional multicenter study (a subset of the prospective Swedish BioFINDER study), we included 4 groups, representing the different stages of predementia AD: (1) cognitively healthy elderly with normal CSF β-amyloid 42 (Aβ42), (2) cognitively healthy elderly with abnormal CSF Aβ42, (3) patients with subjective cognitive decline and abnormal CSF Aβ42, (4) patients with mild cognitive decline and abnormal CSF Aβ42 (Ntotal = 352). Spectroscopic markers measured in the posterior cingulate/precuneus were considered alongside known disease biomarkers: CSF Aβ42, phosphorylated tau, total tau, [(18)F]-flutemetamol PET, f-MRI, and the genetic risk factor APOE.RESULTS: Amyloid-positive cognitively healthy participants showed a significant increase in mI/creatine and mI/NAA levels compared to amyloid-negative healthy elderly (p < 0.05). In amyloid-positive healthy elderly, mI/creatine and mI/NAA correlated with cortical retention of [(18)F] flutemetamol tracer ([Formula: see text] = 0.44, p = 0.02 and [Formula: see text] = 0.51, p = 0.01, respectively). Healthy elderly APOE ε4 carriers with normal CSF Aβ42 levels had significantly higher mI/creatine levels (p < 0.001) than ε4 noncarriers. Finally, elevated mI/creatine was associated with decreased functional connectivity within the default mode network (rpearson = -0.16, p = 0.02), independently of amyloid pathology.CONCLUSIONS: mI levels are elevated already at asymptomatic stages of AD. Moreover, mI/creatine concentrations were increased in healthy APOE ε4 carriers with normal CSF Aβ42 levels, suggesting that mI levels may reveal regional brain consequences of APOE ε4 before detectable amyloid pathology.
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| 2. |
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| 3. |
- Nägga, Katarina, 1962-
(författare)
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Aspects on clinical diagnosis of dementia, with focus on biological markers
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The clinical dementia diagnosis has become more complex with increasing knowledge of the heterogeneity of the disorder and its different aetiological aspects. A clinical dementia population and a control group were investigated with the following aims: I. To study the CSF levels of tau phosphorylated at threonine 181 (P-tau), total tau (T-tau) and ß-amyloid1-42 (Aß42) in the different diagnoses. II. To study associations between dementia disorder, cobalamin and/or folate deficiency, and gastritis. III. To study the presence and severity of CT brain changes in different dementia diagnoses. IV. To investigate to what extent different biomarkers and disease history contribute to the diagnostics of clinical dementia.I. CSF Levels of P-tau, T-tau and Aß42 were analysed with ELISA methods. Elevated CSF levels of P-tau were found in probable Alzheimer's disease (AD) patients compared with cognitively non-disturbed controls. Increased CSF T-tau, and decreased levels of Aß42 were found in both AD, mixed type of dementia, and vascular dementia (VaD) patients compared with the controls. Increased P-tau levels were more specific for AD pathology, but there was still an overlap with the controls, mixed dementia and VaD patients.II. Serological markers for cobalamin and folate deficiencies, and for gastritis were assessed in patients with different dementia diagnoses. Hyperhomocysteinaemia were commonly found in dementia without predominance in any of the investigated categories. Low levels of serum cobalamin or blood folate rarely reflected the elevated Hey levels. A lack of association between serological markers for cobalamin and folate deficiencies and for gastritis was demonstrated.III. A protocol for evaluation of the CT scans was used. Atrophy on the CT scans, although common in dementia, is an unspecific fmding in dementia of different backgrounds. White-matter changes and lacunes, indicating small-vessel disease, were common in dementia of different aetiologies. Dementia of mixed-type pathology was underestimated. More distinct criteria for this diagnostic category are warranted.IV. Partial Least Squares Discriminant Analysis (PLS-DA) was used on a large number of variables covering cognitive and biological markers and disease history. There were good discriminations of subgroups of dementia from the controls. However, the included variables were not able to distinguish between the investigated groups, indicating that several clinical parameters used in diagnosing dementia are in fact observed across different subtypes of dementia.It is concluded that there are no known biomarkers available that can provide a precise differential diagnosis of dementia. The clinical dementia diagnosis must still be based on a combination of a careful disease history, evaluation of risk factors, symptomatology, clinical findings, neurocognitive tests, blood analysis and other available methods such as CT and CSF markers.
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| 4. |
- Nägga, Katarina, et al.
(författare)
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Cerebral inflammation is an underlying mechanism of early death in Alzheimer's disease : a 13-year cause-specific multivariate mortality study
- 2014
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Ingår i: Alzheimer's Research & Therapy. - : BioMed Central. - 1758-9193. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Although Alzheimer's disease (AD) is associated with early death, its life expectancy differs greatly between patients. A better understanding of this heterogeneity may reveal important disease mechanisms underlying the malignancy of AD. The aim of this study was to examine the relation between AD pathologies and early death in AD caused by dementia.METHODS: At a memory clinic, 247 referred consecutive patients with AD were monitored during 12.6 ± 1.6 years. Multivariate Cox regression analyses were performed with baseline measures of amyloid beta (Aβ) pathology (APOE genotype, cerebrospinal fluid (CSF) Aβ42) tau pathology (CSF phosphorylated tau and total tau), cerebrovascular pathology (white-matter lesions and CSF/serum albumin ratio), neuroinflammatory pathology (CSF soluble vascular cell adhesion molecule-1, sVCAM-1), frontal, temporal, and central brain atrophies, global cognition, sex, and age. Comorbidities and medications also were analyzed. All continuous variables were transformed to z scores to compare hazard ratios (HRs) and 95% confidence intervals (CIs).RESULTS: At follow-up, 89% of the patients had died. The mean survival time was 6.4 ± 3.0 years. The AD pathology that independently predicted an early death caused by dementia was cerebral inflammation (sVCAM-1; HR, 1.32; 95% CI, 1.07-1.64). Other independent predictors were lower global cognition (HR, 0.51; 95% CI, 0.43-0.61), frontal atrophy (HR, 1.38; 95% CI, 1.12-1.70), and medial temporal atrophy (HR, 1.23; 95% CI, 1.02-1.49). When examining death caused by dementia and related causes (vascular diseases and infections), age (HR, 1.23; 95% CI, 1.04-1.46) and cerebrovascular pathology (white-matter lesions: HR, 1.17; 95% CI, 1.01-1.36; and CSF/serum albumin ratio: HR, 1.16; 95% CI, 1.001-1.34) were also significant risk factors in addition to the previous variables. No comorbidity or medication was significant in the specific-cause models.CONCLUSIONS: This is the first study to link neuroinflammation independently to early death in AD and, hence, a rapidly progressing disease. Frontal and medial temporal atrophies and low cognition were also significant predictors. These are probably downstream biomarkers that reflect neuronal degeneration and late-stage disease. Our results suggest that inflammation, and not amyloid or tau pathology, is an independent underlying mechanism in the malignancy of AD.
