| 1. |
- Looi, Jefferey Chee Leong, et al.
(författare)
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Shape analysis of the neostriatum in frontotemporal lobar degeneration, Alzheimer's disease, and controls
- 2010
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 51:3, s. 970-986
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Frontostriatal circuit mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD), but not Alzheimer's disease, or healthy aging. We measured the neostriatum (caudate nucleus and putamen) volume in FTLD (n=34), in comparison with controls (n=27) and Alzheimer's disease (AD, n=19) subjects. Methods: Diagnoses were based on international consensus criteria. Manual bilateral segmentation of the caudate nucleus and putamen was conducted blind to diagnosis by a single analyst, on MRI scans using a standardized protocol. Intra-cranial volume was calculated via a stereological point counting technique and was used for scaling the shape analysis. The manual segmentation binaries were analyzed using UNC Shape Analysis tools (University of North Carolina) to perform comparisons among FTLD, AD, and controls for global shape, local p-value significance maps, and mean magnitude of shape displacement. Results: Shape analysis revealed that there was significant shape difference between FTLD, AD, and controls, consistent with the predicted frontostriatal dysfunction and of significant magnitude, as measured by displacement maps. There was a lateralized difference in shape for the left caudate for FTLD compared to AD; non-specific global atrophy in AD compared to controls; while FTLD showed a more specific pattern in regions relaying fronto- and corticostriatal circuits. Conclusions: Shape analysis shows regional specificity of atrophy, manifest as shape deflation, with implications for frontostriatal and corticostriatal motoric circuits, in FTLD, AD, and controls.
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| 2. |
- Lövdén, Martin, et al.
(författare)
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The dimensionality of between-person differences in white matter microstructure in old age
- 2013
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 34:6, s. 1386-1398
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Tidskriftsartikel (refereegranskat)abstract
- Between-person differences in white matter microstructure may partly generalize across the brain and partly play out differently for distinct tracts. We used diffusion-tensor imaging and structural equation modeling to investigate this issue in a sample of 260 adults aged 60–87 years. Mean fractional anisotropy and mean diffusivity of seven white matter tracts in each hemisphere were quantified. Results showed good fit of a model positing that individual differences in white matter microstructure are structured according to tracts. A general factor, although accounting for variance in the measures, did not adequately represent the individual differences. This indicates the presence of a substantial amount of tract-specific individual differences in white matter microstructure. In addition, individual differences are to a varying degree shared between tracts, indicating that general factors also affect white matter microstructure. Age-related differences in white matter microstructure were present for all tracts. Correlations among tract factors did not generally increase as a function of age, suggesting that aging is not a process with homogenous effects on white matter microstructure across the brain. These findings highlight the need for future research to examine whether relations between white matter microstructure and diverse outcomes are specific or general. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
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| 3. |
- Damian, Marinella, et al.
(författare)
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Single-Domain Amnestic Mild Cognitive Impairment Identified by Cluster Analysis Predicts Alzheimer's Disease in the European Prospective DESCRIPA Study
- 2013
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Ingår i: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 36:1-2, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: To identify prodromal Alzheimer's disease (AD) subjects using a data-driven approach to determine cognitive profiles in mild cognitive impairment (MCI). Methods: A total of 881 MCI subjects were recruited from 20 memory clinics and followed for up to 5 years. Outcome measures included cognitive variables, conversion to AD, and biomarkers (e. g. CSF, and MRI markers). Two hierarchical cluster analyses (HCA) were performed to identify clusters of subjects with distinct cognitive profiles. The first HCA included all subjects with complete cognitive data, whereas the second one selected subjects with very mild MCI (MMSE >= 28). ANOVAs and ANCOVAs were computed to examine whether the clusters differed with regard to conversion to AD, and to AD-specific biomarkers. Results: The HCAs identified 4-cluster solutions that best reflected the sample structure. One cluster (aMCIsingle) had a significantly higher conversion rate (19%), compared to subjective cognitive impairment (SCI, p < 0.0001), and non-amnestic MCI (naMCI, p = 0.012). This cluster was the only one showing a significantly different biomarker profile (A beta(42), t-tau, APOE epsilon 4, and medial temporal atrophy), compared to SCI or naMCI. Conclusion: In subjects with mild MCI, the single-domain amnestic MCI profile was associated with the highest risk of conversion, even if memory impairment did not necessarily cross specific cut-off points. A cognitive profile characterized by isolated memory deficits may be sufficient to warrant applying prevention strategies in MCI, whether or not memory performance lies below specific z-scores. This is supported by our preliminary biomarker analyses. However, further analyses with bigger samples are needed to corroborate these findings. Copyright (C) 2013 S. Karger AG, Basel
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| 4. |
- Hooshmand, Babak, et al.
(författare)
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Vitamin D in Relation to Cognitive Impairment, Cerebrospinal Fluid Biomarkers, and Brain Volumes
- 2014
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Ingår i: 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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Tidskriftsartikel (refereegranskat)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. |
- Laukka, Erika J., et al.