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| 5. |
- Palmqvist, Sebastian, et al.
(författare)
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Association between subcortical lesions and behavioral and psychological symptoms in patients with Alzheimer's disease
- 2011
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 32:6, s. 417-423
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: The most devastating features of Alz-heimer's disease (AD) are often the behavioral and psychological symptoms in dementia (BPSD). There is controversy as to whether subcortical lesions contribute to BPSD. The aim of this study was to examine the relationship between BPSD and subcortical lesions (white-matter lesions and lacunes) in AD.METHODS: CT or MRI from 259 patients with mild-to-moderate AD were assessed with the Age-Related White Matter Changes scale. Linear measures of global and temporal atrophy and Mini-Mental State Examination scores were used to adjust for AD pathology and disease severity in logistic regression models with the BPSD items delusions, hallucinations, agitation, depression, anxiety, apathy and irritability.RESULTS: Lacunes in the left basal ganglia were associated with delusions (OR 2.57, 95% CI 1.21-5.48) and hallucinations (OR 3.33, 95% CI 1.38-8.01) and lacunes in the right basal ganglia were associated with depression (OR 2.13, 95% CI 1.01-4.51).CONCLUSION: Lacunes in the basal ganglia resulted in a 2- to 3-fold increased risk of delusions, hallucinations and depression, when adjusting for cognition and atrophy. This suggests that basal ganglia lesions can contribute to BPSD in patients with AD, independently of the AD process.
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| 6. |
- Westerlind, Björn, 1961-
(författare)
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Geriatric Aspects of Frail Nursing Home Residents : A Swedish cohort study
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The number and proportion of older people are increasing in Sweden as well as throughout the western world. Older people with increasing assistance needs that can no longer be met in their own home need institutional long-term care in nursing homes. A successive reduction of nursing home beds in combination with a future demographic development with a rapidly increasing number of older people will lead to higher demands on future medical care in nursing homes. Consequently, increased knowledge about the medical needs of nursing home residents is of great value.Objectives: This thesis explores some important geriatric aspects of frail nursing home residents. The specific aims was to characterise the population of nursing home residents, to explore the prevalence of anaemia, paying particular attention to risk factors and mortality, to investigate associations between falls and use of possible fall risk drug classes and to estimate the prevalence of diagnostic failure of cognitive impairment and to investigate whether diagnostic failure was associated with impaired medical care.Methods: All data originate from SHADES (the Study of Health and Drugs in Elderly nursing home residents in Sweden), a prospective cohort study that included nursing home residents at 12 nursing homes situated in three municipalities in southern Sweden between 2008 and 2011. The subjects were followed every six months with data collection from medical records concerning medications, diagnoses, hospital referrals and mortality, examinations including blood sample analyses, assessments with validated rating scales for cognitive evaluation, depression, risk of pressure ulcers, malnutrition or falls, and the need for care was rated through a questionnaire.Results: SHADES included a total of 428 subjects with a mean age of 85 years, of whom 71% were women. They demonstrated comorbidity with a mean of three registered medical diagnoses, and polypharmacy with a mean of seven regularly used drugs. More than half of the sample (60%) were at risk of malnutrition and one third were at risk of developing pressure ulcers. A set of single items from the performed risk assessments was found to be important in understanding frailty and need for care. One third of the women and half of the men had anaemia. For the men, anaemia was associated with significantly higher mortality. Haemoglobin decline was also associated with higher mortality. Almost everyone (93%) had an increased fall risk and 62% had fallen during the last year. There was an association between falls during the last year and regular use of non-benzodiazepine hypnotics. In the older age group there was also an association between these drugs and serious falls the next 6 months. Dementia was previously diagnosed in 42%. However, among subjects without a dementia diagnosis, 72% were cognitively impaired (Mini Mental State Examination <24). These subjects were significantly older, did not get anti-dementia treatment and had higher levels of brain natriuretic peptide compared to the diagnosed dementia group, possibly indicating heart failure. Their risks of malnutrition and pressure ulcers were similar to the dementia group.Conclusions: Nursing home residents are generally frail. Anaemia is associated with higher mortality among men. The fall risk is generally high and use of non-benzodiazepine hypnotics is associated with a higher occurrence of falls. Cognitive impairment is undiagnosed in half of the cases and may indicate underlying heart failure. Consequently, regular medical follow-ups in this population are proposed to include blood count, drug review, and cognitive evaluation. In the case of cognitive impairment, exclusion of underlying disease such as heart failure should be considered.
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