(författare)
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Associations between White Matter Microstructure and Cognitive Performance in Old and Very Old Age
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Increasing age is associated with deficits in a wide range of cognitive domains as well as with structural brain changes. Recent studies using diffusion tensor imaging (DTI) have shown that microstructural integrity of white matter is associated with cognitive performance in elderly persons, especially on tests that rely on perceptual speed. We used structural equation modeling to investigate associations between white matter microstructure and cognitive functions in a population-based sample of elderly persons (age >= 60 years), free of dementia, stroke, and neurological disorders (n = 253). Participants underwent a magnetic resonance imaging scan, from which mean fractional anisotropy (FA) and mean diffusivity (MD) of seven white matter tracts were quantified. Cognitive functioning was analyzed according to performance in five task domains (perceptual speed, episodic memory, semantic memory, letter fluency, and category fluency). After controlling for age, FA and MD were exclusively related to perceptual speed. When further stratifying the sample into two age groups, the associations were reliable in the old-old (>= 78 years) only. This relationship between white matter microstructure and perceptual speed remained significant after excluding persons in a preclinical dementia phase. The observed pattern of results suggests that microstructural white matter integrity may be especially important to perceptual speed among very old adults.
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| 6. |
- Hagnelius, Nils-Olof, 1953-, et al.
(författare)
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Blood concentrations of homocysteine and methylmalonic acid among demented and non-demented Swedish elderly with and without home care services and vitamin B(12) prescriptions
- 2012
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Ingår i: Dementia and Geriatric Cognitive Disorders Extra. - Basel, Switzerland : S. Karger. - 1664-5464. ; 2:1, s. 387-399
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Total plasma homocysteine (tHcy) has been suggested as a risk factor of dementia. Our aim was to investigate potential differences in tHcy status in relation to the prescription of vitamin B(12) and dementia diagnosis. We examined whether vitamin B(12) prescriptions, a family history of dementia, or the need for home care service might be associated with tHcy values.Methods: A cross-sectional monocenter study comprising 926 consecutive subjects attending our Memory Care Unit was conducted.Results: Demented subjects being prescribed vitamin B(12) had higher serum vitamin B(12) (p = 0.025) but also higher tHcy (p < 0.001) and serum methylmalonate (p = 0.032), and lower serum folate (p < 0.001) than those who did not receive vitamin B(12) prescriptions. tHcy levels were significantly higher in non-demented subjects receiving home care service (p = 0.007). This group also had lower serum albumin (dementia: p < 0.001; non-dementia: p = 0.004). There was no difference in renal function (estimated glomerular filtration rate) in demented or non-demented subjects with or without vitamin B(12) prescriptions (dementia with/without vitamin B(12) prescription: p = 0.561; non-dementia with/without vitamin B(12) prescription: p = 0.710).Conclusion: Despite vitamin B(12) prescriptions, demented subjects had higher tHcy and methylmalonate values. The elevated metabolite values could not be explained by differences in renal function. Thus, elderly subjects on vitamin B(12) prescription appear to have unmet nutritional needs.
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| 7. |
- Ferencz, Beata, et al.
(författare)
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The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
- 2013
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Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 6087 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 x 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r(2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE epsilon 4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R-2 = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R-2 = 0.08) risk alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE epsilon 4 carriers with additional TOMM40 risk alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.
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| 8. |
- Freund-Levi, Yvonne, 1956-, et al.
(författare)
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Galantamine versus risperidone treatment of neuropsychiatric symptoms in patients with probable dementia : an open randomized trial
- 2014
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Ingår i: The American journal of geriatric psychiatry. - : Elsevier. - 1064-7481 .- 1545-7214. ; 22:4, s. 341-248
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the effects of galantamine and risperidone on neuropsychiatric symptoms in dementia (NPSD) and global function.METHODS: Using a randomized, controlled and open-blind, one-center trial at an in- and outpatient clinic at a university hospital, we studied 100 adults with probable dementia and NPSD. Participants received galantamine (N = 50, target dose 24 mg) or risperidone (N = 50, target dose 1.5 mg) for 12 weeks. The primary outcome was effects on NPSD assessed by the Neuropsychiatric Inventory (NPI). Secondary measures included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating, Clinical Global Impression, and Simpson Angus scales. All tests were performed before and after treatment.RESULTS: Outcome measures were analyzed using analysis of covariance. Ninety-one patients (67% women, mean age 79 ± 7.5 years) with initial NPI score of 51.0 (± 25.8) and MMSE of 20.1 (± 4.6) completed the trial. Both galantamine and risperidone treatments resulted in improved NPSD symptoms and were equally effective in treating several NPI domains. However, risperidone showed a significant treatment advantage in the NPI domains irritation and agitation, F(1, 97) = 5.2, p = 0.02. Galantamine treatment also ameliorated cognitive functions where MMSE scores increased 2.8 points compared with baseline (95% confidence interval: 1.96-3.52). No treatment-related severe side effects occurred.CONCLUSIONS: These results support that galantamine, with its benign safety profile, can be used as first-line treatment of NPSD symptoms, unless symptoms of irritation and agitation are prominent, where risperidone is more efficient.
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| 9. |
- 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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| 10. |
- 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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